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The safety, tolerance, and selected renal and non-renal outcome measures were evaluated in 73 SLE patients who received sirolimus therapy for more than 3 months in our institution over the past 21 years. In 12 patients who had lupus nephritis, proteinuria (p = 0.0287), hematuria (p = 0.0232), anti-DNA antibody levels (p = 0.0028) and steroid use were reduced (p = 0.0200). In the non-renal cohort of 61 patients, anti-DNA antibody levels (p = 0.0332) and steroid use were reduced (p = 0.0163). Both in the renal and non-renal cohorts, C3 (renal p = 0.0070; non-renal p = 0.0021) and C4 complement levels were increased (renal p = 0.0063; non-renal p = 0.0042) Adverse effects of mouth sores (2/73), headaches (1/73), and gastrointestinal discomfort were noted in a minority of patients (6/73). Sirolimus was only discontinued in two of 73 patients due to headache and recurrent infections, respectively. This study suggests that sirolimus is well tolerated and exerts long-term therapeutic efficacy in controlling renal and non-renal manifestations of SLE.
Current antiepileptic drugs fail to control approximately 30% of epilepsies. Therefore, there is a need to develop more effective antiepileptic drugs, and medicinal plants provide an attractive source for new compounds. Pergularia daemia (Asclepiadaceae) is used in Cameroon traditional medicine to treat stroke, anemia, inflammation, and epilepsy. Recently, traditional healers claim that an hydro-ethanolic extract of the roots of P. daemia is more effective than an aqueous extract on refractory seizures.
The antiepileptic effect of P. daemia hydro-ethanolic extract was investigated on the pentylenetetrazole kindling model of temporal lobe epilepsy in mice and possible mechanisms of action.
Mice were divided into 8 groups treated as follows normal group received distilled water (10ml/kg, p.o.), control group received distilled water (10ml/kg, p.o.), ethanol group received ethanol (5%, p.o.), positive control received sodium valproate (300mg/kg, p.o.), and test groups received P. daemia hydro-ethanolic (HEective effect. These findings help to explain the beneficial use of these HE extracts of P.daemia in traditional medicine to treat epilepsy in Cameroon.
The HE extract of P. daemia protected mice against kindled seizures and cognitive impairments, and these effects were greater than those of sodium valproate, a widely used antiepileptic drug. These effects may be mediated by neuromodulatory, anti-oxidant, and anti-inflammatory activities, thus suggesting a neuroprotective effect. These findings help to explain the beneficial use of these HE extracts of P.daemia in traditional medicine to treat epilepsy in Cameroon.
Malaria remains a dire health challenge, particularly in sub-Saharan Africa. buy Navitoclax In Uganda, it is the most ordinary condition in hospital admission and outpatient care. The country's meager health services compel malaria patients to use herbal remedies such as Schkuhria pinnata (Lam.) Kuntze ex Thell (Asteraceae). Although in vivo studies tested the antimalarial activity of S. pinnata extracts, plant developmental stages and their effect at different doses remain unknown.
This study aims to determine the effect of the plant developmental stage on the antimalarial activity of S. pinnata in mice and to document the acute oral toxicity profile.
Seeds of S. pinnata were grown, and aerial parts of each developmental stage were harvested. Extraction was done by maceration in 70% methanol. The antimalarial activity was evaluated using chloroquine-sensitive Plasmodium berghei on swiss albino mice, in a chemosuppressive test, at 150, 350, and 700mg/kg, p.o. Standard drugs used were artemether-lumefantrine (0.57+3.43sites and increased survival time with an LD
of 2157mg/kg. Thus, for better antimalarial activity, local communities could consider harvesting S. pinnata at the flowering stage. Further studies are needed to isolate pure compounds from S. pinnata and determine their antimalarial activity.
Together, our findings revealed that the S. pinnata extracts at the flowering stage had superior antimalarial activity compared to other plant developmental stages. Extracts from all developmental stages have demonstrated a dose-dependent suppression of malarial parasites and increased survival time with an LD50 of 2157 mg/kg. Thus, for better antimalarial activity, local communities could consider harvesting S. pinnata at the flowering stage. Further studies are needed to isolate pure compounds from S. pinnata and determine their antimalarial activity.
Different orchids are important in traditional medicine, and species belonging to the genus Bletilla are important. Bletilla species have been used for thousands of years in Traditional Chinese Medicine (TCM) for the treatment of several health disorders, such as gastrointestinal disorders, peptic ulcer, lung disorders, and traumatic bleeding etc. AIM OF THIS REVIEW This review aims to provide a systematic overview and objective analysis of Bletilla species and to find the probable relationship between their traditional use, chemical constituents, and pharmacological activities, while assessing their therapeutic potential in treatment of different human diseases.
Relevant literatures on Bletilla species have been collected using the keywords "Bletilla", "phytochemistry", and "pharmacology" in scientific databases, such as "PubMed", "Scifinder", "The Plant List", "Elsevier", "China Knowledge Resource Integrated databases (CNKI)", "Google Scholar", "Baidu Scholar", and other literature sources, etc. RESULTSdes and stilbenes are the major bioactive chemical constituents of Bletilla genus according to the literatures. However, the mechanism of action of these molecules is yet to be studied. In addition, a detailed comparative analysis of the phytochemistry and biological activities of the three Bletilla species (BS, BO and BF) is highly recommended for understanding their ethnopharmacological uses and applications in clinics. Clinical toxicity tests on BS have been found to be negative, but it can't be used with Aconitum carmichaeli in traditional uses. Furthermore, not many reports are present in the literature regarding the conservation of Bletilla species.
