Effects Of Drugs Research Articles

Study of the Effect of Fresh Green Asparagus officinalis L. Stems Extract and Metformin Drug on Induced Polycystic Ovary Syndrome (PCOS) in Female Albino Rats

During this research, Polycystic Ovary Syndrome (PCOS) was studied and the effect of Metformin Drug and an extract of fresh Asparagus officinalis L. stems on it was studied. The study involved 20 adult female albino rats divided into four groups, each containing five female rats. The first group received a physiological saline solution, while the second group was induced with Polycystic Ovary Syndrome (PCOS) by being dosed with Letrozole. The third group, after the induction of PCOS, was treated with Metformin, and the fourth group was dosed with Fresh Asparagus officinalis L. stems extract. The study focused on hormonal and Histological changes. The results showed that the group of rats with PCOS induced by Letrozole had a significant decrease in the levels of Progesterone (Prog.) and Oestradiol (E2) hormones, and a significant increase in Testosterone (Testo.) compared to the control group. Dosing rats with Fresh Asparagus officinalis L. stems extract led to a significant decrease in (E2) hormone level and a significant increase in Progesterone (Prog.) hormone level compared with the control group. Dosing rats with Metformin led to a significant decrease in (E2) hormone level and a significant increase in Progesterone (Prog.) and Testosterone (Testo.) hormone levels compared to the control group. The results also indicated significant changes in hormone levels between Treatment groups and PCOS induction group. The histological study revealed changes in the shape of the ovary, the appearance of cystic structures, congestion of blood vessels, and increased ovarian cellularity. Metformin showed fewer Histological changes, while Asparagus officinalis L. stems extract had a therapeutic effect with moderate severity, leading to the disappearance of cystic vesicles and the appearance of corpus luteum and primary vesicles. In conclusion, we conclude that both the therapeutic agents Metformin and the extract of Fresh Asparagus officinalis L. stems showed a therapeutic effect on Polycystic Ovary Syndrome, as Metformin drug showed a treatment for this Syndrome, but it requires a long period to show this result, meaning we need more than 28 days, which is the duration of the study, but Asparagus officinalis L. stems extract had Faster healing effect within just 28 days. Fresh Green, tender Asparagus officinalis L. stems is one of the significant medicinal plants that is used to treat or prevent polycystic ovarian syndrome. Research has shown that it is an effective treatment for the condition. Future researchers studying polycystic ovarian syndrome will find this article useful.

The Impact Of Clients' Knowledge On Compliance With Anti-Tuberculosis Medication At Home

Pulmonary tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, namely acid-fast bacteria. Successful treatment of patients with tuberculosis (TB) is a problem in today's society. One of the reasons for the increase in pulmonary TB cases is the low level of education of sufferers. One of the causes of failure of tuberculosis treatment therapy is the side effects of anti-tuberculosis drugs (OAT) which can affect the adherence to medication in tuberculosis patients. The success of TB treatment is compliance in taking anti-tuberculosis medication at the prescribed dose. The aim of this research was to determine the relationship between clients' knowledge of pulmonary tuberculosis and compliance with taking anti-pulmonary tuberculosis medication at Harapan Pematang Siantar Hospital. This research was conducted at Harapan Pematangsiantar Hospital in May 2023. This type of research is descriptive quantitative correlational with a cross-sectional approach. Data collection was carried out using a questionnaire with the Gutman scale. The population of this study was all outpatient clinic patients at Harapan Pematang Siantar Hospital in October-December 2022. The sampling technique was accidental sampling, namely 58 respondents who came in May 2023. Statistical test results used the chi square test with a confidence level of 95% (α = 0.05) shows the p value = 0.001, meaning that there is a relationship between the level of knowledge of tuberculosis clients and compliance with taking anti-tuberculosis medication at Harapan Pematang Siantar Hospital in 2023

Experimental and computational insights of Albizia amara phytoconstituents targeting anthranilate phosphoribosyltransferase from Malassezia globosa

