Notes

Cadmium-induced hormesis impact throughout medicinal herbal products improves the performance involving safe and sound consumption regarding low cadmium-contaminated farmland garden soil.
The cyclofenil-derived dimer with C4 spacer (15b) showed the highest binding affinity to ERα (RBA = 79.2%) and downregulated the ER content in MCF-7 cells with an efficiency of 38% at 1 μM. This multicenter phase Ib study aimed to establish a recommended phase II dose for durvalumab (Du) ± tremelimumab (Tr) in combination with standard platinum-doublet chemotherapy. Eligible patients were enrolled into one of six dose levels (DL) of Du ± Tr which included concomitant treatment with standard platinum-doublet regimens; (pemetrexed, gemcitabine, etoposide, (each with cisplatin or carboplatin) or nab-paclitaxel (with carboplatin)). Dose escalation was according to a Rolling Six type design. learn more Both weight-based and fixed dosing of Du and Tr were explored. Du was continued until progression. Tr dosing was finite (up to 6 doses) with increasing dose and/or frequency by DL. 136 patients were enrolled. The majority of drug-related adverse events (AEs) were ≤ grade 2 and attributable to chemotherapy. AEs considered related to immunotherapy were mainly ≤ grade 2; the most frequent (occurring ≥10 %) were colitis/diarrhea, skin, and thyroid dysfunction. Seven patients had DLTs including pneumonitis, myocarditis, diarrhea, encephalitis, motor neuropathy, and enterocolitis. There were 2 treatment-related deaths. Tr and Du exposures did not appear affected by chemotherapy. Among the 73 non-small cell lung cancer (NSCLC) patients treated, the objective response rate was 51 % (95 %CI = 38.7-62.6 %) with a median progression-free and overall survival of 6.5 months (95 % CI = 5.5-9.4 months) and 19.8 months (95 % CI = 14.8 months - not yet reached) respectively. Anti-tumour activity was observed across PD-L1 subtypes. Du 1500 mg q3w and Tr 75 mg q3wx5 can be safely combined with platinum-doublet chemotherapy. Efficacy among NSCLC patients appears comparable to results from other immunotherapy and chemotherapy combination trials. NCT02537418. BACKGROUND 7-Hydroxycoumarin (7-HC), also known as umbelliferon, is commonly found in Chinese herbs (e.g. Eucommiae Cortex, Prunellae Spica, Radix Angelicae Biseratae). Previous laboratory studies have indicated that 7-HC has anti-inflammatory, anti-oxidative, and anti-tumor effects. Cisplatin is a widely used chemotherapeutic agent for cancer. link2 Nephrotoxicity is one of the limiting side effects of cisplatin use. PURPOSE This study aimed to evaluate the renoprotective effect of 7-HC in a cisplatin-induced acute kidney injury (AKI) mouse model. METHODS AKI was induced in male C57BL/6 mice (aged 6-8 weeks) by a single intraperitoneal injection of cisplatin at 20 mg/kg. The mice received 7-HC at 30, 60, and 90 mg/kg intraperitoneally before or after cisplatin administration. Renal function, necroptosis, and cell proliferation were measured. Mechanisms underlying the reno-protective effect of 7-HC were explored in renal tubular epithelial cells treated with or without cisplatin. link3 RESULTS In-vivo experiments showed apeutic agent for AKI. Several studies have focused on the antimicrobial effects of cerium oxide nanoparticles (CeO2-NP) but few have focused on their effects on bacteria under initial biofilm formation conditions. Streptococcus mutans is a prolific biofilm former contributing to dental caries in the presence of fermentable carbohydrates and is a recognized target for therapeutic intervention. CeO2-NP derived solely from Ce(IV) salt hydrolysis were found to reduce adherent bacteria by approximately 40% while commercial dispersions of "bare" CeO2-NP (e.g., 3 nm, 10-20 nm, 30 nm diameter) and Ce(NO3)3·6H2O were either inactive or observed to slightly increase biofilm formation under similar in vitro conditions. Planktonic growth and dispersal assays support a non-bactericidal mode of biofilm inhibition active in the initial phases of S. mutans biofilm production. Human cell proliferation assays suggest only minor effects of hydrolyzed Ce(IV) salts on cellular metabolism at concentrations up to 1 mM Ce, with less observed toxicity compared to equimolar concentrations of AgNO3. The results presented herein have implications in clinical dentistry. The transdermal route for the delivery of therapeutic agents to the inner skin tissues for non-invasive photodynamic therapy; though constitutes a desired modality for treating skin cancer, the success has been limited due to the insurmountable nature of the stratum corneum (SC). In this context, for the first time we report the localization of photosensitizer-conjugated upconversion (UC) particles to the deeper dermal region by overcoming SC through an oleogel-mediated transport mechanism for NIR-induced photodynamic production of reactive oxygen species (ROS). We developed soybean oil and stearic acid based oleogels by incorporating photoluminescent white light emitting NaYF4 (WEN) upconversion (UC) particles conjugated with Rose Bengal (RB), termed as WEN-RB-G. Similarly, we fabricated another type of oleogel by incorporating Li+ doped WEN based UC particles (RB conjugated), with 10 times more photoluminescence intensity, termed as LiWEN-RB-G. Based on the skin permeation enhancing effect of the constituents of the oleogels, we demonstrated the permeation of these two types of conjugated particles in microgram scale through the full thickness of the pig ear skin model within 48 h. The localization of the conjugated particles throughout the skin tissue including dermal and epidermal region was confirmed by confocal microscopy. We also conducted a comparative assessment on WEN-RB-G and LiWEN-RB-G for the suitability of ROS generation and bioimaging under NIR activation. The 'proof of principle' concept reported here is expected