Notes

Prophylactic Intra-Peritoneal Water drainage Right after Pancreatic Resection: An Updated Meta-Analysis.
Endocrine maintenance remedy for ladies along with low-grade serous ovarian most cancers inside the front-line environment: A deliberate assessment.
Raman spectroscopy regarding body along with urine fluid biopsies regarding ovarian most cancers diagnosis: detection regarding radiation results.
Type 4 renal tubular acidosis (RTA) is a type of metabolic acidosis characterized by hyperchloremia and hyperkalemia resulting from the reduction in and/or resistance to aldosterone. RTA can be caused by multiple different medications including angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB), potassium-sparing diuretics, and heparin. In this case, we discuss renal tubular acidosis caused by heparin use for the prevention of thromboembolic disease in COVID-19 infections.Tumor lysis syndrome (TLS) occurring after surgical resection of right atrium (RA) and inferior vena cava (IVC) tumor thrombus is a very rare but insidious condition. We report a case of hepatocellular carcinoma who developed TLS after uneventful excision of RA+IVC tumor thrombus under median sternotomy and cardiopulmonary bypass (CPB). Although the procedure was not expected to arouse massive tumor cell necrosis, post-operative course was complicated by metabolic acidosis, hypocalcemia, and progressive hyperkalemia indicative of TLS. Unfortunately, laboratory diagnosis of TLS was delayed under conditions of continuous renal replacement therapy (CRRT) for peri-operative acute renal failure. Despite all efforts, the patient died 36 hours after surgery due to lethal arrhythmia and disseminated infarction of the kidneys, spleen, and liver.Background With the modernization of biotechnology, there has been a concerted effort to create novel biomaterials to promote arthrodesis for spine surgery. The novel use of the stem cells from bone marrow aspirate (BMA) to augment spine surgery is a burgeoning field because these cells are considered to be both osteoinductive and osteogenic. We sought to review the evidence behind the use of BMAs in spinal fusions and report the results of our own case series. Methods PubMed and EMBASE databases were searched for studies that investigated the use of stem cells for spine surgery. For our own case series, the medical records of 150 consecutive patients who underwent a lumbar spinal fusion with BMA were retrospectively reviewed for adverse events (AEs) for up to two years after surgery. Results In our case series, there were no AEs identified in 49% of our patients. Of the identified AEs, 61% were unrelated to the use of BMA (e.g., UTI and heart failure), with the remaining 39% likely unrelated to its use (e.g., back pain and anemia). There was a 92.8% arthrodesis rate with the use of BMA. Conclusions We reviewed the rationale, basic science, and clinical science for BMA usage in spine surgery and concluded that BMA is safe for use in spine surgery and is associated with a high rate of arthrodesis.Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 infection commonly affects the pulmonary system, ranging from being asymptomatic to having mild upper respiratory tract infection symptoms, to having severe cases causing multi-organ failure. However, COVID-19 infection involving the gastrointestinal (GI) tract leading to pancolitis is an extremely rare complication. We present a rare case of a patient who presented with pancolitis and on testing for admission found to be positive for COVID-19. We will explore the GI tropism and the mechanism of COVID-19 infection with gastrointestinal symptoms of pancolitis.During the coronavirus disease 2019 (COVID-19) pandemic, mannequin models have been developed to mimic viral spread using fluorescent particles. These models use contraptions such as a spray gun or an exploding latex balloon to emanate a sudden acceleration of particles, simulating a "cough" reflex. No models have been developed to mimic passive aerosolization of viral particles during a cardiopulmonary arrest simulation. Our novel approach to aerosolization of simulated viral spread allows for a continuous flow of particles, which allows us to maintain components of high-fidelity team-based simulations. Our simulated model emanated GloGerm (Moab, UT) from the respiratory tract using a continuous nebulization chamber. Uniquely, the construction of our apparatus allowed for the ability to perform full, simulated cardiopulmonary resuscitation scenarios (such as chest compressions, bag-mask ventilation, and endotracheal intubation) on a high-fidelity mannequin while visualizing potential contamination spread at the conclusion of the simulation. Positive feedback from users included the ability to visualize particulate contamination after cardiopulmonary resuscitations in the context of personal protective equipment usage and roles in resuscitation (i.e. physician, respiratory therapist, nurse). Negative criticism towards the simulation included the lack of certain high-fidelity feedback markers of the mannequin (auscultating breath sounds and checking pulses) due to the construction of the particle aerosolization mechanism.Introduction Interbody spacers are necessary for achieving disc height restoration when surgical intervention is used for the treatment of severe degenerative disc disease. Minimally invasive lateral lumbar interbody fusion (MIS LLIF) is a popular surgical approach that historically uses large static interbody spacers through a lateral approach. However, static spacers have been associated with iatrogenic distraction and excessive impaction forces, which may increase the risk of subsidence and loss of lordosis, compromising stability. Expandable interbody spacers with or without adjustable lordosis may help address these concerns by maximizing segmental lordosis and aiding in sagittal balance correction. This study describes the clinical and radiographic outcomes of patients treated with expandable interbody spacers with or without adjustable lordosis, for MIS LLIF. Materials and methods This is retrospective, single-surgeon Institutional Review Board-exempt chart review was of 103 consecutive patients who has. Conclusion Indirect decompression and sagittal correction were achieved and maintained through a 24-month follow-up. Functional clinical outcomes significantly improved based on decreased VAS pain and ODI scores at 24 months. This study resulted in positive clinical