The fungus Malassezia globosa is often responsible for superficial mycoses posing significant treatment challenges because of the unfavourable side effects of available antifungal drugs. To reduce potential hazards to the host and overcome these hurdles, new therapeutic medicines must be developed that selectively target enzymes unique to the pathogen. This study focuses on the enzyme anthranilate phosphoribosyltransferase (AnPRT), which is vital to M. globosa's tryptophan production pathway. To learn more about the function of the AnPRT enzyme, we modeled, validated, and simulated its structure. Moreover, many bioactive components were found in different extracts from the plant Albizia amara after phytochemical screening. Interestingly, at doses ranging from 500 to 2000 µg/ml, the chloroform extract showed significant antifungal activity, with inhibition zones measured between 11.0 ± 0.0 and 25.6 ± 0.6 mm. According to molecular docking analyses, the compounds from the active extract, particularly 2-tert-Butyl-4-isopropyl-5-methylphenol, interacted with the AnPRT enzyme's critical residues, ARG 205 and PHE 214, with an effective binding energy of -4.9 kcal/mol. The extract's revealed component satisfies the requirements for drug-likeness and shows promise as a strong antifungal agent against infections caused by M. globosa. These findings imply that using plant-derived chemicals to target the AnPRT enzyme is a viable path for the creation of innovative antifungal treatments.

TnP and AHR-CYP1A1 Signaling Crosstalk in an Injury-Induced Zebrafish Inflammation Model

Aryl Hydrocarbon Receptor (AHR) signaling is crucial for regulating the biotransformation of xenobiotics and physiological processes like inflammation and immunity. Meanwhile, Thalassophryne nattereri Peptide (TnP), a promising anti-inflammatory candidate from toadfish venom, demonstrates therapeutic effects through immunomodulation. However, its influence on AHR signaling remains unexplored. This study aimed to elucidate TnP’s molecular mechanisms on the AHR–cytochrome P450, family 1 (CYP1) pathway upon injury-induced inflammation in wild-type (WT) and Ahr2-knockdown (KD) zebrafish larvae through transcriptomic analysis and Cyp1a reporters. TnP, while unable to directly activate AHR, potentiated AHR activation by the high-affinity ligand 6-Formylindolo [3,2-b]carbazole (FICZ), implying a role as a CYP1A inhibitor, confirmed by in vitro studies. This interplay suggests TnP’s ability to modulate the AHR-CYP1 complex, prompting investigations into its influence on biotransformation pathways and injury-induced inflammation. Here, the inflammation model alone resulted in a significant response on the transcriptome, with most differentially expressed genes (DEGs) being upregulated across the groups. Ahr2-KD resulted in an overall greater number of DEGs, as did treatment with the higher dose of TnP in both WT and KD embryos. Genes related to oxidative stress and inflammatory response were the most apparent under inflamed conditions for both WT and KD groups, e.g., Tnfrsf1a, Irf1b, and Mmp9. TnP, specifically, induces the expression of Hspa5, Hsp90aa1.2, Cxcr3.3, and Mpeg1.2. Overall, this study suggests an interplay between TnP and the AHR-CYP1 pathway, stressing the inflammatory modulation through AHR-dependent mechanisms. Altogether, these results may offer new avenues in novel therapeutic strategies, such as based on natural bioactive molecules, harnessing AHR modulation for targeted and sustained drug effects in inflammatory conditions.

EFFICIENCY OF TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION AND PIROXICAM TO ALLEVIATE PAIN DURING ORTHODONTIC TOOTH SEPARATION - A PROSPECTIVE STUDY

Objective: This study was conducted to assess the effectiveness of TENS in comparison with TENS-Placebo and prophylactic Piroxicam (20 mg) for pain control before orthodontic tooth separation by Elastomeric separators, Brasswire and Kesling separators. Study design: 108 patients seeking orthodontic treatment were categorically administered extraoral TENS, TENS-Placebo and Piroxicam (20 mg) using Elastomeric, Kesling and Brasswire separators prior to their orthodontic treatment. The subjects were instructed to rate their pain 2, 6, 12, 24 and 48 hours after the procedure on a Visual Analog Scale. Results: No statistically significant difference was found in the mean VAS scores when TENS group was compared with Piroxicam. However, significant differences were found between the mean VAS scores when placebo TENS group was compared to the aforementioned groups. Maximum pain was perceived at 24 hours with elastomeric and Kesling springs, but brasswire separators were most painful 6 hours after placement altogether. At all time stamps, pain felt was significantly less with brasswire separators than elastomeric separators and Kesling springs. Conclusion: TENS was found to be equally effective in reducing pain as Piroxicam. TENS could be thus stated as an effective pain management modality which is safe, comfortable and easy to use and also eliminates adverse drug effects of NSAIDs like GI irritation and reduced orthodontic tooth movement.

