Mollerupshah1786

GO and KEGG enrichment analyses showed that multiple targets in the antifibrotic pathway were enriched and could be experimentally validated in CD patients and in a mouse model of CD fibrosis. Assays of colon tissues from CD patients showed that intestinal fibrosis was greater in stenoses than in nonstenoses, with upregulation of p-AKT, AKT, p-mTOR, mTOR, p-ERK1/2, ERK1/2, p-PKC, and PKC targets. Treatment of CD fibrosis mice with PD reduced the degree of fibrosis, with downregulation of the p-AKT, AKT, p-mTOR, mTOR, p-ERK1/2, ERK1/2, and PKC targets. Conclusion Network pharmacology analysis was able to predict bioactive compounds in PD and their potential targets in CD. Several of these targets were validated experimentally, providing insight into the pharmacological mechanisms underlying the biological activities of PD in patients with CD.Background In this study, an investigation was conducted on clinical drug trials comprising pregnant women in China that provided data on the quantity, properties, source of funding, and geographical distribution regarding registration and post-marketing studies. Methods We conducted a cross-sectional descriptive study of clinical trials of pregnant women in China on 30 December 2021, and it was registered on the official Drug Clinical Trial Information Management Platform (ChiCTR) (http//www.chinadrugtrials.org.cn) established by the State Food and Drug Administration of China (Chinese FDA). Results This study encompassed 72 registered trials (0.46%, 72/15,539) for data analysis. Of these trials, 43.1% of trials were started between 2013 and 2016, and nearly half of the trials (48.6%) were completed. Industries were listed as the primary sponsor for 95.8% trials. Economically developed eastern China and northern China, accounting for 69.5% of the 72 registered trials, were the most frequently identified study locations. Regarding study designs of these trials, more than half of the trials (70.8%) were randomized, 61.1% were a parallel assignment, 33.3% were phase 3, and half of the trials (54.2%) were open label. In total, 23 trials met the requirements after excluding trials of cancer and/or of postmenopausal women, accounting for 0.15% of the 15,539 registered trials in the ChiCTR websites. Of the 72 clinical trials, 54 drugs for 18 indications were included. Of these indications, the highest proportion of the trials is osteoporosis (27.8%), followed by cancer (22.2%), assisted reproduction (13.9%), and other indications (13.9%). Conclusion This survey revealed a significant shortage of the development, evaluation, and safety trials of pregnancy-related drugs in China. Modifying or adding legislation and providing financial incentives may therefore encourage pharmaceutical companies to conduct additional clinical trials on pregnant women.Background Damp-heat jaundice syndrome (DHJS) is a diagnostic model of traditional Chinese medicine (TCM) that refers to jaundice caused by damp-heat pathogen invasion. DHJS is the most common clinical manifestation of TCM, with yellow skin, yellow eyes and anorexia. ZhiziBaipi Decoction (ZBD) is a classic TCM formula that is effective at treating DHJS and various liver diseases. However, the effective components of ZBD in the context of DHJS and the underlying mechanism are unclear. Purpose This study of ZBD using the DHJS rat model aimed to elucidate the pathobiology of DHJS and the metabolic targets of therapeutic ZBD, construct the network relationship between the components of ZBD and endogenous biomarkers, and clarify the underlying mechanism of ZBD in preventing and treating DHJS. Methods Using chinmedomics as the core strategy, an animal model was generated, and the therapeutic effect of ZBD was evaluated based on behavioral, histopathological and biochemical indicators. Metabonomics tools were used to identify biomarkers of DHJS, TCM-based serum pharmacochemistry was used to analyze the effective constituents of ZBD, and chinmedomics technology was used to identify ZBD components highly related to DHJS biomarkers. Results A total of 42 biomarkers were preliminarily identified, and ZBD significantly affected the levels of 29 of these biomarkers. A total of 59 compounds in ZBD were characterized in vivo. According to chinmedomics analysis, the highly correlated components found in blood were isoformononetin, 3-O-feruloylquinic acid, glycyrrhizic acid, oxyberberine, obaculactone and five metabolites. Conclusions Chinmedomics combined with UPLC-MS/MS was used to study the targets and effective constituents of ZBD for the treatment of DHJS.Primary melanoma aggressiveness is determined by rapid selection and growth of cellular clones resistant to conventional treatments, resulting in metastasis and recurrence. In addition, a reprogrammed tumor-immune microenvironment supports melanoma progression and response to therapy. There is an urgent need to develop selective and specific drug delivery strategies for modulating the interaction between cancer cells and immune cells within the tumor microenvironment. This study proposes a novel combination therapy consisting of sequential administration of simvastatin incorporated in IL-13-functionalized long-circulating liposomes (IL-13-LCL-SIM) and doxorubicin encapsulated into PEG-coated extracellular vesicles (PEG-EV-DOX) to selectively target both tumor-associated macrophages and melanoma cells. To this end, IL-13 was conjugated to LCL-SIM which was obtained via the lipid film hydration method. EVs enriched from melanoma cells were passively loaded with doxorubicin. The cellular uptake of rhodamine-taggcordingly, strong inhibition of tumor growth in the group treated with the sequential combination therapy was reported in vivo. Our data suggested that the antitumor action of the combined treatment was exerted through strong inhibition of several pro-angiogenic factors (VEGF, bFGF, and CD31) and oxidative stress-induced upregulation of pro-apoptotic protein Bax. This novel drug delivery strategy based on combined active targeting of both cancer cells and immune cells was able to induce a potent antitumor effect by disruption of the reciprocal interactions between TAMs and melanoma cells.Despite the growing number of new drugs approved for the treatment of inflammatory bowel disease (IBD), the long-term clinical use of thiopurine therapy and the well-known properties of conventional drugs including azathioprine have made their place in IBD therapy extremely valuable. Despite the fact that thiopurine S-methyltransferase (TPMT) polymorphism has been recognized as a major cause of the interindividual variability in the azathioprine response, recent evidence suggests that there might be some yet unknown causes which complicate dosing strategies causing either failure of therapy or toxicity. Increasing evidence suggests that gut microbiota, with its ability to release microbial enzymes, affects the pharmacokinetics of numerous drugs and subsequently drastically alters clinical effectiveness. Azathioprine, as an orally administered drug which has a complex metabolic pathway, is the prime illustrative candidate for such microbial metabolism of drugs. Comprehensive databases on microbial drug-metabolizing enzymes have not yet been generated. This study provides insights into the current evidence on microbiota-mediated metabolism of azathioprine and systematically accumulates findings of bacteria that possess enzymes required for the azathioprine biotransformation. Additionally, it proposes concepts for the identification of gut bacteria species responsible for the metabolism of azathioprine that could aid in the prediction of dose-response effects, complementing pharmacogenetic approaches already applied in the optimization of thiopurine therapy of IBD. 1-Naphthyl PP1 clinical trial It would be of great importance to elucidate to what extent microbiota-mediated metabolism of azathioprine contributes to the drug outcomes in IBD patients which could facilitate the clinical implementation of novel tools for personalized thiopurine treatment of IBD.Background Polysaccharide peptide (PSP) extract of Coriolus versicolor (L.) Quél. (1886) (Trametes; Polyporaceae) is increasingly used in cancer to support the immune system. However, its interaction with tamoxifen is unknown. Aim of the study To investigate the effect of a PSP extract on the pharmacokinetics, biochemical parameters, and depletion of tamoxifen. Methods The pharmacokinetic and biochemical parameters of tamoxifen (20 mg/mL oral single dose and repeated dosing for 12 days) was investigated in female Sprague Dawley rats with or without PSP (340 mg/kg orally for 7 days) (n = 5 per group). Tamoxifen (5 µM) depletion rate with PSP (10-100 μg/mL) was measured in female rat hepatic microsomes in vitro. Results Compared to tamoxifen alone, the time to reach maximum concentration (Tmax) significantly increased by 228% (4.15 ± 1.15 versus 13.6 ± 2.71 h) in the single tamoxifen dose with PSP and 93% (6 ± 2.17 versus 11.6 ± 0.4 h) in the repeated tamoxifen dosing with PSP (p 0.05). PSP extract did not significantly alter in vitro intrinsic clearance of tamoxifen compared to tamoxifen control. Conclusion With the increased use of PSP as an adjunct therapy, this study highlights the importance of clinician's knowledge of its interaction with tamoxifen to avoid compromising clinical actions and enhancing clinical therapy.Despite the recent advances in HIV treatment, HIV-associated neurocognitive disorder (HAND) prevalence remains high, especially in the mild forms. Current recommendations endorse routine screening for HAND and early identification, but there are several obstacles in diagnosing and managing cognitive impairment in people living with HIV. The purpose of this review is to provide an overview of the concepts and diagnostic tools in the field of HAND and report on the strengths and limitations of currently available approaches.