and radiographic outcomes for patients who underwent MIS LLIF with expandable interbody spacers with or without adjustable lordosis.Cutaneous metastases occur in approximately 10% of oncology patients as a feature of a persistent solid tumor or the harbinger of recurrent neoplastic disease. However, they can be the presenting manifestation of an unsuspected visceral malignancy in one percent of previously cancer-free individuals. Metastatic skin lesions from breast carcinoma are diverse in their appearance. The clinical presentation of cutaneous metastases in three women with breast cancer is described and both the morphology of skin metastases caused by breast carcinoma and the conditions that are mimicked by breast cancer cutaneous metastases are reviewed. link= selleck chemicals llc Skin metastases from breast carcinoma commonly appear as firm, flesh-colored to red, smooth or ulcerated or crusted, nodules, papules, and plaques on the ipsilateral chest wall and breast. However, unique sites of breast cancer cutaneous metastases are the eyelids, inframammary folds, ipsilateral lymphedematous arm, scalp, subungual nail bed, and umbilicus; in addition, skin metastasercinoma cutaneous metastases can not only mimic other miscellaneous conditions such as erosions and ulcers, Paget's disease, and papillomatosis cutis lymphostatica but also have unusual morphology such as targetoid lesions or a sharply demarcated red infiltration of the nasal tip similar to a clown's nose. The possibility of a breast cancer cutaneous metastasis should be considered in the evaluation of a patient with breast cancer--and although less likely, in a cancer-free individual--who develops a new and/or a treatment-unresponsive cutaneous lesion. A biopsy of the skin lesion is necessary to confirm the diagnosis of breast cancer cutaneous metastasis.Loperamide, an over-the-counter antidiarrheal, works on the µ opioid receptor with minimal opioid activity if taken as directed. Recently, it has gained popularity as the "poor man's methadone" at supratherapeutic dosing. Opioid antagonism with naloxone is beneficial in reversing respiratory depression but has no effect on cardiotoxicity due to the human ether-a-go-go-related gene (hERG). We present the case of a 34-year-old female who presented for syncope after taking 48 tablets of 2 mg loperamide. On arrival, she was obtunded with variable heart block and a QTc of 560 ms. Subsequently, due to further QT prolongation from loperamide to 656 ms, she developed Torsades de Pointes requiring defibrillation at 120 J twice. Ultimately, she was discharged home with psychiatric and substance abuse outpatient follow-up. Patients and healthcare providers face new challenges with the increase in loperamide misuse due to easy access and delayed identification. It is important for clinicians to recognize and be familiar with loperamide overdose given the potential for multiorgan failure and increased mortality.Growth plate injury of the proximal humerus is rare. We herein report a traumatic growth plate injury of the proximal humerus in an elite diving athlete. A 16-year-old female diving athlete injured her left shoulder during 7.5 m platform hands-first diving practice. At the first visit, she presented with upper left shoulder tenderness and left shoulder range-of-motion limitation. There was no fracture or dislocation on X-ray and computed tomography (CT), but magnetic resonance imaging (MRI) showed a high-intensity zone in the left lateral epiphysis of the proximal humerus. We treated her conservatively by rest with sling and rehabilitation. She partially restarted diving practice five weeks post-injury and returned to competition eight weeks post-injury. Even if there is no sign of fracture or dislocation, we should consider MRI for patients who are before the age of growth plate closure.We present the case of a healthy 38-year-old male who developed parosmia following a second dose of AstraZeneca with a negative nasal swab of coronavirus disease 2019 (COVID-19) infection. The patient noted parosmia that started suddenly after one week of receiving the second dose of AstraZeneca with no association with other symptoms. The patient has still not recovered from his parosmia until the publication of this article. The olfactory disorder was confirmed using a validated questionnaire for parosmia assessment and examination by rhinoscopy. Parosmia is a rare side effect of COVID-19, and its pathophysiological mechanism is still unknown. More research in the future is needed to know the association of parosmia with COVID-19 vaccine.Hypoglossal nerve palsy is usually associated with glossopharyngeal nerve, vagus nerve, and accessory nerve palsy, and the occurrence of hypoglossal nerve palsy alone is rare. We report a case of a 41-year-old man with unilateral isolated hypoglossal nerve palsy. The patient was aware of a leftward deviation of the tongue along with pharyngeal pain. The pharyngeal pain was quickly relieved by antibiotic treatment, but the deviation of the tongue did not improve, and the patient was referred to our hospital. As a result of the medical examination, a single paralysis of the left hypoglossal nerve and mild swelling of the left lingual tonsil up to the left palatine tonsil were observed. Various tests were performed, but there were no significant abnormal findings other than a suggestion of mild tonsillitis. selleck chemicals llc We diagnosed the patient as idiopathic or tonsillitis-induced unilateral hypoglossal nerve palsy and started medical treatment with corticosteroids and methylcobalamin. The hypoglossal nerve palsy showed a tendency to improve after one month of onset and was almost cured by two months of onset.Colchicine-induced myopathy has been described in patients with chronic renal failure and patients who are using a concomitant drug like a statin. However, pure myopathy caused by colchicine has never been reported in Saudi Arabia. A 64-year-old patient received colchicine for his gout arthritis disease and developed upper and lower limb weakness. selleck chemicals llc He had a proximal weakness, and his muscle enzymes were very high. Furthermore, the needle electromyography (EMG) examination showed abundant fibrillations, myotonic discharges, and myopathic motor units. Two weeks after colchicine cessation, his weakness improved dramatically with normalization of creatine kinase (CK) and disappearance of myotonic discharges in the repeated EMG. This