Synthesis and in vitro study of biodegradable and thermoresponsive polymer based on polysuccinimide for drug delivery

Hydrogels, defined as polymer networks with a high water content and insoluble in water, have emerged as pivotal materials in biomedical research due to their resemblance to the natural extracellular matrix. The aim of this study is to develop an injectable, thermoresponsive, and biodegradable hydrogel. The hydrogel (PSI-t) was derived from poly (aspartic acid) (PSI) by grafting hydrophobic dodecylamine (DA) and hydrophilic ethanolamine (EA) groups onto its backbone. PSI-t was found to exhibit a unique sol state at room temperature, which facilitates facile injection, and undergoes rapid gelation at physiological temperatures, highlighting its potential as an injectable thermosensitive hydrogel for targeted drug delivery. In vitro tests confirmed the biocompatibility of the thermosensitive hydrogel, and sustained drug release studies using the model drug, acetaminophen (AP), underscored the efficacy of the hydrogel as a controlled release vehicle. Furthermore, the hydrogel was found to be easily eliminated through bio-hydrolysis, thus enabling prolonged drug effects while mitigating any potential toxicity. These findings suggest that PSI-t is a promising candidate for an innovative and injectable drug delivery system in biomedical applications.

Neurocognitive function and medical care utilization in Veterans treated for substance use disorder

BackgroundVeterans with substance use disorder (SUD) are at high risk for cognitive problems due to neurotoxic effects of chronic drug and alcohol use coupled in many cases with histories of traumatic brain injury (TBI). These problems may in turn result in proneness to SUD relapse and reduced adherence to medical self-care regimens and therefore reliance on health care systems. However, the direct relationship between cognitive function and utilization of Veterans Health Administration (VHA) SUD and other VHA health care services has not been evaluated. We sought initial evidence as to whether neurocognitive performance relates to repeated health care engagement in Veterans as indexed by estimated VHA care costs.MethodsNeurocognitive performance in 76 Veterans being treated for SUD was assessed using CNS-Vital Signs, a commercial computerized cognitive testing battery, and related to histories of outpatient and inpatient/residential care costs as estimated by the VHA Health Economics Resource Center.ResultsAfter controlling for age, an aggregate metric of overall neurocognitive performance (Neurocognition Index) correlated negatively with total VHA health care costs, particularly with SUD-related outpatient care costs but also with non-mental health-related care costs. Barratt Impulsiveness Scale scores also correlated positively with total VHA care costs.ConclusionsIn Veterans receiving SUD care, higher impulsivity and lower cognitive performance were associated with greater health care utilization within the VHA system. This suggests that veterans with SUD who show lower neurocognitive performance are at greater risk for continued health problems that require healthcare engagement. Cognitive rehabilitation programs developed for brain injury and other neurological conditions could be tried in Veterans with SUD to improve their health outcomes.

Effect of Alcohol And Narcotic Drug Intake Among Undergraduates Of Kwara State University Malete, Nigeria

