Medicine Research Research Articles

Investigation of the mechanism of nephrotoxicity of nux-vomica by PTGS2/CYP2C9-mediated arachidonic acid pathway and Jian Pi Tong Luo compound's protective effect.

The clinical effectiveness of nux-vomica in treating rheumatism and arthralgia is noteworthy; however, its nephrotoxicity has sparked global concerns. Hence, there is value in conducting studies on detoxification methods based on traditional Chinese medicine compatibility theory. Blood biochemistry, enzyme-linked immunosorbent assay, and pathological sections were used to evaluate both the nephrotoxicity of nux-vomica and the efficacy of the Jian Pi Tong Luo (JPTL) compound in mitigating this toxicity. Kidney metabolomics, using ultra-high-performance liquid chromatography-quadrupole-time-of-flight-MS (UPLC-Q-TOF-MS), was applied to elucidate the alterations in small-molecule metabolites in vivo. In addition, network pharmacology analysis was used to verify the mechanism and pathways underlying the nephrotoxicity associated with nux-vomica. Finally, essential targets were validated through molecular docking and western blotting. The findings indicated significant nephrotoxicity associated with nux-vomica, while the JPTL compound demonstrated the ability to alleviate this toxicity. The mechanism potentially involves nux-vomica activating the "PTGS2/CYP2C9-phosphatidylcholine-arachidonic acid metabolic pathway." This study establishes a scientific foundation for the clinical use of nux-vomica and lays groundwork for further research and safety assessment of toxic Chinese herbal medicines.

Research progress in psychosomatic medicine in 2023: An overview

Psychosomatic medicine focuses on exploring the interactions of biological, psychological, and social factors in regulating the balance between health and disease. Recent shifts in disease spectra and medical models have contributed to the heightened prevalence and burden of psychosomatic diseases, posing new challenges to the contemporary health-care system. Consequently, there has been an imperative drive toward intensified research in psychosomatic medicine. Neuroscience methodologies have been widely applied in the research of psychosomatic diseases, facilitating the exploration of underlying causal mechanisms of psychosomatic diseases and the examination of correlations between brain function, specific organ systems, and clinical manifestations. This article offers a review of the contemporary research developments in 2023 regarding the pathogenesis, diagnosis, treatment, and intervention strategies for psychosomatic diseases, approached from various systemic perspectives. Drawing upon these insights, it offers an outlook on the future of psychosomatic medicine, aiming to enhance the integration of body–mind to clinical practice for the management of psychosomatic diseases.

Role of Herbal Active Compound in Cardiac Failure Treatment

The prevalence of cardiovascular diseases (CVDs) is constantly rising, making them a major health burden. In terms of global mortality and morbidity, they are still at the top. An alternate method of treating many illnesses, including CVDs, is the use of medicinal herbs. There is a current, unprecedented push to include herbal remedies into contemporary healthcare systems. The widespread conviction in their safety and the fact that they offer more effective treatment at a lower cost than conventional modern medicines are two of the main factors propelling this movement. However, there has not been enough testing of the purported safety of herbal remedies. As a result, people need to know that medical herbs can be toxic, have possibly fatal side effects, and can interact negatively with other drugs. Experimental evidence suggests that medicinal herbs may be useful in the treatment of cardiovascular diseases (CVDs) due to their ability to inhibit multiple risk factors for these conditions. So, in order to successfully use herbs in CVD therapy, there have been numerous initiatives to transition medicinal herb research from the lab to the clinic. Presented below are cardiovascular diseases (CVDs) and the variables that put people at risk for developing them. Next, we provide a synopsis of herbal medicine's role in the treatment of disease, with a focus on cardiovascular diseases. In addition, information is compiled and examined about the ethnopharmacological therapeutic possibilities and medicinal qualities against cardiovascular diseases of four commonly used plants: ginseng, gingko biloba, ganoderma lucidum, and gymnostemma pentaphyllum. The use of these four plants in the treatment of cardiovascular diseases (CVDs) including myocardial infarction, hypertension, peripheral vascular disorders, coronary heart disease, cardiomyopathies, and dyslipidemias has been well examined. We are also making an effort to describe the current in vitro and in vivo investigations that have attempted to examine the cellular and molecular underpinnings of the four plants' cardio-protective effects. Lastly, we highlighted the effectiveness, safety, and toxicity of these four medicinal herbs by reviewing and reporting the results of current clinical trials.
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A comparative study of Fe (II) doped chiral L/D-methionine carbon dots (MCDs) as a “Turn-on” fluorescent probe for the sensitive detection of L – cysteine