is the first case in Saudi Arabia that showed colchicine-induced myositis. The local clinicians' community needs to be aware of this rare side effect, as clinical suspicion is the most important diagnostic clue and the only effective treatment is the termination of colchicine.The submandibular gland is the most common major salivary gland vulnerable to sialadenitis secondary to sialolithiasis. We report a case of submandibular steinstrasse causing sialadenitis in a 45-year-old male and describe the appearances on high-resolution ultrasonography. Endoscopic-assisted excision of calculi was done. Post-operative recovery was uneventful and the patient was discharged after one week. The patient has been on follow-up for six months with no complaints of recurrence. Multiple stacked calculi within the Wharton's duct is an exceedingly rare occurrence. Steinstrasse creates a dilemma of choice for the intended surgical approach during calculi extraction from the Wharton's duct. Endoscopic guided calculi extraction may be ideal for distally placed calculi along the course of the duct. Submandibular steinstrasse can be a possibility when electrohydraulic or pneumatic techniques have been deployed.Vascular anomalies are present in the posterior circulation. In the case of this stroke patient, the posterior cerebral artery (PCA) was shown to have a fetal origin. A fetal PCA is classified as either a partial or complete fetal PCA, which can be determined by the presence of a remnant or absence of P1, the PCA segment directly arising from the terminal of the basilar artery. If absent, the PCA has arisen completely from the internal carotid artery (ICA) and is termed complete fetal PCA, or cfPCA. A partial fetal PCA, or pfPCA, is what is found when a hypoplastic segment persists. Here, we report a partial infarction of the oculomotor nucleus with ipsilateral fetal PCA in a 59-year-old female.Central pontine myelinolysis is a non-inflammatory neurologic deficit and can have a wide array of clinical features, predisposing risk factors as well as different patterns of onset along with a big difference in prognosis ranging from asymptomatic cases to encephalopathy and also mortality. Apart from the common risk factors like hyponatremia and sudden correction of electrolyte imbalances, sometimes, the least prevalent risk factors such as pregnancy seem to link with the central pontine myelinolysis. Mostly its onset is sudden after the inciting factors. However, it is also likely to have cases of central pontine myelinolysis with gradual onset of clinical features. The purpose of the case report is to highlight the link between pregnancy and central pontine myelinolysis. The slow onset of clinical features in pregnancy-linked central pontine myelinolysis can also be considered. The patient in the case report presented with gradual onset clinical features of osmotic demyelination syndrome during the last months of pregnancy and immediately postpartum. All the possible predisposing risk factors for central pontine myelinolysis were ruled out through history, physical examination, and relevant investigations. The case study of the patient hypothesized that (1) pregnancy should be considered as a risk factor for central pontine myelinolysis in pregnant and postpartum patients presenting with clinical features of the disease, (2) clinical features of central pontine myelinolysis in pregnancy can have a more gradual onset of symptoms compared to other causes of central pontine myelinolysis. Although, this case report signifies a relationship between pregnancy and osmotic demyelination syndrome. However, further studies should be done to develop a causal relationship and preventive measures for the condition.Snakebite is a neglected tropical disease, which is very common in the Indian subcontinent. The severity of respiratory muscle paralysis and the delay in recovery depend upon the dose of the venom injected, the severity of the venom, the species of the snake, the duration of presentation to the hospital, and the time and dose of administration of anti-snake venom (ASV). The reasons for this delayed neuromuscular recovery still remain an enigma. We highlight such a case of a young adult who had delayed neuromuscular recovery and prolonged ventilatory support following a neurotoxic snakebite.The coronavirus disease 2019 (COVID-19) pandemic has caused the world to operate uncharacteristically for almost the last two years. Governments across the globe have taken different control measures to eradicate it. link2 The Oxford COVID-19 Government Response Tracker (OxCGRT) provides open access data for different countries on 20 control measures, including numerous aggregated indices. This paper employs the modified Susceptible-Exposed-Infectious-Recovered (SEIR) epidemiology model to study the COVID-19 pandemic in Saudi Arabia. The modification has been achieved by including control measures and the infectiousness of exposed compartment. A hybrid approach has been used to estimate and incorporate control measures. Initially, a composite control measure has been derived from OxCGRT data to make an attempt to fit the COVID-19 pattern in Saudi Arabia. The derived model has proven to be satisfactory through statistical tests. Nonetheless, the model patterns do not resemble the reported patterns more closely. Hence, a second heuristic approach has been utilized to devise effective control measures from the reported pattern of COVID-19 from the Saudi government agency. A satisfactory model was derived utilizing this approach with successful validation through statistical tests. Also, the model patterns more closely resemble the reported patterns of COVID-19 cases. This hybrid approach proves more robust and ensures the validity of model parameters better. The R naught (R0) value with the current control measures has varied from 0.515 to 1.892, with a mean value of 1.119, and is presently less than 1. The threshold herd immunity, in the absence of any control measure, is estimated to be 47.12% with an R0 value of 1.89 and would end up infecting 76.32% of the population. The scenario analysis with gradual partial and complete relaxations up to December 31, 2021, shows that the peaks are likely to occur in 2022; therefore, Saudi Arabia must continue to inoculate its population to eradicate COVID-19.Despite the decline in COVID-19 cases, the potential threat of multisystem inflammatory syndrome (MIS) - a hyperinflammatory response following