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic recurrent and incurable gastrointestinal diseases with an unknown etiology that leads to a high risk of developing colitis-associated colorectal cancer (CRC).
In this study, we measured the expression characteristics of MELK in IBD and CRC tissues and explored the regulatory effect of OTSSP167 (a MELK-selective inhibitor) on the mice models of colitis and colitis-associated carcinogenesis and analyzed the specific molecular mechanisms.
DSS-induced colitis and colitis-associated carcinogenesis (CAC) model were treated with MELK inhibitor OTSSP167 then the fight against effect of OTSSP167 in the clinical symptoms of colitis and CAC was measured. In addition, underlying mechanism of OTSSP167 treatment in vitro and vivo including anti-ferroptosis and anti-inflammatory response effect was further explored.
We found that pharmacological inhibition of MELK was indicated to significantly alleviaus providing more options for clinical treatment.
Our findings lay a theoretical foundation for the use of OTSSP167 as a treatment for IBD and its inhibition of the occurrence of colitis-associated carcinogenesis; additionally, MELK may be a potentially effective target molecule, thus providing more options for clinical treatment.Stabilization and activation of the p53 tumor suppressor are triggered in response to various cellular stresses, including DNA damaging agents and elevated Reactive Oxygen Species (ROS) like H2O2. When cells are exposed to exogenously added H2O2, ATR/CHK1 and ATM/CHK2 dependent DNA damage signaling is switched on, suggesting that H2O2 induces both single and double strand breaks. These collective observations have resulted in the widely accepted model that oxidizing conditions lead to DNA damage that subsequently mediates a p53-dependent response like cell cycle arrest and apoptosis. However, H2O2 also induces signaling through stress-activated kinases (SAPK, e.g., JNK and p38 MAPK) that can activate p53. Here we dissect to what extent these pathways contribute to functional activation of p53 in response to oxidizing conditions. Collectively, our data suggest that p53 can be activated both by SAPK signaling and the DDR independently of each other, and which of these pathways is activated depends on the type of oxidant used. This implies that it could in principle be possible to modulate oxidative signaling to stimulate p53 without inducing collateral DNA damage, thereby limiting mutation accumulation in both healthy and tumor tissues.
Acute myocardial infarction (AMI) is a cardiovascular disease with high morbidity and mortality, and microRNA-139-5p (miR-139-5p) has been reported to be closely related with myocardial viability. This study aimed to investigate the effects of miR-139-5p on vascular endothelial cells, detect miR-139-5p expression in AMI patients and evaluate its diagnostic value.
A dual-luciferase reporter assay was utilized to confirm the interaction of miR-139-5p with vascular endothelial growth factor receptor-1 (VEGFR-1). Quantitative real-time PCR was used to detect the levels of miR-139-5p and VEGFR-1 in serum and cells. The viability of human umbilical vein endothelial cells (HUVECs) was measured using a cell counting kit-8 assay. The correlation between miR-139-5p and VEGFR-1 was analyzed by Pearson correlation analysis. The diagnostic value of miR-139-5p, cardiac troponin I (cTnI) and creatine kinase isoenzymes (CK-MB) was identified by receiver operating characteristic analysis.
miR-139-5p suppressed cell viability by directly targeting VEGFR-1 in HUVECs. Increased miR-139-5p and decreased VEGFR-1 levels were found in AMI patients and hypoxia-treated HUVECs, and miR-139-5p and VEGFR-1 were shown to be negatively correlated. The diagnostic value of miR-139-5p for AMI screening was high, and the combination of cTnI, CK-MB and miR-139-5p had the highest diagnostic accuracy. miR-139-5p inhibited cell viability by inhibiting VEGFR-1 in hypoxia-treated HUVECs.
miR-139-5p inhibits endothelial cell viability of AMI by inhibiting VEGFR-1, and increased miR-139-5p expression in AMI patients has high diagnostic value for AMI screening, indicating that miR-139-5p may serve as a diagnostic biomarker and molecular therapeutic target for AMI.
miR-139-5p inhibits endothelial cell viability of AMI by inhibiting VEGFR-1, and increased miR-139-5p expression in AMI patients has high diagnostic value for AMI screening, indicating that miR-139-5p may serve as a diagnostic biomarker and molecular therapeutic target for AMI.Kleptoparasitism is assumed to be the main foraging strategy in some animal groups, such as the spiders of the subfamily Argyrodinae (Theridiidae). However, some species may also feed on silk threads, egg sacs, or even their hosts. The conditions determining these alternative foraging tactics remain unknown for most species. We performed field observations, stable isotope analysis and laboratory experiments to investigate kleptoparasitism and araneophagy of Argyrodes elevatus and Faiditus caudatus in webs of Manogea porracea (Araneidae). We evaluated the following hypotheses (1) both species exhibit higher trophic positions than their hosts and closest to an araneophagic sympatric species; (2) host web selection is influenced by the presence of alternative resources (adult male and female, and egg sacs); and (3) they preferentially consume egg sacs instead of stored prey items. Both argyrodines showed higher trophic positions than their female hosts and closest to an araneophagic spider species. The invaders were found mainly on host webs with one adult and egg sacs and with egg sacs only.
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