Chiral carbon dots have prominently influenced in the field of chemical, biological, and medicinal research. Comparing to achiral carbon dots, chiral carbon dots exhibit unique characteristics in biosensing application. In this perspective, we have developed bright blue, fluorescent L and d-Methionine Chiral carbon dots (MCDs) using a simple microwave assisted process for effective sensing of l-Cysteine. l-Cysteine plays a vital role in balancing the physiological redox in the body. These MCDs can be complexed with Fe2+ ions to create an energy transfer quenching system due to distinctive N and S functional group distribution on their surface. However, l-Cysteine attaches to Fe2+ ions in a competitive manner, leads to recovery of MCDs fluorescence. As a result, a "turn-on" fluorescent sensing platform based on L and d-Methionine-CDs has been developed for the rapid identification and detection of l-Cysteine. The probe shows good selectivity and sensitivity with coexisting biomolecules and ions. From comparative PL studies, d- MCDs are more responsive than l-Meth CDs towards the detection of l-cysteine with LOD of 0.71 µM and 0.94 µM respectively. The chiroptical properties were evaluated and the probe extends its practical application in paper strip and in biological matrix such as human blood serum with satisfactory recoveries in the range 85–104%.

The complete Chloroplast genome of Stachys geobombycis and comparative analysis with related Stachys species

Herb genomics, at the forefront of traditional Chinese medicine research, combines genomics with traditional practices, facilitating the scientific validation of ancient remedies. This integration enhances public understanding of traditional Chinese medicine’s efficacy and broadens its scope in modern healthcare. Stachys species encompass annual or perennial herbs or small shrubs, exhibiting simple petiolate or sessile leaves. Despite their wide-ranging applications across various fields, molecular data have been lacking, hindering the precise identification and taxonomic elucidation of Stachys species. To address this gap, we assembled the complete chloroplast (CP) genome of Stachys geobombycis and conducted reannotation and comparative analysis of seven additional species within the Stachys genus. The findings demonstrate that the CP genomes of these species exhibit quadripartite structures, with lengths ranging from 14,523 to 150,599 bp. Overall, the genome structure remains relatively conserved, hosting 131 annotated genes, including 87 protein coding genes, 36 tRNA genes, and 8 rRNA genes. Additionally, 78 to 98 SSRs and long repeat sequences were detected , and notably, 6 highly variable regions were identified as potential molecular markers in the CP genome through sequence alignment. Phylogenetic analysis based on Bayesian inference and maximum likelihood methods strongly supported the phylogenetic position of the genus Stachys as a member of Stachydeae tribe. Overall, this comprehensive bioinformatics study of Stachys CP genomes lays the groundwork for phylogenetic classification, plant identification, genetic engineering, evolutionary studies, and breeding research concerning medicinal plants within the Stachys genus.

Social, Ethical and Regulatory implications of conducting a malaria Vaccine Efficacy trial in a human infection study in Kenya (SERVE-Kenya): A study protocol

Malaria remains an important public health problem in many LMICs, including Kenya – necessitating alternative prevention and control strategies. Malaria human infection studies (HIS) – trials that involve the deliberate infection of healthy volunteers with malaria parasites to assess the efficacy of potential vaccine and drug candidates and to understand the innate and acquired protection against malaria parasites - have become an important approach to fast-track the development of a malaria vaccine. The KEMRI-Wellcome Trust Research Programme (KWTRP) otherwise known as the KEMRI Centre for Geographic Medicine Research (Coast) (KEMRI CGMRC) has developed expertise in setting up and running research on malaria HIS, with two completed and two planned in the coming months. One of the planned studies is an EDCTP-funded Phase IIb malaria vaccine efficacy trial within a HIS. While all scientific proposals at KWTRP are carefully reviewed by national and international science and ethics review bodies and are supported by a well-developed local community engagement platform, research to understand the social, ethical and regulatory issues for HIS from a grounded perspective is in early stages of development, especially in LMICs. Given the particular opportunities provided by the KWTRP’s experience in running HIS, expertise in embedded social science research and the presence of a well-established community engagement platform, we plan to conduct a social science study within the HIS-based Phase IIb malaria vaccine trial. The overall aim is to contribute to the development of locally responsive policies on the ethical conduct of malaria vaccine efficacy studies involving the use of a HIS in Kenya. Data will be collected from a range of HIS stakeholders, including HIS participants, community members, HIS research team, ethics committees, regulatory authorities and policy makers through surveys, interviews, group discussions, participatory workshops, observations and document review. This is an EDCTP-funded Career Development Fellowship project awarded to PCC.