acute SARS-CoV-2 infection - looms large. Although initially described in children, it is being increasingly reported in adults. In dengue endemic regions, MIS is likely to cause diagnostic dilemma with dengue due to overlapping clinical and laboratory features. We describe a young male with fever, gastrointestinal symptoms, a transient rash, thrombocytopenia, and positive dengue NS1 antigen test. Early onset of thrombocytopenia, significant gastrointestinal symptoms and protracted fever were atypical, raising suspicion of MIS-A in view of a recovery from a recent SARS-CoV-2 infection. However, absence of neurologic and cardiac manifestations, stable hemodynamics, absence of mucosal involvement and negative inflammatory markers helped in managing the patient conservatively as dengue. This case highlights diagnostic challenges faced by clinicians treating suspected dengue in the face of increasing recognition of MIS and need for systematic research to establish diagnostic criteria for MIS-A.Both SARS-CoV-2 and SARS coronaviruses (CoVs) are members of the subgenus Sarbecovirus. To understand the origin of SARS-CoV-2, sequences for the spike and nucleocapsid proteins from sarbecoviruses were analyzed to identify molecular markers consisting of conserved inserts or deletions (termed CSIs) that are specific for either a particular clade of Sarbecovirus or are commonly shared by two or more clades of these viruses. Three novel CSIs in the N-terminal domain (NTD) of the spike protein S1-subunit (S1-NTD) are uniquely shared by SARS-CoV-2, Bat-CoV-RaTG13 and most pangolin CoVs (SARS-CoV-2r clade). Three other sarbecoviruses viz. bat-CoVZXC21, -CoVZC45 and -PrC31 (forming CoVZC/PrC31 clade), and a pangolin-CoV_MP789 also contain related CSIs in the same positions. In contrast to the S1-NTD, both SARS and SARS-CoV-2r viruses contain two large CSIs in the S1-C-terminal domain (S1-CTD) that are absent in the CoVZC/PrC31 clade. One of these CSIs, consisting of a 12 aa insert, is also present in the RShSTT clCoV-2. Several other CSIs reported here are specific for other clusters of sarbecoviruses including a clade consisting of bat-SARS-CoVs (BM48-31/BGR/2008 and SARS_BtKY72). Structural mapping studies show that the identified CSIs form distinct loops/patches on the surface of the spike protein. It is hypothesized that these novel loops/patches on the spike protein, through their interactions with other host components, should play important roles in the biology/pathology of SARS-CoV-2 virus. Lastly, the CSIs specific for different clades of sarbecoviruses including SARS-CoV-2r clade provide novel means for the identification of these viruses and other potential applications.Aerosol particles are one of the main routes of transmission of COVID-19. Mobile air purifiers are used to reduce the risk of infection indoors. We focus on an air purifier that generates a defined volumetric air flow through a highly efficient filter material. We investigate the transport of aerosol particles from an infected dummy equipped with an aerosol generator to receiving thermal dummies. For analysis, we use up to 12 particle sensors to monitor the particle concentration with high spatial resolution. Based on the measurement data, a computational fluid dynamics (CFD) model is set up and validated. The experimental and numerical methods are used to investigate how the risk of infection suggested by the particle exposure in an exemplary lecture hall can be reduced by a clever choice of orientation of the air purifier. It turns out that obstructing the outlet stream of the air purifier may be particularly advantageous. The particle concentration at the head height deviates by 13% for variations of the location and orientation. At an air change per hour of 5, the cumulated PM1 mass at the head level was reduced by 75%, independently of the location of the infected dummy, compared to the "natural decay" case, showing that filtration is an effective means of reducing aerosol particle concentrations. Finally, CFD simulation was used to monitor the particle fates. The steady simulation results fit quite well with the experimental findings and provide additional information about the particle path and for assessing the comfort level due to air flow.Reactive carbenes generated from diazo compounds are key intermediates for a range of organic reactions to afford synthetically useful organic compounds. The majority of these reactions have been carried out using transition metal catalysts. However, the formation of carbene intermediates using main group elements has not been widely investigated for synthetic purposes. Recent studies have demonstrated that triarylboranes can be used for the in situ generation of reactive carbene intermediates in both stoichiometric and catalytic reactions. These new reactivities of triarylboranes have gained significant attention in synthetic chemistry particularly in catalytic studies. The range of organic compounds that have been synthesized through these reactions are important as pharmaceuticals or agrochemicals. In this perspective, we highlight the recent progress and ongoing challenges of carbene transfer reactions generated from their corresponding diazo precursors using triarylboranes as catalysts. We also highlight the stoichiometric use of triarylboranes in which the boranes not only activate the diazo functionality to afford a carbene intermediate but also actively participate in the reactions as a reagent. The different mechanisms for activation and carbene transfer are described along with the mechanistic and computational studies that have aided the elucidation of these reaction pathways. Potential opportunities for the use of boranes as a catalyst toward different carbene transfer reactions and their future prospects are discussed.The presence of defects and chemical dopants in metal-free carbon materials plays an important role in the electrocatalysis of the oxygen reduction reaction (ORR). The precise control and design of defects and dopants in carbon electrodes will allow the fundamental understanding of activity-structure correlations for tailoring catalytic performance of carbon-based, most particularly graphene-based, electrode materials. Herein, we adopted monolayer graphene - a model carbon-based electrode - for systematical introduction of nitrogen and oxygen dopants, together with vacancy defects, and studied their roles in catalyzing ORR. Compared to pristine graphene, nitrogen