Background: Alcohol and narcotic drug use have a long history together. Students in postsecondary institutions frequently use alcohol along with other substances like cannabis, nicotine, tramadol, codeine, and other amphetamines. These substances have detrimental effects on both the user and society at large, so it is absolutely essential to discover what is causing the continued use of these substances. Aim: To determine the effect of alcohol and narcotic intake among undergraduates of Kwara state university, Malete, Nigeria Method: This study is a descriptive cross-sectional study, designed to assess the effect of alcohol and narcotic intake among undergraduates in Kwara State University, malete using a qualitative method of data collection. The questionnaire was administered to determine the sample size using a simple random technique to get the desired sample size from the study population Result: Relationship between the social demographic response of the participants regarding their knowledge, effects of narcotic drugs and alcohol on the body and types of narcotic commonly used by undergraduates and factors motivating the use of narcotic drugs alcohol. Using Chi-Square set with the level of significance p<0.05 alongside with degree of freedom. Considering the relationship between the gender of the respondents towards their knowledge about drugs and narcotics among the undergraduates, 40(20%) were female respondents, while 160(80%) of them were male respondents. P. value = 0.000 < 0.05, which shows that it is significant, thereby rejecting the null hypothesis. Considering the relationship between the age of the respondents and the knowledge, 17-18 years were 40 (20%), 19-20years were 80(40%) while 21 and above were 80(40%) with P-value = 0.00 < 0.05 indicating that it is significant, thereby rejecting the null hypothesis. Also, regarding the relationship between religion and their knowledge about knowledge, 100(50%) of the respondents were Muslims, 60(40%) were Christians, while 20(10%) were traditional. P-value = 0.00 < 0.05 meaning that it is significant, thereby rejecting the null hypothesis. Conclusion: On our campus, there is an urgent need for preventive public health measures. It is recommended to launch more awareness efforts about the harmful effects of alcohol and narcotic medications. The use of alcohol and other drugs presents a serious threat to our future generations. Every single person ought to be discouraged by it.

Harnessing the Biomimetic Effect of Macromolecular Crowding in the Cell-Derived Model of Clubfoot Fibrosis.

Fibrotic changes in pediatric clubfoot provide an opportunity to improve corrective therapy and prevent relapses with targeted drugs. This study defines the parameters of clubfoot fibrosis and presents a unique analysis of a simple pseudo-3D in vitro model for disease-specific high-throughput drug screening experiments. The model combines clubfoot-derived fibroblasts with a biomimetic cultivation environment induced by the water-soluble polymers Ficoll and Polyvinylpyrrolidone, utilizing the principle of macromolecular crowding. We achieved higher conversion of soluble collagen into insoluble collagen, accelerated formation of the extracellular matrix layer and upregulated fibrosis-related genes in the mixed Ficoll environment. To test the model, we evaluated the effect of a potential antifibrotic drug, minoxidil, emphasizing collagen content and cross-linking. While the model amplified overall collagen deposition, minoxidil effectively blocked the expression of lysyl hydroxylases, which are responsible for the increased occurrence of specific collagen cross-linking in various fibrotic tissues. This limited the formation of collagen cross-link in both the model and control environments. Our findings provide a tool for expanding preclinical research for clubfoot and similar fibroproliferative conditions.

The effect of oxidative stress on the kidneys

Free radicals have a strong ability to harm and destroy vital molecules in the body's cells, such as carbohydrates, lipids, proteins, and nucleic acids. The harm resulting from free radicals plays a major role in constantly increasing these radicals and in a series of reactions that lead to the destruction of vital molecules in the cell. Free radicals play a helpful role in destroying malignant tumor tissues by radiation, and they also have a role in demonstrating the action and effect of toxic substances and drugs. They also participate in various vital processes within the body's tissues as intermediate compounds, as biochemical stimulants work to stimulate enzymes through the association of the free radical with the protein part of the enzyme, thus stimulating the working mechanisms of that enzyme, such as the enzymes Catalase, Reductase , Peroxidase, and Oxidase. Therefore, the current review dealt with a study on oxidative stress, including free radicals and antioxidants, and the effects of oxidative stress resulting from the use of drugs and antibiotics on some organs such as the liver, heart, aorta, lung and testicles in general, and the kidneys in detail by studying their effects on blood dynamics within the glomerulus and tubule cell toxicity and inflammation. And crystal nephropathy, rhabdomyolysis, vascular disorders, and nephron toxicity.

Drug evaluation platform based on non-destructive and real-time in situ organoid fate state monitoring by graphene field-effect transistor

3D organoid models have been widely used in drug evaluation because they effectively mimic physiological conditions and cell–cell interactions. However, current organoid-based drug evaluation heavily relies on invasive methods like qRT-PCR and immunofluorescence quantification, which disrupts the organoid’s structure and physiological function during the evaluation process. Therefore, it is urgent to develop a non-destructive drug evaluation platform to continuously monitor organoid fate. Here, a non-destructive and real-time in situ platform based on field effect transistor sensor (NDRS-FET) was developed to monitor organoid fate and obtained accurate drug evaluation by conducting the dynamic models. Using liver organoid as the model, the transition kinetics of liver organoid fate in response to candidate drug compounds were recorded by the NDRS-FET platform. OSM, FH1 and BG45 were successfully identified as effective regulators of liver organoid fate. Compared to traditional methods, the NDRS-FET platform could not only accurately capture the drug effect on organoid in real time, but also reduce the intergroup deviation among samples, providing more accurate and reliable tool for drug development and screening.