to frame a gateway in future for NIR-induced photo-theranostics targeting skin cancer. In this work, a traceable dual-porous mesoporous silica-coated mesoporous carbon nanocomposite (MCN@Si) with high drug loading capacity and high photothermal conversion efficiency (30.5 %) was successfully prepared. Based on the nanocomposite, a pH/redox/near infrared (NIR) multi-stimuli responsive drug delivery system was constructed to realize the accurate drug delivery, drug controlled release and chemo-photothermal synergistic antitumor therapy. MCN@Si was used as a vehicle to load doxorubicin (DOX) with a high drug loading efficacy of 48.2 % and a NIR absorbance agent for photothermal therapy and NIR thermal imaging. Carbon dots (CDs) with proper size were covalently attached to the surface of MCN@Si via disulfide bonds to block the mesopores, preventing DOX premature release from DOX/MCN@Si-CDs. Besides, CDs were served as fluorescent probe to prove the visualization potential of the drug delivery system. DOX was rapidly released at the condition of low pH and high GSH concentration due to the breakage of disulfide bonds and protonation of DOX. Moreover, the local hyperthermia generated by MCN@Si-CDs under NIR irradiation could not only directly kill cells, but also accelerate DOX release and enhance cells sensitivity and permeability. Two-dimensional cells and three-dimensional tumor spheroids assays illustrated that DOX/MCN@Si-CDs + NIR group exhibited a superior thermochemotherapy synergistic treatment effect and the combination index (CI) was 0.378. Biodistribution study showed the biosecurity of preparations and its prolonged detention time in tumor sites. Besides, antitumor experiment in vivo also performed the excellent synergistic inhibition effect. All the results demonstrated that DOX/MCN@Si-CDs is a traceable multi-stimuli responsive nanodelivery system and can achieve efficient chemo-photothermal synergistic antitumor therapy. Lipid Nanocapsules (LNCs) have been used for drug delivery in cells and animal models for several years. LNCs with unique physicochemical properties for favorable biorecognition, biocompatibility and stimuli responsive (pH/temperature etc.) properties i.e., smart-LNCs, are most promising for future nanomedicine applications. However, conventional phase inversion temperature (PIT) method of LNCs preparation may not be suitable for the fabrication of thermally labile drug loaded LNCs and smart-LNCs. Herein, we report for the first time, a novel low temperature (LT) method for the preparation of LNCs (including smart-LNCs of size 25-150 nm), hereafter, named as nanostructure hybrid lipid capsules (nHLCs), comprising safe excipients such as oil (Labrafac™ PG), surfactant (Kolliphor® HS 15, Brij® S100), and lipid (Lipoid S-75, Lipoid S PC-3, Lipoid PE 181/181, Lipoid PC 160/160 etc.). Effects of process parameters on the physicochemical properties of nHLCs were probed to optimize the process. Ternary phase diagram shows that our method allows for great flexibility in the formation of nHLCs with tailored size and composition. This method resulted in drug loaded (regorafenib used as model drug) nHLCs with 95 % encapsulation efficiency and sustained release profile at 37 °C. The drug loaded nHLCs (as prepared or in lyophilized form) has excellent storage stability at 4 °C (for more than one month) as well as biocompatibility similar to that of LNCs prepared by PIT method. Our novel LT method of LNCs (i.e. nHLCs) preparation is a generic method for the development of drug loaded (including thermally labile) and smart-LNCs for future nanomedicine applications. BACKGROUND AND OBJECTIVE Flow generated via peristaltic waves in naturally occurring physical phenomenon inside human body. Its combination with electric and magnetic forces makes it even more versatile in biomedical engineering applications. The results presented in this article are useful in designing artificial tubes, lab-on-a-chip devices for cell manipulation, drug design, flow amalgamation, micro-scale pumps and micro-bots which can be externally controlled by electric and magnetic sensors. Motivated by the aforesaid facts the current investigation is based on the transportation of a couple stress bio-fluid by peristalsis through a convergent channel under the postulates of creeping phenomena and long wavelength, respectively METHODS A closed form solution is acquired for the axial velocity profile, volumetric flow rate and streamlines, respectively. The physical influence of involved parameters on the rheological characteristics are argued analytically with the help of Mathematica software 12.0.1 in dec pump at the micro-scale level, we have used complex peristaltic wave scenario in the boundary walls of the convergent micro-channel. V.BACKGROUND Otitis Media (OM) is one of the most common infections among children in developed countries and may result in temporary conductive hearing loss (HL) if accompanied by middle ear effusion (MEE). Ventilation tube insertion (VTI) is recommended as treatment for recurrent acute OM or chronic MEE with HL. HL may lead to impaired development of psychosocial skills. However, evidence for the developmental consequences of OM and the effect of VTI is inconsistent. The objectives of this study were to investigate 1) whether OM in early childhood is associated with long-term consequences of psychosocial development and 2) if VTI prevents the possible negative consequences of OM. METHODS This study examined prospectively collected data from 52.877 children registered in the Danish National Birth Cohort (DNBC). Information about previous OM-episodes and VTI was obtained through systematic follow-up interviews at seven years, and The Strength and Difficulties Questionnaire (SDQ) containing questions about psychological wellbeing was completed.
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