doping exhibited a limited effect on ORR activity. In contrast, nitrogen doping in graphene predoped with vacancy defects or oxygen enhanced the activities at 0.4 V vs the reversible hydrogen electrode (RHE) by 1.2 and 2.0 times, respectively. The optimal activity was achieved for nitrogen doping in graphene functionalized with oxygenated defects, 12.8 times more than nitrogen-doped and 7.7 times more than pristine graphene. More importantly, oxygenated defects are highly related to the 4e- pathway instead of nitrogen dopants. This work indicates a non-negligible contribution of oxygen and especially oxygenated vacancy defects for the catalytic activity of nitrogen-doped graphene.The present research provides a study of carbon-supported intermetallic Pt-alloy electrocatalysts and assesses their stability against metal dissolution in relation to the operating temperature and the potential window using two advanced electrochemical methodologies (i) the in-house designed high-temperature disk electrode (HT-DE) methodology as well as (ii) a modification of the electrochemical flow cell coupled to an inductively coupled plasma mass spectrometer (EFC-ICP-MS) methodology, allowing for highly sensitive time- and potential-resolved measurements of metal dissolution. While the rate of carbon corrosion follows the Arrhenius law and increases exponentially with temperature, the findings of the present study contradict the generally accepted hypothesis that the kinetics of Pt and subsequently the less noble metal dissolution are supposed to be for the most part unaffected by temperature. On the contrary, clear evidence is presented that in addition to the importance of the voltage/potential window, the temperature is one of the most critical parameters governing the stability of Pt and thus, in the case of Pt-alloy electrocatalysts, also the ability of the nanoparticles (NPs) to retain the less noble metal. Lastly, but also very importantly, results indicate that the rate of Pt redeposition significantly increases with temperature, which has been the main reason why mechanistic interpretation of the temperature-dependent kinetics related to the stability of Pt remained highly speculative until now.Transition-metal- and nitrogen-codoped carbide-derived carbon/carbon nanotube composites (M-N-CDC/CNT) have been prepared, characterized, and used as cathode catalysts in anion-exchange membrane fuel cells (AEMFCs). As transition metals, cobalt, iron, and a combination of both have been investigated. Metal and nitrogen are doped through a simple high-temperature pyrolysis technique with 1,10-phenanthroline as the N precursor. The physicochemical characterization shows the success of metal and nitrogen doping as well as very similar morphologies and textural properties of all three composite materials. The initial assessment of the oxygen reduction reaction (ORR) activity, employing the rotating ring-disk electrode method, indicates that the M-N-CDC/CNT catalysts exhibit a very good electrocatalytic performance in alkaline media. We find that the formation of HO2 - species in the ORR catalysts depends on the specific metal composition (Co, Fe, or CoFe). All three materials show excellent stability with a negligible decline in their performance after 10000 consecutive potential cycles. The very good performance of the M-N-CDC/CNT catalyst materials is attributed to the presence of M-N x and pyridinic-N moieties as well as both micro- and mesoporous structures. Finally, the catalysts exhibit excellent performance in in situ tests in H2/O2 AEMFCs, with the CoFe-N-CDC/CNT reaching a current density close to 500 mA cm-2 at 0.75 V and a peak power density (P max) exceeding 1 W cm-2. Additional tests show that P max reaches 0.8 W cm-2 in an H2/CO2-free air system and that the CoFe-N-CDC/CNT material exhibits good stability under both AEMFC operating conditions.Suppression of cellular O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) can repress proliferation and migration of various cancer cells, which opens a new avenue for cancer therapy. Based on the regulation of insulin gene transcription, we designed a cell-based fluorescent reporter capable of sensing cellular O-GlcNAcylation in HEK293T cells. The fluorescent reporter mainly consists of a reporter (green fluorescent protein (GFP)), an internal reference (red fluorescent protein), and an operator (neuronal differentiation 1), which serves as a "sweet switch" to control GFP expression in response to cellular O-GlcNAcylation changes. The fluorescent reporter can efficiently sense reduced levels of cellular O-GlcNAcylation in several cell lines. Using the fluorescent reporter, we screened 120 natural products and obtained one compound, sesamin, which could markedly inhibit protein O-GlcNAcylation in HeLa and human colorectal carcinoma-116 cells and repress their migration in vitro. Altogether, the present study demonstrated the development of a novel strategy for anti-tumor drug screening, as well as for conducting gene transcription studies.Non-small cell lung cancer (NSCLC) is often characterized by an underlying mutation in the epidermal growth factor receptor (EGFR), contributing to aggressive metastatic disease. Methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate (CDODA-Me), a glycyrrhetinic acid derivative, reportedly improves the therapeutic response to erlotinib (ERL), an EGFR tyrosine kinase inhibitor. In the present study, we performed a series of studies to demonstrate the efficacy of CDODA-Me (2 μM) in sensitizing HCC827R (ERL-resistant) cells to ERL. Herein, we first established the selectivity of ERL-induced drug resistance in the HCC827R cells, which was sensitized when ERL was combined with CDODA-Me (2 μM), shifting the IC50 from 23.48 μM to 5.46 μM. Subsequently, whole transcriptomic microarray expression data demonstrated that the combination of ERL + CDODA-Me elicited 210 downregulated genes (0.44% of the whole transcriptome (WT)) and 174 upregulated genes (0.36% of the WT), of which approximately 80% were unique to the ERL + CDODA-Me group. Synergistic effects centered on losses to cell cycle progression transcripts, a reduction of minichromosome maintenance complex components (MCM2-7), all key components of the Cdc45·MCM2-7GINS (CMG) complex, and replicative helicases; these effects were tantamount to the upregulation of processes associated with the nuclear factor erythroid 2 like 2 translational response to oxidative