Utilizing an acute hyperthermia-induced seizure test and pharmacokinetic studies to establish optimal dosing regimens in a mouse model of Dravet syndrome.

The current standard of care for Dravet syndrome (DS) includes polytherapy after inadequate seizure control with one or more monotherapy approaches. Treatment guidelines are often based on expert opinions, and finding an optimal balance between seizure control and adverse drug effects can be challenging. This study utilizes the efficacy and pharmacokinetic assessment of a second-line treatment regimen that combines clobazam and sodium valproate with an add-on drug as a proof-of-principle approach to establish an effective therapeutic regimen in a DS mouse model. We evaluated the efficacy of add-on therapies stiripentol, cannabidiol, lorcaserin, or fenfluramine added to clobazam and sodium valproate against hyperthermia-induced seizures in Scn1aA1783V/WT mice. Clobazam, N-desmethyl clobazam (an active metabolite of clobazam), sodium valproate, stiripentol, and cannabidiol concentrations were quantified in plasma and brain using liquid chromatography-tandem mass spectrometry for the combinations deemed effective against hyperthermia-induced seizures. The concentration data were used to calculate pharmacokinetic parameters via noncompartmental analysis in Phoenix WinNonLin. Higher doses of stiripentol or cannabidiol, in combination with clobazam and sodium valproate, were effective against hyperthermia-induced seizures in Scn1aA1783V/WT mice. In Scn1aWT/WT mice, brain clobazam and N-desmethyl clobazam concentrations were higher in the triple-drug combinations than in the clobazam monotherapy. Stiripentol and cannabidiol brain concentrations were greater in the triple-drug therapy than when given alone. A polypharmacy strategy may be a practical preclinical approach to identifying efficacious compounds for DS. The drug-drug interactions between compounds used in this study may explain the potentiated efficacy of some polytherapies.

Liver-on-a-Chip Integrated with Label-Free Optical Biosensors for Rapid and Continuous Monitoring of Drug-Induced Toxicity.

Drug toxicity assays using conventional 2D static cultures and animal studies have limitations preventing the translation of potential drugs to the clinic. The recent development of organs-on-a-chip platforms provides promising alternatives for drug toxicity/screening assays. However, most studies conducted with these platforms only utilize single endpoint results, which do not provide real-time/ near real-time information. Here, a versatile technology is presented that integrates a 3Dliver-on-a-chip with a label-free photonic crystal-total internal reflection (PC-TIR) biosensor for rapid and continuous monitoring of the status of cells. This technology can detect drug-induced liver toxicity by continuously monitoring the secretion rates and levels of albumin and glutathione S-transferase α (GST-α) of a 3D liver on-a-chip model treated with Doxorubicin. The PC-TIR biosensor is based on a one-step antibody functionalization with high specificity and a detection range of 21.7ngmL-1 to 7.83 x 103ngmL-1 for albumin and 2.20ngmL-1 to 7.94 x 102ngmL-1 for GST-α. This approach provides critical advantages for the early detection of drug toxicity and improved temporal resolution to capture transient drug effects. The proposed proof-of-concept study introduces a scalable and efficient plug-in solution for organ-on-a-chip technologies, advancing drug development and in vitro testing methods by enabling timely and accurate toxicity assessments.

