Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology最新文献

Epigenetic mechanisms-DNA methylation, histone modifications, and non-coding RNAs-integrate genetic programs with environmental cues to shape neural development, plasticity, and pathology. During neurogenesis, methylation patterns and histone marks direct stem cell fate and synapse formation, while microRNAs fine-tune gene expression. In the adult brain, rapid, reversible histone acetylation and activity-dependent non-coding RNAs underlie learning, memory, and injury responses. Environmental stressors, toxins, and diet can trigger maladaptive epigenetic changes, linking exposures to cognitive deficits and psychiatric risk. Aberrant methylation and histone landscapes are implicated in autism, Alzheimer's, and Parkinson's-altering synaptic scaffolding, amyloid processing, and neuronal survival-while dysregulated microRNAs serve as both biomarkers and intervention targets. Advances in single-cell methylome sequencing, ChIP-seq, and multi-omics are clarifying cell-type specificity, and emerging therapies (HDAC inhibitors, methyl donors, RNA-based tools) offer promise, pending precise delivery and safety optimizations.

Background: Dapagliflozin is used for controlling blood glucose levels in patients with type 2 diabetes. It is a sodium-glucose cotransporter 2 inhibitor, which enhances the elimination of blood glucose through the urine by inhibiting the protein involved in the transport mechanism of SGLT2. Dapagliflozin requires a selective and sensitive bioanalytical RP-HPLC method.

Aim: Reverse phase - high performance liquid chromatography technique was used to develop and validate a bioanalytical method for the quantification of dapagliflozin (DAPA) in human plasma.

Methods: The internal standard (IS) used was azilsartan medoxomil. In isocratic mode, the mobile phase consisted of 50:50 v/v acetonitrile and 0.1% orthophosphoric acid in water at a flow rate of 1.0 mL/min. The chromatogram was recorded at 224 nm. For the chromatographic separation, a Kromasil C18 column (250 mm × 4.6 mm; 5μ) was used. The drug was extracted from plasma samples by the protein precipitation method.

Result and discussion: The chromatographic run time was 15 min. Dapagliflozin and IS eluted at 4.6 and 5.7 min, respectively. The method was selective and sensitive, with a limit of quantification of 1.50 µg/mL. The developed method was found to be linear in the range of 1.50-60 µg/mL (r2 = 0.9994). The accuracy and precision obtained from six sets of quality control (QC) samples ranged from 96.23% to 108.67% and 1.35% to 3.19%, respectively. The extraction recovery of dapagliflozin in three QC samples ranged from 87.39% to 90.78%. The bench-top stability, stock solution stability, stability of processed extracted samples at room temperature, and freeze-thaw stability evaluations showed no evidence of degradation of dapagliflozin.

Conclusion: The stability, selectivity, sensitivity, and reproducibility of the developed method make it suitable for the determination of dapagliflozin in human plasma.

Background: The clinical effectiveness of wide range of currently available anticancer drugs is being reduced .HIF-1 alpha is essential for the reprogramming of cancer cells' metabolism,so cancer treatments include inhibiting the HIF-1α signaling pathway and The evidence underscores the potential of natural flavonoids as HIF-1α inhibitors in cancer therapy.

Objective: To provide more comprehensive overview of inhibition of flavonoids on HIF-1 which may be useful for developing new compounds with enhanced anticancer properties and also to provide reasearchers with a thought to design potent and low toxic anticancer candidates.

Material and methods: A comprehensive review of recent literature was conducted to identify studies investigating the effects of natural flavonoids and their derivatives on HIF-1α activity. Emphasis was placed on mechanisms of action, efficacy, and toxicity profiles, as well as their impact on tumor hypoxia and associated pathways such as vascularization and glycolysis.

Result: Recent findings demonstrate that various natural flavonoids effectively downregulate HIF-1α through distinct mechanisms. These compounds exhibit significant anti-cancer properties while maintaining low toxicity, making them viable candidates for further development. Several studies have also highlighted the ability of flavonoids to influence tumor vascularization and glycolytic pathways, thereby enhancing their therapeutic potential.