stress, including sulfiredoxin 1, heme oxygenase 1, and stress-induced growth inhibitor 1. Collectively, these findings indicate that the synergistic therapeutic effects of ERL + CDODA-Me on resistant NSCLC cells are mediated via the inhibition of mitosis and induction of oxidative stress.Unsymmetrical bisacridines (UAs) are a novel potent class of antitumor-active therapeutics. A significant route of phase II drug metabolism is conjugation with glutathione (GSH), which can be non-enzymatic and/or catalyzed by GSH-dependent enzymes. The aim of this work was to investigate the GSH-mediated metabolic pathway of a representative UA, C-2028. GSH-supplemented incubations of C-2028 with rat, but not with human, liver cytosol led to the formation of a single GSH-related metabolite. Interestingly, it was also revealed with rat liver microsomes. Its formation was NADPH-independent and was not inhibited by co-incubation with the cytochrome P450 (CYP450) inhibitor 1-aminobenzotriazole. Therefore, the direct conjugation pathway occurred without the prior CYP450-catalyzed bioactivation of the substrate. In turn, incubations of C-2028 and GSH with human recombinant glutathione S-transferase (GST) P1-1 or with heat-/ethacrynic acid-inactivated liver cytosolic enzymes resulted in the presence or lack of GSH conjugated form, respectively. These findings proved the necessary participation of GST in the initial activation of the GSH thiol group to enable a nucleophilic attack on the substrate molecule. Another C-2028-GSH S-conjugate was also formed during non-enzymatic reaction. Both GSH S-conjugates were characterized by combined liquid chromatography/tandem mass spectrometry. Mechanisms for their formation were proposed. The ability of C-2028 to GST-mediated and/or direct GSH conjugation is suspected to be clinically important. This may affect the patient's drug clearance due to GST activity, loss of GSH, or the interactions with GSH-conjugated drugs. Moreover, GST-mediated depletion of cellular GSH may increase tumor cell exposure to reactive products of UA metabolic transformations.Shengmai Yin (SMY) is a Chinese herbal decoction that effectively alleviates the side effects of radiotherapy in various cancers and helps achieve radiotherapy's clinical efficacy. In this study, we explored the interaction mechanism among SMY, DNA methylation, and nasopharyngeal carcinoma (NPC). We identified differences in DNA methylation levels in NPC CNE-2 cells and its radioresistant cells (CNE-2R) using the methylated DNA immunoprecipitation array and found that CNE-2R cells showed genome-wide changes in methylation status towards a state of hypomethylation. SMY may restore its original DNA methylation status, and thus, enhance radiosensitivity. Furthermore, we confirmed that the differential gene Tenascin-C (TNC) was overexpressed in CNE-2R cells and that SMY downregulated TNC expression. This downregulation of TNC inhibited NPC cell radiation resistance, migration, and invasion. Furthermore, we found that TNC was hypomethylated in CNE-2R cells and partially restored to a hypermethylated state after SMY intervention. DNA methyltransferases 3a may be the key protein in DNA methylation of TNC.Diarrhea is a prevalent gastrointestinal problem associated with fatal implications. It is a huge public health concern that requires better alternatives to current drugs. This study investigated the mechanisms involved in the antidiarrheal activity of Anacardium occidentale (Ao) stem bark extract, a plant commonly used in the management of diarrhea in Nigeria. Methanolic stem bark extract of the plant was partitioned into three fractions hexane fraction, ethyl acetate fraction (AoEF) and methanol fraction. In vitro studies on the effect of these fractions on guinea pig ileum (GPI) strips, as well as the modulatory effect of AoEF on standard agonists- and antagonists-induced GPI contraction and relaxation, revealed AoEF as the most active fraction. In vivo studies to assess the effect of AoEF on the dopaminergic, muscarinic, and serotonergic pathways were carried out using gastric emptying (GE) and gastrointestinal transit (GT) as experimental end points. AoEF was subjected to GC-MS analysis, while the identified compounds were docked with the muscarinic acetylcholine receptor M3 (CHRM3) using AutodockVina. Results indicated that AoEF inhibited GE and GT via inhibition of CHRM3. In addition, GC-MS analysis revealed the presence of 24 compounds in AoEF, while docking indicated that octadecanoic acid 2-(2-hydroxylethoxy) ethyl ester exhibited the highest binding affinity to CHRM3. This study indicated that the antidiarrheal activity of Ao is through its antimotility effect via the inhibition of the muscarinic pathway. And since none of the identified compounds exhibited higher binding affinity to CHRM3 relative to loperamide, the antimotility activity of these phytoconstituents may be via synergism.There is an urgent need to elucidate the pathogenesis of myocardial ischemia (MI) and potential drug treatments. Here, the anti-MI mechanism and material basis of Ginkgo biloba L. extract (GBE) were studied from the perspective of energy metabolism flux regulation. Metabolic flux analysis (MFA) was performed to investigate energy metabolism flux disorder and the regulatory nodes of GBE components in isoproterenol (ISO)-induced ischemia-like cardiomyocytes. It showed that [U-13C] glucose derived m+2 isotopologues from the upstream tricarboxylic acid (TCA) cycle metabolites were markedly accumulated in ISO-injured cardiomyocytes, but the opposite was seen for the downstream metabolites, while their total cellular concentrations were increased. This indicates a blockage of carbon flow from glycolysis and enhanced anaplerosis from other carbon sources. A Seahorse test was used to screen for GBE components with regulatory effects on mitochondrial aerobic respiratory dysfunction. It showed that bilobalide protected against impaired mitochondrial aerobic respiration. MFA also showed that bilobalide significantly modulated the TCA cycle flux, reduced abnormal metabolite accumulation, and balanced the demand of different carbon sources. Western blotting and PCR analysis showed that bilobalide decreased the enhanced expression of key metabolic enzymes in injured cells. link2 Bilobalide's efficacy was verified by in vivo experiments in rats. This is the first report to show that bilobalide, the active ingredient of GBE, protects against MI by rescuing impaired