Examining the effect of prescription drug monitoring program integration and mandatory use policies on the distribution of methadone and buprenorphine for opioid use disorder, United States, 2009–2021

BackgroundPrescription drug monitoring programs (PDMPs) have been shown to reduce opioid prescribing for pain, but it is not well understood whether PDMPs influence utilization of medications for opioid use disorder. PDMP integration and mandatory use policies are two approaches implemented by states to increase use of PDMPs by prescribers. This study examined the effect of these approaches on distribution of methadone and buprenorphine from 2009 to 2021 for 50 states and DC. MethodsThe effect of PDMP integration and mandatory use policies on four outcomes (distribution of buprenorphine to opioid treatment programs, distribution of buprenorphine to pharmacies, distribution of methadone to opioid treatment programs, and the total combined distribution of methadone and buprenorphine) was estimated using a Callaway and Sant’Anna difference-in-differences model, controlling for co-occurring opioid-related state policies. ResultsDistribution of buprenorphine to pharmacies decreased 8 % (95 % CI −14 %, −1 %) following implementation of mandatory use policies. Distribution of methadone to opioid treatment programs increased 17 % (95 % CI 4 %, 34 %) and the total combined distribution of methadone and buprenorphine increased 6 % (95 % CI −0 %, 14 %) following the joint implementation of both approaches. ConclusionDistribution of methadone and buprenorphine has increased since 2009, but less than a quarter of people with opioid use disorder currently receive these medications. We observed a small net benefit of PDMP integration and mandatory use policies on distribution of methadone and buprenorphine. Policymakers should continue to assess the impact of PDMPs on access to medications for opioid use disorder and consider additional approaches to increase access to treatment.

Dispensed prescription medications and short-term risk of pulmonary embolism in Norway and Sweden

Scandinavian electronic health-care registers provide a unique setting to investigate potential unidentified side effects of drugs. We analysed the association between prescription drugs dispensed in Norway and Sweden and the short-term risk of developing pulmonary embolism. A total of 12,104 pulmonary embolism cases were identified from patient- and cause-of-death registries in Norway (2004–2014) and 36,088 in Sweden (2005–2014). A case-crossover design was used to compare individual drugs dispensed 1–30 days before the date of pulmonary embolism diagnosis with dispensation in a 61–90 day time-window, while controlling for the receipt of other drugs. A BOLASSO approach was used to select drugs that were associated with short-term risk of pulmonary embolism. Thirty-eight drugs were associated with pulmonary embolism in the combined analysis of the Norwegian and Swedish data. Drugs associated with increased risk of pulmonary embolism included certain proton-pump inhibitors, antibiotics, antithrombotics, vasodilators, furosemide, anti-varicose medications, corticosteroids, immunostimulants (pegfilgrastim), opioids, analgesics, anxiolytics, antidepressants, antiprotozoals, and drugs for cough and colds. Mineral supplements, hydrochlorothiazide and potassium-sparing agents, beta-blockers, angiotensin 2 receptor blockers, statins, and methotrexate were associated with lower risk. Most associations persisted, and several additional drugs were associated, with pulmonary embolism when using a longer time window of 90 days instead of 30 days. These results provide exploratory, pharmacopeia-wide evidence of medications that may increase or decrease the risk of pulmonary embolism. Some of these findings were expected based on the drugs' indications, while others are novel and require further study as potentially modifiable precipitants of pulmonary embolism.

Cross-lingual Natural Language Processing on Limited Annotated Case/Radiology Reports in English and Japanese: Insights from the Real-MedNLP Workshop.

Textual datasets (corpora) are crucial for the application of natural language processing (NLP) models. However, corpus creation in the medical field is challenging, primarily because of privacy issues with raw clinical data such as health records. Thus, the existing clinical corpora are generally small and scarce. Medical NLP (MedNLP) methodologies perform well with limited data availability. We present the outcomes of the Real-MedNLP workshop, which was conducted using limited and parallel medical corpora. Real-MedNLP exhibits three distinct characteristics: (1) Limited Annotated Documents: The training data comprises only a small set (approximately 100) of case reports (CRs) and radiology reports (RRs) that have been annotated. (2) Bilingually Parallel: The constructed corpora are parallel in Japanese and English. (3) Practical Tasks: The workshop addresses fundamental tasks, such as named entity recognition and applied practical tasks. We propose three tasks: named entity recognition (NER) of approximately 100 available documents (Task 1), NER based only on annotation guidelines for humans (Task 2), and clinical applications (Task 3) consisting of adverse drug effects (ADE) detection for CRs and identical case identification (CI) for RRs. Nine teams participated in this study. The best systems achieved 0.65 and 0.89 F1-scores for CRs and RRs in Task 1, whereas the top scores in Task 2 decreased by 50-70%. In Task 3, ADE reports were detected by up to 0.64 F1-score, and CI scored up to 0.96 binary accuracy. Most systems adopt medical-domain-specific pre-trained language models using data augmentation methods. Despite the challenge of limited corpus size in Tasks 1 and 2, recent approaches are promising because the partial match scores reached approximately 0.8-0.9 F1-scores. Task 3 applications revealed that the different availabilities of external language resources affected the performance per language.