Conclusion: In this review in order to increase bioavailability , solubility and to better understand the impact of anticancer flavonoids on HIF-1 alpha, amino acids or amino groups were added to the flavonoid structure. understanding the effect of anticancer flavonoids on HIF-1 α may be relevant in the development of novel compounds with increased anticancer activity.

Acute Myeloid leukemia (AML) is a genetically heterogeneous hematologic malignancy that disproportionately affects older individuals. Among the various genetic alterations, FLT3 internal tendem duplication (FLT3-ITD) mutations are present in approximately 20-30% of patients and are linked to rapid disease progression and frequent relapses. This review evaluates the role of quizartinib, a second-generation, highly selective FLT3 inhibitor, as a targeted therapeutic option for relapsed or refractory AML. Preclinical studies have demonstrated that quizartinib offers potent inhibition of FLT3 signaling, favorable pharmacokinetic properties, and high bioavailability. Early-phase clinical trials reported promising remission rates in patients harboring FLT3-ITD mutations, while phase III studies further substantiated its efficacy by showing improved overall survival when used alone or alongside standard chemotherapy. Despite these advances, quizartinib's clinical use is limited by challenges such as acquired resistance, off-target effects-including QT interval prolongation-and complex drug-drug interactions. Ongoing research is focused on elucidating resistance mechanisms and developing effective combination regimens to optimize its therapeutic potential. Overall, quizartinib represents a significant breakthrough in precision medicine for AML, offering a promising avenue to improve patient outcomes in this challenging disease.

Purpose: Nanogels (NGs) represent a new generation of nanoscale hydrogel particles with immense biomedical applications, especially drug delivery System (DDS). Nanogels (NGs) are soft and water-retentive materials that deliver drugs in controlled and sustained release while maintaining high biocompatibility and biodegradability.

Method: This review paper primarily focuses on the applications, mechanism, therapies. The capability to react with environmental signals, such as pH, temperature, or enzymatic activity, makes nanogels a promising platform for targeted therapy. Polysaccharide-based nanogels increase biocompatibility and reduce toxicity, allowing for extended therapeutic applications.

Result: This reviews the structural properties, drug release mechanisms, and newer developments in nanogel formulations. It also presents the future outlook for nanogels in precision medicine, highlighting their potential in transcending pharmacological obstacles towards enhancing drug delivery and therapeutic efficacies in various branches of medicine.

Conclusion: By overcoming existing drawbacks, nanogels have the potential to revolutionize drug delivery and therapeutic interventions in diverse clinical settings.

Alpelisib is a cancer therapy drug that has shown significant promise in the treatment of certain types of cancer. Its pharmacokinetics and pharmacodynamics indicate that it is absorbed better orally and has a prolong half-life, allowing for once-every day dosing. Currently, its mechanism of action is established to be the suppression of phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), which is the pivotal enzyme of PI3K pathway, which is abnomal in most cancers. The chemistry of alpelisib involves its selective inhibition of PI3K, targeting specifically HR-positive, HER2-negative breast cancer with PIK3CA mutations. The common side effects associated with alpelisib include fever, peripheral edema, fatigue, headache, skin rash, alopecia, pruritis, hyperglycemia, increased gamma-glutamyl transferase, decreased serum calcium, weight loss, diarrhea, nausea, increased serum lipase, decreased appetite, stomatitis, vomiting, dysgeusia, lymphocytopenia, prolonged PTT, and increased serum creatinine. The use of alpelisib in cancer therapy is being extensively studied through various clinical trials, aiming to determine the optimal patient populations for treatment and explore alternative tumor indications and drug combine regimens.

Immunoblotting, commonly known as Western blotting, remains a pivotal technique in the identification and quantification of specific proteins, offering critical insights into antigen-antibody interactions essential for vaccine development. This mini-review highlights the evolving role of immunoblotting in modern vaccinology, focusing on its application in evaluating immune responses, verifying antigen expression, and screening candidate vaccine components. Current innovations, including enhanced detection systems, high-throughput formats, and integration with proteomics, have significantly improved the sensitivity and specificity of this method. Moreover, advancements in automation and data analysis are streamlining workflows, enabling faster and more reliable vaccine research. This review underscores the continued relevance of immunoblotting in the post-genomic era, particularly as new vaccine platforms, such as mRNA and vector-based vaccines, demand precise immunological validation.