TCA cycle flux. link3 This provides a new mechanism and potential drug treatment for MI. It also shows the potential of MFA/Seahorse combination as a powerful strategy for pharmacological research on herbal medicine.P450 fatty acid decarboxylase OleT from Staphylococcus aureus (OleTSA) is a novel cytochrome P450 enzyme that catalyzes the oxidative decarboxylation of fatty acids to yield primarily terminal alkenes and CO2 or minor α- and β-hydroxylated fatty acids as side-products. In this work, the interactions between a series of cycloalkyl phosphorus heterocycles (CPHs) and OleTSA were investigated in detail by fluorescence titration experiment, ultraviolet-visible (UV-vis) and 31P NMR spectroscopies. Fluorescence titration experiment results clearly showed that a dynamic quenching occurred when CPH-6, a representative CPHs, interacted with OleTSA with a binding constant value of 15.2 × 104 M-1 at 293 K. The thermodynamic parameters (ΔH, ΔS and ΔG) showed that the hydrogen bond and van der Waals force played major roles in the interaction between OleTSA and CPHs. The UV-vis and 31P NMR studies indicated the penetration of CPH-6 into the interior environment of OleTSA, which greatly affects the enzymatic activity of OleTSA. Therefore, our study revealed an effective way to use phosphorus heterocyclic compounds to modulate the activity of cytochrome P450 enzymes.Enantioseparation of three β-blockers, i.e., atenolol, metoprolol and propranolol, was studied on amylose tris(3-chloro-5-methylphenylcarbamate) immobilized chiral stationary phase using supercritical fluid chromatography (SFC). The effect of organic modifiers (methanol, isopropanol and their mixture), column temperature and back pressure on chiral separation of β-blockers was evaluated. Optimum chromatographic separation with respect to resolution, retention, and analysis time was achieved using a mixture of CO2 and 0.1% isopropyl amine in isopropanol methanol (5050, V/V), in 7525 (V/V) ratio. Under the optimized conditions, the resolution factors (R s) and separation factors (α) were greater than 3.0 and 1.5, respectively. Further, with increase in temperature (25-45 °C) and pressure (100-150 bars) there was corresponding decrease in retention factors (k), α and R s. However, a reverse trend (α and R s) was observed for atenolol with increase in temperature. The thermodynamic data from van't Hoff plots revealed that the enantioseparation was enthalpy driven for metoprolol and propranolol while entropy driven for atenolol. To understand the mechanism of chiral recognition and the elution behavior of the enantiomers, molecular docking studies were performed. The binding energies obtained from simulation studies were in good agreement with the elution order found experimentally and also with the free energy values. The method was validated in the concentration range of 0.5-10 μg/mL for all the enantiomers. The limit of detection and limit of quantitation ranged from 0.126 to 0.137 μg/mL and 0.376-0.414 μg/mL, respectively. The method was used successfully to analyze these drugs in pharmaceutical preparations.In this study, we developed a novel on-line solid phase extraction (SPE)-ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS)-based analytical method for simultaneously quantifying 12 illicit drugs and metabolites (methamphetamine, amphetamine, morphine, codeine, 6-monoacetylmorphine, benzoylecgonine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, cocaine, ketamine, norketamine, and methcathinone) and cotinine (COT) in wastewater samples. The analysis was performed by loading 2 mL of the sample onto an Oasis hydrophilic-lipophilic balance cartridge and using a cleanup step (5% methanol) to eliminate interference with a total run time of 13 min. The isotope-labeled internal standard method was used to quantify the target substances and correct for unavoidable losses and matrix effects during the on-line SPE process. Typical analytical characteristics used for method validation were sensitivity, linearity, precision, repeatability, recovery, and matrix effects. The limit of detection (LOD) and limit of quantification (LOQ) of each target were set at 0.20 ng/L and 0.50 ng/L, respectively. The linearity was between 0.5 ng/L and 250 ng/L, except for that of COT. The intra- and inter-day precisions were less then 10.45% and 25.64%, respectively, and the relative recovery ranged from 83.74% to 162.26%. The method was used to analyze various wastewater samples from 33 cities in China, and the results were compared with the experimental results of identical samples analyzed using off-line SPE. The difference rate was between 19.91% and -20.44%, and the error range could be considered acceptable. These findings showed that on-line SPE is a suitable alternative to off-line SPE for the analysis of illicit drugs in samples.Inhaled antibiotics such as colistin and ciprofloxacin are increasingly used to treat bacterial lung infections in cystic fibrosis patients. In this study, we established and validated a new HPLC-MS/MS method that could simultaneously detect drug concentrations of ciprofloxacin, colistin and ivacaftor in rat plasma, human epithelial cell lysate, cell culture medium, and drug transport media. An aliquot of 200 μL drug-containing rat plasma or cell culture medium was treated with 600 μL of extraction solution (acetonitrile containing 0.1% formic acid and 0.2% trifluoroacetic acid (TFA)). The addition of 0.2% TFA helped to break the drug-protein bonds. Moreover, the addition of 0.1% formic acid to the transport medium and cell lysate samples could significantly improve the response and reproducibility. After vortexing and centrifuging, the sample components were analyzed by HPLC-MS/MS. The multiple reaction monitoring mode was used to detect the following transitions 585.5-101.1 (colistin A), 578.5-101.1 (colistin B), 393.2-337.2 (ivacaftor), 332.2-314.2 (ciprofloxacin), 602.3-101.1 (polymyxin B1 as internal standard (IS)) and 595.4-101.1 (polymyxin B2 as IS). The running time of a single sample was only 6 min, making this a time-efficient method. Linear correlations were found for colistin A at 0.029-5.82 μg/mL, colistin B at 0.016-3.14 μg/mL, ivacaftor at 0.05-10.0 μg/mL, and ciprofloxacin at 0.043-8.58 μg/mL. Accuracy, precision, and stability of the method were within the acceptable range. This method would be highly useful for research on cytotoxicity, animal pharmacokinetics, and in vitro drug delivery.Ensuring