Exploring the Effects and Potential Mechanisms of Hesperidin for the Treatment of CPT-11-Induced Diarrhea: Network Pharmacology, Molecular Docking, and Experimental Validation.

Chemotherapy-induced diarrhea (CID) is a potentially serious side effect that often occurs during anticancer therapy and is caused by the toxic effects of chemotherapeutic drugs on the gastrointestinal tract, resulting in increased frequency of bowel movements and fluid contents. Among these agents, irinotecan (CPT-11) is most commonly associated with CID. Hesperidin (HPD), a flavonoid glycoside found predominantly in citrus fruits, has anti-oxidation properties and anti-inflammation properties that may benefit CID management. Nevertheless, its potential mechanism is still uncertain. In this study, we firstly evaluated the pharmacodynamics of HPD for the treatment of CID in a mouse model, then used network pharmacology and molecular docking methods to excavate the mechanism of HPD in relieving CID, and finally further proved the predicted mechanism through molecular biology experiments. The results demonstrate that HPD significantly alleviated diarrhea, weight loss, colonic pathological damage, oxidative stress, and inflammation in CID mice. In addition, 74 potential targets for HPD intervention in CID were verified by network pharmacology, with the top 10 key targets being AKT1, CASP3, ALB, EGFR, HSP90AA1, MMP9, ESR1, ANXA5, PPARG, and IGF1. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the PI3K-Akt pathway, FoxO pathway, MAPK pathway, TNF pathway, and Ras pathway were most relevant to the HPD potential treatment of CID genes. The molecular docking results showed that HPD had good binding to seven apoptosis-related targets, including AKT1, ANXA5, CASP3, HSP90AA1, IGF1, MMP9, and PPARG. Moreover, we verified apoptosis by TdT-mediated dUTP nick-end labeling (TUNEL) staining and immunohistochemistry, and the hypothesis about the proteins above was further verified by Western blotting in vivo experiments. Overall, this study elucidates the potential and underlying mechanisms of HPD in alleviating CID.

Sexual side effects of antipsychotic drugs in schizophrenia: Protocol for a systematic review with single-arm, pairwise and network meta-analysis of randomized controlled trials and non-randomized studies

Introduction Sexual dysfunctions are common yet underreported side effects of antipsychotics for schizophrenia, affecting 30-80% of treated individuals. These side effects can severely impact social interactions and treatment adherence for individuals with schizophrenia, but comprehensive comparative evidence assessing the risk profiles of different antipsychotics is lacking. This study aims to address this gap using network meta-analysis that integrates data from both randomized-controlled trials (RCTs) and non-randomized studies (NRS). Protocol This systematic review will include both RCTs and NRS focusing on participants with schizophrenia or schizophrenia-like psychoses, without restrictions on symptoms, gender, ethnicity, age, or setting. For interventions, all second-generation antipsychotics will be included. The primary outcome will be the occurrence of at least one sexual adverse event of any kind. Secondary outcomes will be the occurrence of any sexual adverse event evaluated in men and women separately, and any adverse event related to the three phases of sexual response cycle separately: desire (e.g. libido, sexual thoughts), arousal (e.g. erection, lubrication) and orgasm (e.g. ejaculation, anorgasmia), and any adverse effect related to breast dysfunction and menstruation irregularities. Study selection and data extraction will be performed independently by two reviewers. The Cochrane Risk of Bias tool 1 and ROBINS-I will be employed to evaluate the risk of bias for RCTs and NRS, respectively. Single-arm meta-analysis of proportions will synthesize the average frequency of sexual adverse events in treated participants. Pairwise and network meta-analysis of RCTs and NRS will be used to evaluate comparative tolerability. Subgroup and sensitivity analyses will explore possible heterogeneity in results and validate the findings’ robustness. The quality of the evidence will be evaluated using GRADE. Discussion This study will provide vital insights into the sexual side effects of antipsychotics by combining evidence from clinical trials and real-world practice, facilitating better decision-making in choosing the optimal antipsychotic for individuals.