Exploring the phytochemical and biological properties of Salsola foetida: a promising wild plant from Southeastern Algeria

ABSTRACT This study presents an initial exploration of the phytochemical composition and biological properties of Salsola foetida, a wild plant native to southeastern Algeria. The investigation encompassed an analysis of the biochemical content, phytochemical profile, and bioactivity of the plant’s aerial parts. The biomass of S. foetida was found to comprise 51.2 ± 0.4% ash, with elemental analysis revealing the presence of carbon, oxygen, calcium, sodium, chlorine, magnesium, potassium, and sulfur. Carbohydrates were identified as the predominant constituents, surpassing the levels of proteins and lipids. Phytochemical screening, coupled with Fourier Transform Infrared (FT-IR) analysis, confirmed the presence of various secondary metabolites, including alkaloids and phenols. Reversed-phase high-performance liquid chromatography (RP-HPLC) analysis further delineated a spectrum of phenolic compounds, with rutin emerging as the predominant compound at 1.59 µg/ml. Quantification revealed a noteworthy phenolic content of 67.1 ± 0.2 µg GE/mg ED. The extract exhibited robust radical scavenging effects, with the radical 50% inhibitory concentration (IC50) being 61.8 ± 0.2 μg/ml, along with protective effects against H2O2-induced hemolysis and the ability to reduce ferric ions. Additionally, the extract demonstrated anti-inflammatory, antibacterial, and antidiabetic activities. Notably, it exhibited considerable sunscreen properties, boasting a sun protected factor (SPF) value of 21 ± 1. Overall, S. foetida presents promising antioxidant activity and a spectrum of potential biological activities, underscoring its significance as a novel antioxidant candidate for applications in animal nutrition, medicine, and natural product research.

Magnetic beads and GO-assisted enzyme-free signal amplification fluorescent biosensors for disease diagnosis

Cancer detection is still a major challenge in public health. Identification of oncogene is the first step toward solving this problem. Studies have revealed that various cancers are associated with miRNA expression. Therefore, the sensitive detection of miRNA is substantially important to solve the cancer problem. In this study, let-7a, a representative substance of miRNA, was selected as the detection target. With the assistance of magnetic beads commonly used in biosensors and self-synthesized graphene oxide materials, specificity and sensitivity detection of the target gene let-7a were achieved via protease-free signal amplification. The limit of detection (LOD) was as low as 15.015pM. The fluorescence signal intensity showed a good linear relationship with the logarithm of let-7a concentration. The biosensor could also detect let-7a in complex human serum samples. Overall, this fluorescent biosensor is not only simple to operate, but also strongly specificity to detect let-7a. Therefore, it has substantial potential for application in the early diagnosis of clinical medicine and biological research.

Harnessing Nature's Pharmacy: Biotechnology Advances in Medicinal Plant Research

The integration of biotechnology into medicinal plant research has revolutionized the pharmaceutical industry, offering unprecedented opportunities for the development of novel therapeutics and healthcare solutions. By tapping into the vast biochemical diversity of plants, scientists have unlocked a treasure trove of potential drug candidates, many of which have been used in traditional medicine for centuries. Biotechnological tools such as genetic engineering, tissue culture, metabolomics, and bioinformatics have enabled the precise manipulation and optimization of plant-derived compounds, leading to the production of high-value pharmaceuticals with enhanced efficacy and safety profiles. Moreover, biotechnology facilitates sustainable practices by enabling the cultivation of medicinal plants under controlled conditions, reducing reliance on wild harvesting and alleviating pressure on endangered species. As our understanding of plant biology continues to deepen, the synergy between biotechnology and medicinal plant research holds tremendous promise for addressing global health challenges and improving patient outcomes.