Sickle cell disease (SCD) and thalassemia are common inherited blood disorders in Saudi Arabia, especially in Jazan Province. Patients with these disorders require multiple blood transfusions, which may lead to alloimmunization because of mismatched blood group antigens. In this study, we examined the alloimmunization and autoimmunization rates in patients with SCD and thalassemia together with the involved antibodies.

A cross-sectional study was conducted to review the transfusion history records of patients with SCD and thalassemia at Prince Mohammed bin Nasser Hospital, Jazan Province, Saudi Arabia.

Four-hundred thirty-eight patients (385 with SCD, 52 with β-thalassemia, and 1 with α-thalassemia) were received leukoreduced red cell transfusions. The alloimmunization and autoimmunization rates in patients with SCD were 12.98% and 0.52%, respectively. In patients with thalassemia, the alloimmunization and autoimmunization rates were 13.21% and 3.77%, respectively. The most prevalent antibodies in the study population were anti-E (17.19%) and anti-K (14.06%).

The alloimmunization and autoimmunization rates were determined in patients with SCD and thalassemia in Jazan Province, Saudi Arabia. The results highlight the need for extended phenotyping to include ABO, RH (D, C, c, E, e), K, Fy

, Fy

, Jk

and Jk

antigens in the screening panel. This will benefit patients to ensure better transfusion practices.

The alloimmunization and autoimmunization rates were determined in patients with SCD and thalassemia in Jazan Province, Saudi Arabia. The results highlight the need for extended phenotyping to include ABO, RH (D, C, c, E, e), K, Fya, Fyb, Jka and Jkb antigens in the screening panel. This will benefit patients to ensure better transfusion practices.