Introduction: Lakshadi Anjana Drops, a traditional Ayurvedic ocular formulation, is designed to alleviate eye-related conditions. Composed of herbal ingredients with therapeutic properties, this study aimed to evaluate the formulation's quality, safety, and efficacy through physico-chemical, microbiological, and preclinical analysis.

Methods: Formulation was analyzed for physico-chemical parameters such as pH, refractive index, peroxide value, saponification value, and iodine value. Preclinical testing was conducted using New Zealand white rabbits, where the Draize test was used to evaluate ocular safety and carrageenan-induced ocular inflammation model was employed to assess anti-inflammatory efficacy. Histopathological analysis of ocular tissues was performed to assess potential tissue damage.

Results: pH of Lakshadi Anjana Drops was found to be 7.82, confirming its suitability for ocular use. Physico-chemical parameters, including refractive index (1.4542), peroxide value (2.18 meq/kg), saponification value (210), and iodine value (38.49), were within acceptable limits, ensuring stability. Preclinical results indicated minimal ocular irritation and significant anti-inflammatory activity, comparable to a marketed formulation. Histopathological analysis showed minimal epithelial thickening, with no significant tissue damage.

Conclusion: Lakshadi Anjana Drops exhibited strong physico-chemical stability, and biocompatibility, supporting its therapeutic potential for ocular applications. The combination of traditional Ayurvedic ingredients with modern scientific validation highlights its promise for clinical use in ocular therapeutics.

The aim of this study is to explore and evaluate recent innovations in drug delivery systems (DDS) for biologics, focusing on enhancing stability and targeted delivery to improve the efficacy and safety of next-generation therapeutics. The most recent developments in a variety of DDS, such as nanoparticles, microneedles, hydrogels, and biodegradable polymers, were examined in depth. Information from peer-audited diaries, clinical preliminaries, and mechanical reports were blended to survey the presentation of these frameworks concerning dependability, designated conveyance, patient consistence, and controlled discharge. A radar chart was used in a comparative analysis to show the advantages and disadvantages of each DDS. Utilizing cutting-edge DDS, our analysis revealed significant improvements in the stability and targeted delivery of biologics. Nanoparticles exhibited the most elevated precision in designated conveyance at 92% and showed a 85% improvement in soundness. With an 88% satisfaction rate and moderate improvements in other criteria, microneedles achieved the highest level of patient compliance. Biodegradable polymers provided a balanced enhancement across all criteria, with 88% improvements in stability, 87% improvements in targeted delivery, and 89% improvements in controlled release for hydrogels. Nanoparticles lost only 6% of their stability, microneedles lost 10% of their controlled release, hydrogels lost 7% of their stability, and biodegradable polymers lost 5% of their patient compliance across all of these systems. The stability and precise delivery of biologics have been significantly improved by advancements in drug delivery systems. Hydrogels and microneedles, on the other hand, provide advantages in controlled release and patient compliance. Biodegradable polymers and nanoparticles are promising for maintaining drug integrity and targeting particular sites. In order to overcome the limitations that exist currently and enhance the therapeutic outcomes of biologics, future research ought to concentrate on hybrid strategies that combine the advantages of multiple DDS.

This study means to investigate the capability of pharmacogenetics which can customize drug treatment through altered treatment of male genetic profiles. We finished hereditary profiling utilizing cutting edge sequencing (NGS) to figure out the key hereditary varieties that impact the medications metabolic adequacy and security. Patients were checked for a very long time to evaluate clinical results including ADRs and general wellness. Hereditary assessment uncovered variations in enormous qualities, for example, CYP2C9 CYP2D6 ABCB1 VKORC1 and SLCO1B1 which assume significant parts in drug digestion and transport. These hereditary markers are related with clinical realities to evaluate their effect on drug reactions and unfriendly impacts. The outcomes recommend that customized treatment dependent exclusively upon hereditary profiles could prompt better treatment results. For instance, patients with VKORC1 changes answer better to anticoagulants and drain less while patients with SLCO1B1 transformations have statin-incited myopathy which is more expensive and requires portion changes. This mirrors the useful effect of altered treatment on wellness results. Pharmacogenomics gives a useful asset to customized medication to tailor drug medicines dependent exclusively upon a person's genetic profile.