Novel Tetracyclic Azaphenothiazines with the Quinoline Ring as New Anticancer and Antibacterial Derivatives of Chlorpromazine.

Phenothiazine derivatives are widely studied in various fields such as biology, chemistry, and medicine research because of their pharmaceutical effects. The first compound used successfully in the treatment of psychosis was a phenthiazine derivative, chlorpromazine. Apart from its activity in neurons, chlorpromazine has also been reported to display anticancer and antibacterial properties. In this study, we present the synthesis and research on the activity of A549, MDA, MiaPaCa, PC3, and HCT116 cancer cell lines and of S. aureus, S. epidermidis, E. coli, and P. aeruginosa bacterial strains against a series of new tetracyclic chlorpromazine analogues containing a quinoline scaffold in their structure instead of the benzene ring and various substituents at the thiazine nitrogen. The structure of these novel molecules has been determined by 1H NMR, 13C NMR, and HRMS spectral techniques. The seven most active of the twenty-four new chlorpromazine analogues tested were selected to study the mechanism of cytotoxic action. Their ability to induce apoptosis or necrosis in cancer cells was assessed by flow cytometry analysis. The results obtained confirmed the proapoptotic activity of selected compounds, especially in terms of inducing late apoptosis or necrosis in cancer cell lines A549, MiaPaCa-2, and HCT-116. Furthermore, studies on the induction of cell cycle arrest suggest that the new chlorpromazine analogues exert antiproliferative effects by inducing cell cycle arrest in the S phase and, consequently, apoptosis.

Selection of Leptin Surrogates by a General Phenotypic Screening Method for Receptor Agonists.

There is a high demand for agonist biomolecules such as cytokine surrogates in both biological and medicinal research fields. These are typically sourced through natural ligand engineering or affinity-based screening, followed by individual functional validation. However, efficient screening methods for identifying rare hits within immense libraries are very limited. In this research article, we introduce a phenotypic screening method utilizing biological receptor activation-dependent cell survival (BRADS). This method offers a high-throughput, low-background, and cost-effective approach that can be implemented in virtually any biochemical laboratory setting. As a proof-of-concept, we successfully identified a surrogate for human leptin following a two-week cell culture process, without the need for specialized high-throughput equipment or reagents. This surrogate effectively emulates the activity of native human leptin in cell validation assays. Our findings not only underscore the effectiveness of BRADS but also suggest its potential applicability to a broad range of biological receptors, including Notch and GPCRs.

Cannabis medicine for chronic pain

In the last decade, patients with chronic pain have expressed increasing interest in cannabis-derived products for adjuvant therapy when treatment is deemed refractory to conventional analgesics. At present, clinical evidence to support this treatment approach appears to be sparse. Not because clinical studies as such are lacking, but rather as a result of methodological bias in relation to study design, patient populations, and treatment protocols. In this review, research in cannabis medicine for relief of chronic pain is reviewed, mainly with reference to published meta-analytic studies.

Patient-derived tumor-like cell clusters for personalized chemo- and immunotherapies in non-small cell lung cancer

Many patient-derived tumor models have emerged recently. However, their potential to guide personalized drug selection remains unclear. Here, we report patient-derived tumor-like cell clusters (PTCs) for non-small cell lung cancer (NSCLC), capable of conducting 100-5,000 drug tests within 10days. We have established 283 PTC models with an 81% success rate. PTCs contain primary tumor epithelium self-assembled with endogenous stromal and immune cells and show a high degree of similarity to the original tumors in phenotypic and genotypic features. Utilizing standardized culture and drug-response assessment protocols, PTC drug-testing assays reveal 89% overall consistency in prospectively predicting clinical outcomes, with 98.1% accuracy distinguishing complete/partial response from progressive disease. Notably, PTCs enable accurate prediction of clinical outcomes for patients undergoing anti-PD1 therapy by combining cell viability and IFN-γ value assessments. These findings suggest that PTCs could serve as a valuable preclinical model for personalized medicine and basic research in NSCLC.