the removal of host cell proteins (HCPs) during downstream processing of recombinant proteins such as monoclonal antibodies (mAbs) remains a challenge. Since residual HCPs might affect product stability or safety, constant monitoring is required to demonstrate their removal to be below the regulatory accepted level of 100 ng/mg. link3 The current standard analytical approach for this procedure is based on ELISA; however, this approach only measures the overall HCP content. Therefore, the use of orthogonal methods, such as liquid chromatography-mass spectrometry (LC-MS), has been established, as it facilitates the quantitation of total HCPs as well as the identification and quantitation of the individual HCPs present. In the present study, a workflow for HCP detection and quantitation using an automated magnetic bead-based sample preparation, in combination with a data-independent acquisition (DIA) LC-MS analysis, was established. Employing the same instrumental setup commonly used for peptide mapping analysis of mAbs allows for its quick and easy implementation into pre-existing workflows, avoiding the need for dedicated instrumentation or personnel. Thereby, quantitation of HCPs over a broad dynamic range was enabled to allow monitoring of problematic HCPs or to track changes upon altered bioprocessing conditions.Xiaoer-Feire-Kechuan (XFK) is an 11-herb Chinese medicine formula to treat cough and pulmonary inflammation. The complicated composition rendered its chemical analysis and effective-component elucidation. In this study, we combined quantitative analysis and bioactivity test to reveal the anti-inflammatory constituents of XFK. First, UPLC-DAD and UHPLC/Q-Orbitrap-MS methods were established and validated to quantify 35 analytes (covering 9 out of 11 herbs) in different XFK formulations. Parallel reaction monitoring mode built in Q-Orbitrap-MS was used to improve the sensitivity and selectivity. Then, anti-inflammatory activities of the 35 analytes were analyzed using in vitro COX-2 inhibition assay. Finally, major analytes forsythosides H, I, A (8-10), and baicalin (15) (total contents varied from 21.79 to 91.20 mg/dose in different formulations) with significant activities (inhibitory rate ≥ 80%) were proposed as the anti-inflammatory constituents of XFK. The present study provided an effective strategy to discover effective constituents of multi-herb formulas.The Lianhua Qingwen (LHQW) capsule is a popular traditional Chinese medicine for the treatment of viral respiratory diseases. In particular, it has been recently prescribed to treat infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, due to its complex composition, little attention has been directed toward the analysis of chemical constituents present in the LHQW capsule. This study presents a reliable and comprehensive approach to characterizing the chemical constituents present in LHQW by high-performance liquid chromatography-Q Exactive-Orbitrap mass spectrometry (HPLC-Q Exactive-Orbitrap-MS) coupled with gas chromatography-mass spectrometry (GC-MS). An automated library alignment method with a high mass accuracy (within 5 ppm) was used for the rapid identification of compounds. A total of 104 compounds, consisting of alkaloids, flavonoids, phenols, phenolic acids, phenylpropanoids, quinones, terpenoids, and other phytochemicals, were successfully characterized. In addition, the fragmentation pathways and characteristic fragments of some representative compounds were elucidated. GC-MS analysis was conducted to characterize the volatile compounds present in LHQW. In total, 17 compounds were putatively characterized by comparing the acquired data with that from the NIST library. The major constituent was menthol, and all the other compounds were terpenoids. This is the first comprehensive report on the identification of the major chemical constituents present in the LHQW capsule by HPLC-Q Exactive-Orbitrap-MS, coupled with GC-MS, and the results of this study can be used for the quality control and standardization of LHQW capsules.An innovative, ternary nanocomposite composed of overoxidized poly(3,4-ethylenedioxythiophene) (OPEDOT), gold nanoparticles (AuNPs), and electrochemically reduced graphene oxide (ERGO) was prepared on a glassy carbon electrode (GCE) (OPEDOT-AuNPs-ERGO/GCE) through homogeneous chemical reactions and heterogeneous electrochemical methods. The morphology, composition, and structure of this nanocomposite were characterized by transmission electron microscopy, scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The electrochemical properties of the OPEDOT-AuNPs-ERGO/GCE were investigated by cyclic voltammetry using potassium ferricyanide and hexaammineruthenium(III) chloride redox probe systems. This modified electrode shows excellent electro-catalytic activity for dopamine (DA) and uric acid (UA) under physiological pH conditions, but inhibits the oxidation of ascorbic acid (AA). Linear voltammetric responses were obtained when DA concentrations of approximately 4.0-100 μM and UA concentrations of approximately 20-100 μM were used. The detection limits (S/N=3) for DA and UA were 1.0 and 5.0 μM, respectively, under physiological conditions and in the presence of 1.0 mM of AA. This developed method was applied to the simultaneous detection of DA and UA in human urine, where satisfactory recoveries from 96.7% to 105.0% were observed. This work demonstrates that the developed OPEDOT-AuNPs-ERGO ternary nanocomposite, with its excellent ion-selectivity and electro-catalytic activity, is a promising candidate for the simultaneous detection of DA and UA in the presence of AA in physiological and pathological studies.[This corrects the article on p. 18 in vol. 23, PMID 32322431.].The aim of this study was to report on the improvement of shoulder pain resulting from disorders of the rotator cuff such as impingement syndrome and adhesive capsulitis, by manual acupuncture (MA) and pharmacopuncture (PA) following origin/insertion technique (OIT) of applied kinesiology (AK). Two patients were treated with MA and PA after OIT on shoulder muscles. The Numerical Rating Scale and the assessment of the Japanese Orthopedic Association scores were used to assess the pain, and ultrasound images were taken to compare treatment outcome. This study showed that MA and PA following OIT may be an effective treatment for impingement syndrome and adhesive capsulitis.
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