Misprogramming of glucose metabolism impairs recovery of hippocampal slices from neuronal GLT-1 knockout mice and contributes to excitotoxic injury through mitochondrial superoxide production.

We have previously reported a failure of recovery of synaptic function in the CA1 region of acute hippocampal slices from mice with a conditional neuronal knockout (KO) of GLT-1 (EAAT2, Slc1A2) driven by synapsin-Cre (synGLT-1 KO). The failure of recovery of synaptic function is due to excitotoxic injury. We hypothesized that changes in mitochondrial metabolism contribute to the heightened vulnerability to excitotoxicity in the synGLT-1 KO mice. We found impaired flux of carbon from 13C-glucose into the tricarboxylic acid cycle in synGLT-1 KO cortical and hippocampal slices compared with wild-type (WT) slices. In addition, we found downregulation of the neuronal glucose transporter GLUT3 in both genotypes. Flux of carbon from [1,2-13C]acetate, thought to be astrocyte-specific, was increased in the synGLT-KO hippocampal slices but not cortical slices. Glycogen stores, predominantly localized to astrocytes, are rapidly depleted in slices after cutting, and are replenished during exvivo incubation. In the synGLT-1 KO, replenishment of glycogen stores during exvivo incubation was compromised. These results suggest both neuronal and astrocytic metabolic perturbations in the synGLT-1 KO slices. Supplementing incubation medium during recovery with 20 mM D-glucose normalized glycogen replenishment but had no effect on recovery of synaptic function. In contrast, 20 mM non-metabolizable L-glucose substantially improved recovery of synaptic function, suggesting that D-glucose metabolism contributes to the excitotoxic injury in the synGLT-1 KO slices. L-lactate substitution for D-glucose did not promote recovery of synaptic function, implicating mitochondrial metabolism. Consistent with this hypothesis, phosphorylation of pyruvate dehydrogenase, which decreases enzyme activity, was increased in WT slices during the recovery period, but not in synGLT-1 KO slices. Since metabolism of glucose by the mitochondrial electron transport chain is associated with superoxide production, we tested the effect of drugs that scavenge and prevent superoxide production. The superoxide dismutase/catalase mimic EUK-134 conferred complete protection and full recovery of synaptic function. A site-specific inhibitor of complex III superoxide production, S3QEL-2, was also protective, but inhibitors of NADPH oxidase were not. In summary, we find that the failure of recovery of synaptic function in hippocampal slices from the synGLT-1 KO mouse, previously shown to be due to excitotoxic injury, is caused by production of superoxide by mitochondrial metabolism.

The Role and Mechanism of Probiotics Supplementation in Blood Glucose Regulation: A Review.

With economic growth and improved living standards, the incidence of metabolic diseases such as diabetes mellitus caused by over-nutrition has risen sharply worldwide. Elevated blood glucose and complications in patients seriously affect the quality of life and increase the economic burden. There are limitations and side effects of current hypoglycemic drugs, while probiotics, which are safe, economical, and effective, have good application prospects in disease prevention and remodeling of intestinal microecological health and are gradually becoming a research hotspot for diabetes prevention and treatment, capable of lowering blood glucose and alleviating complications, among other things. Probiotic supplementation is a microbiologically based approach to the treatment of type 2 diabetes mellitus (T2DM), which can achieve anti-diabetic efficacy through the regulation of different tissues and metabolic pathways. In this study, we summarize recent findings that probiotic intake can achieve blood glucose regulation by modulating intestinal flora, decreasing chronic low-grade inflammation, modulating glucagon-like peptide-1 (GLP-1), decreasing oxidative stress, ameliorating insulin resistance, and increasing short-chain fatty acids (SCFAs) content. Moreover, the mechanism, application, development prospect, and challenges of probiotics regulating blood glucose were discussed to provide theoretical references and a guiding basis for the development of probiotic preparations and related functional foods regulating blood glucose.