Phytochemical analysis and acute toxicity of Solanum elaeagnifolium extract in Swiss albino mice

IntroductionThe curative effects of Solanum elaeagnifolium have aroused the interest of botanical medicine researchers. However, no research has been carried out into its potential toxicity. The aim of this study was firstly to screen the secondary metabolites contained in the leaves and fruits of S. elaeagnifolium and their mineralogical composition, and secondly to assess the acute oral toxicity of S. elaeagnifolium in Swiss albino mice. MethodsThe amount of minerals in the plant powder was assessed by inductively coupled plasma atomic emission spectrometry, and phytochemical screening was performed. The hydroethanolic extracts of the leaves and fruits of this plant were prepared using the maceration method. Acute oral toxicity was assessed according to the OECD guideline 423. Mice were given leaf extracts (SEFE) and fruit extracts (SEFR) once at doses of 500 mg/kg, 1000 mg/kg and 2000 mg/kg in an acute toxicity study. The animals were then monitored for 14 days. The animals were then monitored for 14 days. To rule out any potential toxicity, the general behavior of the animals, the clinical symptoms of poisoning, body weight, biochemical and hematological markers, and liver, kidney, and spleen histology were examined. ResultsThe two different plant extracts comprised very important mineralogical elements such as Mg, Zn, and k, as well as secondary metabolites such as polyphenols and flavonoids, these chemical elements were shown to have very important biological activities. An oral administration of a hydroethanolic extract of S. elaeagnifolium leaves and fruits at a dose of 2000 mg/kg resulted in toxicity and death in mice. We found no significant difference in the weight of the mice. For doses less than 2000 mg/kg, biochemical markers in the liver, kidneys, and hematology did not differ significantly from those in the control group. Furthermore, there were no changes in hematological markers. Furthermore, the architecture of the liver, spleen, and kidney was normal and histopathological analysis did not reveal significant adverse effects. ConclusionsThese findings indicate that the plant harbors a significant array of secondary metabolites and minerals. S. elaeagnifolium exhibited signs of toxicity and induced histological, hematological, and biochemical alterations at a dose of 2000 mg/kg body weight. These comprehensive studies will help to improve our understanding of S. elaeagnifolium safety and potential utility, laying the groundwork for its safe use in a variety of settings.

IMPLEMENTATION OF PATIENT-CENTERED MEDICAL CARE MODEL: ANALYSIS OF THE ATTITUDES OF PATIENTS WITH CORONARY ARTERY DISEASE AND COMORBIDITIES

The aim: to evaluate the attitude of patients with coronary artery disease and comorbidities to the implementation of patient-centered care in clinical practice.
 Materials and methods. We carried out questionnaire survey of two groups of patients with coronary artery disease and comorbidities. The first one consisted of 30 patients with coronary artery disease aged 61-75 (mean age 67,2±5,1 years) who were followed by the cardiologist in the therapeutic department of the State Institution of Sciences “Research and Practical Center of Preventive and Clinical Medicine” State Administrative Department. The second one – 33 military personnel with coronary artery disease aged 50-58 years (mean age 53,2±2,4 years) who came for a scheduled appointment with a general practitioner at the Outpatient Care Clinic of the National military medical clinical center “GVKG”. Methods: system analysis, questionnaire survey, statistical.
 Results. According to patient`s opinion cardiologists give much more information about pharmacological treatment, including side effects of medications used (83,3±6,8% in the Ist group vs 33,3±8,2% in the 2nd group, p<0,05) and actions to increase patients` compliance (83,3±6,8% in the Ist group vs 42,4± 8,6% in the 2nd group, p<0,05). This is related to the peculiarities of management of patients with chronic diseases in the State Institution of Science “Research and Practical Center of Preventive and Clinical Medicine” State Administrative Department, in particular, with the follow-up of high-risk cardiac patients, including scheduled appointments and monitoring of patient`s clinical conditions by a cardiologist. Emotional support was given to 93,3±4,6% of patients in the Ist group and to 18,2±6,7% of patients in the 2nd group (p<0,05). 36,7±8,8% of patients in the Ist group and 84,8±6,3% in the 2nd group ( p<0,05) indicated, that they need more information about their treatment plan and involvement in clinical decision-making. 93,3±4,6% of patients in the Ist group and 4,8±6,3 % in the 2nd group were ready to perform self-monitoring of their health conditions and participate in the decision-making process regarding their treatment.
 Conclusions. Our survey demonstrated, that the majority of interviewed patients with coronary artery disease and comorbidities are ready to use basic principles of patient-centered care. The necessity to improve patient`s information and education about clinical decision-making and physician`s practical skills in the field of implementation of patient-centered care was substantiated.

New Salicylanilide Derivatives and Their Peptide Conjugates as Anticancer Compounds: Synthesis, Characterization, and In Vitro Effect on Glioblastoma.

Pharmacologically active salicylanilides (2-hydroxy-N-phenylbenzamides) have been a promising area of interest in medicinal chemistry-related research for quite some time. This group of compounds has shown a wide spectrum of biological activities, including but not limited to anticancer effects. In this study, substituted salicylanilides were chosen to evaluate the in vitro activity on U87 human glioblastoma (GBM) cells. The parent salicylanilide, salicylanilide 5-chloropyrazinoates, a 4-aminosalicylic acid derivative, and the new salicylanilide 4-formylbenzoates were chemically and in vitro characterized. To enhance the internalization of the compounds, they were conjugated to delivery peptides with the formation of oxime bonds. Oligotuftsins ([TKPKG]n, n = 1-4), the ligands of neuropilin receptors, were used as GBM-targeting carrier peptides. The in vitro cellular uptake, intracellular localization, and penetration ability on tissue-mimicking models of the fluorescent peptide derivatives were determined. The compounds and their peptide conjugates significantly decreased the viability of U87 glioma cells. Salicylanilide compound-induced GBM cell death was associated with activation of autophagy, as characterized by immunodetection of autophagy-related processing of light chain 3 protein.

Consumption of dietary fiber and APOA5 genetic variants in metabolic syndrome: baseline data from the Korean Medicine Daejeon Citizen Cohort Study

BackgroundConsumption of dietary fiber has been suggested as an important aspect of a healthy diet to reduce the risk of metabolic syndrome (MetS), including cardiovascular disease. The role of fiber intake in MetS might differ by individual genetic susceptibility. APOA5 encodes a regulator of plasma triglyceride levels, which impacts the related mechanisms of MetS. This study investigated the association between dietary fiber and the risk of MetS, assessing their associations according to APOA5 genetic variants.MethodsA total of 1985 participants aged 30–55 years were included from a cross-sectional study based on the Korean Medicine Daejeon Citizen Cohort study at baseline (2017–2019). Dietary fiber intake was measured using a semiquantitative food frequency questionnaire. The APOA5 polymorphisms (rs2266788 A > G, rs662799 A > G, and rs651821 T > C) were genotyped using the Asia Precision Medicine Research Array. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs).ResultsA higher consumption of dietary fiber was associated with a lower prevalence of MetS (P = 0.025). Among the components of MetS, an inverse association with dietary fiber was observed in increased waist circumference (OR, 95% CI = 0.60, 0.41–0.88, P for trend = 0.009) and elevated triglycerides (OR, 95% CI = 0.69, 0.50–0.96, P for trend = 0.012). Regarding the interaction with APOA5 genetic variants, a stronger association with dietary fiber intake was shown in G allele carriers of rs662799 than in A/A carriers (OR, 95% CI = 2.34, 1.59–3.44, P for interaction = 0.024) and in C allele carriers of rs651821 than in T/T carriers (OR, 95% CI = 2.35, 1.59–3.46, P for interaction = 0.027).ConclusionsThe findings of this study suggest that the benefits of dietary fiber on the risk of MetS could be modified by genetic variants of the APOA5 gene, providing a more effective strategy for preventing MetS.

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights.

Theophylline, a nitrogen-containing heterocycle, serves as a promising focal point for medicinal researchers aiming to create derivatives with diverse pharmacological applications. In this work, we present an improved synthetic method for a range of theophylline-1,2,4-triazole-S-linked N-phenyl acetamides (4a‒g) utilizing ultrasound-assisted synthetic approach. The objective was to assess the effectiveness of synthesized theophylline-1,2,4-triazoles (4a‒g) as inhibitors of HCV serine protease and as antibacterial agents against B. subtilis QB-928 and E. coli AB-274. Theophylline-1,2,4-triazoles were obtained in good to excellent yields (69%-95%) in a shorter time than conventional approach. 4-Chlorophenyl moiety containing theophylline-1,2,4-triazole 4c displayed significantly higher inhibitory activity against HCV serine protease enzyme (IC50 = 0.015 ± 0.25mg) in comparison to ribavirin (IC50 = 0.165 ± 0.053mg), but showed excellent binding affinity (-7.55kcal/mol) with the active site of serine protease, better than compound 4c (-6.90kcal/mol) as well as indole-based control compound 5 (-7.42kcal/mol). In terms of percentage inhibition of serine protease, 2-chlorophenyl compound 4b showed the maximum percentage inhibition (86%), more than that of the 3,4-dichlorophenyl compound 4c (76%) and ribavirin (81%). 3,4-Dimethylphenyl-based theophylline-1,2,4-triazole 4g showed the lowest minimum inhibitory concentration (MIC = 0.28 ± 0.50μg/mL) against the B. subtilis bacterial strain as compared to the standard drug penicillin (MIC = 1 ± 1.50μg/mL). The other 4-methylphenyl theophylline-1,2,4-triazole 4e (MIC = 0.20 ± 0.08μg/mL) displayed the most potent antibacterial potential against E. coli in comparison to the standard drug penicillin (MIC = 2.4 ± 1.00μg/mL). Molecular docking studies further helped in an extensive understanding of all of the interactions between compounds and the enzyme active site, and DFT studies were also employed to gain insights into the molecular structure of the synthesized compounds. The results indicated that theophylline-linked triazole derivatives 4b and 4c showed promise as leading contenders in the fight against the HCV virus. Moreover, compounds 4e and 4g demonstrated potential as effective chemotherapeutic agents against E. coli and B. subtilis, respectively. To substantiate these findings, additional in vivo studies and clinical trials are imperative, laying the groundwork for their integration into future drug design and development.

Association of single nucleotide polymorphism rs3213119 variant of IL-12B gene in diagnosed Rheumatoid Arthritis patients.

To identify the IL12B gene variant (rs3213119) and to find its association in Pakistani clinical population of Rheumatoid Arthritis. It was a population association (unrelated) case control study, performed from January - December 2022 at Laboratory of Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi. Blood samples were collected from all 150 study participants, followed by DNA extraction and Allele-specific polymerase chain reaction performed at Center for Research in Experimental and Applied Medicine (CREAM) Laboratory of Department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi. Statistical analysis was done using 'SPSS' (version-22), followed by gene analysis on 'SNPstat'. About 28.0% of RA patients were smokers, 38.7% had history of RA in a first degree relative and 70.7% had positive history of consanguinity. Considering rs3213119 variant of IL12B gene, frequency of major allele C was 100%, minor allele A was 21%, genotype C/C was 79% and C/A was 21%. Applying the log additive model, the odds ratio of the genotype C/C was 1.00 (adjusted by age and gender with 95 % CI) and the odds ratio of the genotype C/A was 0.00, 52.0% of RA patients originated from four predominant ethnic groups, namely Awaans (18.7%), Rajputs (14.7%), Pathans (12.0%) and Araeens (6.7%). The study findings suggest the role of minor allele 'A' as risk allele in our clinical population. CA genotype confers susceptibility towards the RA development.

Exploring the Regulatory Mechanism of ZnS Materials under Stress and Re Doping: Insights from Density Functional Theory

The application prospects of ZnS stress luminescent materials cover many fields such as high‐precision structural monitoring, smart materials, biomedical imaging, and new sensor technologies, which bring broad application prospects and significance to them in the fields of engineering, medicine, and scientific research. In this article, the electronic structure and optical properties of ZnS materials are successfully regulated by applying pressure and doping rare earth metals (Re), and it is found that the regulation of the luminescence properties of ZnS is the result of stress and doping interactions. Specifically, when pressure is applied or Re metal doping, the lattice structure is deformed and the atomic spacing is adjusted, which affects the electronic energy level distribution and optical properties of ZnS materials. Computational analysis of density functional theory (DFT) reveals the microscopic mechanisms behind these changes, including changes in lattice parameters, adjustment of bond length, and changes in band structure. This study provides theoretical guidance for the design and synthesis of high‐performance and high‐stability ZnS light‐emitting materials, and is of great significance for expanding the application of ZnS in the field of lasers and sensors.