OBJECTIVE: The objective of this study is to conduct network toxicology analysis based on smoking habits and develop a simpler and more effective toxicology product ingestion control system. BACKGROUND: Smoking behavior...OBJECTIVE: The objective of this study is to conduct network toxicology analysis based on smoking habits and develop a simpler and more effective toxicology product ingestion control system. BACKGROUND: Smoking behavior can affect the pathogenesis and prognosis of neuroimmune gastrointestinal diseases. AIMS: The purpose of developing tools to assist clinical practice is to avoid the harm of cigarettes to the human body. METHODS: Molecular dynamics method was used to elucidate the biophysical mechanism of TP53 gene mutation caused by harmful ingredients, and the signaling pathway of midbrain edge excitation was determined by molecular dynamics of nicotine and dopamine receptor D3. The possible involvement of nicotine in neuronal damage was determined through the molecular interaction between nicotine and ACHE. Molecular pathways were analyzed based on the aforementioned biological principles, developed artificial intelligence systems and brain computer interface systems. RESULTS: Several signaling pathways were elucidated, and effective AI algorithms were developed. CONCLUSION: The accuracy of artificial intelligence systems is over 70%. This study provides clinical doctors with a new precision medicine strategy and tool to regulate patient behavior and reduce disease risk. Other: This project was approved by the Ethics Committee of Chifeng Cancer Hospital and reported to the WHO.
Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's disease, represent a significant global health challenge with limited therapeutic options. Protein misfolding and aggregation, a common patho...Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's disease, represent a significant global health challenge with limited therapeutic options. Protein misfolding and aggregation, a common pathological hallmark in these disorders, have emerged as promising targets for therapeutic intervention. Molecular docking techniques have played a pivotal role in the identification and design of small molecules that can modulate protein misfolding, offering new hope for effective treatments. This review provides an overview of recent advancements in molecular docking techniques for targeting protein misfolding in neurodegenerative diseases. We discuss the principles and methodologies behind molecular docking, including various scoring functions and algorithms employed for accurate ligand-protein interactions. Additionally, we explore the use of molecular dynamics simulations and machine learning approaches to enhance the precision of docking studies. Furthermore, we highlight case studies and success stories where molecular docking has contributed to the discovery of potential drug candidates for neurodegenerative diseases. These include compounds that inhibit amyloid-β aggregation in Alzheimer's disease, α-synuclein oligomerisation in Parkinson's disease, and mutant huntingtin aggregation in Huntington's disease. We also discuss the problems and restrictions of molecular docking related to neurodegenerative diseases, such as how to accurately show the flexibility of proteins and why docking results need to be confirmed by experiments. We also discuss the structural biology methods, such as cryo-electron microscopy and X-ray crystallography, and how these techniques might help in improving molecular docking studies.
BACKGROUND: Antibiofilm agents serve as an essential tool in the fight against antibiotic resistance, and natural products provide a promising source for potential drug leads. OBJECTIVE: This study investigates the activ...BACKGROUND: Antibiofilm agents serve as an essential tool in the fight against antibiotic resistance, and natural products provide a promising source for potential drug leads. OBJECTIVE: This study investigates the activity of twenty Bangladeshi medicinal plants against and biofilms and predicts the interactions of selected phytochemicals from five of the best performing plants with the active sites of transcriptional regulatory proteins SarA of S. aureus and LasR of P. aeruginosa. METHODS: The plant extracts were tested by microtiter plate-based assay against S. aureus and P. aeruginosa biofilms. Molecular docking and molecular dynamics simulation (MD) were conducted using PyRx and GROMACS, respectively. RESULTS: The best activity was identified for and , showing ≥ 75% inhibition of biofilm formation. ent-Epicatechin-(4α→8)-epiafzelechin (EEE) of C. fistula, cyanidin-3,3',5-tri-O-β-D-glucopyranoside (CTG) of A. comosus, and 7-O-(4-hydroxy-Ecinnamoyl)- spinoside of A. spinosus showed the best predictive binding affinity (-7.6, -7.6 and - 7.7 kcal/mol, respectively) for SarA. EEE was the only ligand to exhibit a stable ligand-protein complex with SarA in the MD simulation of 200 ns (binding energy of MMPBSA analysis - 39.899 kJ/mol). Chrysophanol, epicatechin and physcion, of C. fistula (-10.5, -10.5, and -11.0 kcal/mol, respectively) and auraptene of F. limonia (-10.8 kcal/mol) showed the best predictive binding affinity for LasR. Epicatechin showed the most stable ligand-protein complex with LasR (binding energy of MMPBSA analysis -63.717 kJ/mol). CONCLUSION: Epicatechin and its derivative EEE could be used as scaffolds for the development of new antibiofilm agents against and , respectively.
AIMS: To identify potential phytochemical-based drugs for both wild-type and Omicron variants of SARS-CoV-2 using virtual screening and molecular dynamic simulation. BACKGROUND: Coronavirus disease 2019 (COVID-19) is an...AIMS: To identify potential phytochemical-based drugs for both wild-type and Omicron variants of SARS-CoV-2 using virtual screening and molecular dynamic simulation. BACKGROUND: Coronavirus disease 2019 (COVID-19) is an infectious viral disease caused by SARS-CoV-2. Since 2019, multiple variants have been reported from all over the world and the emergence of new variants of SARS-CoV-2 is a major concern. OBJECTIVE: To identify potential phytochemicals that can be used as drugs against different variants of SARS-CoV-2. METHODS: In our present study, we have selected 594 phytochemicals and performed virtual screening to identify potential drug candidates. The screening commenced with molecular docking techniques with both ACE2 (Human) and Spike protein (wild-type and Omicron variant), followed by prediction of pharmacokinetics parameters and toxicity. The Schrodinger tools, Swiss ADME, and ProTox-II accomplish the analysis. Further, molecular dynamics simulation, binding free energy calculation and meta-dynamics study was performed for best protein-ligand complexes of both proteins using GROMACS and gmx_MMPBSA to validate the stability of the docked complexes. RESULTS: we have identified 6 and 4 drugs as spike protein inhibitors for wild-type and Omicron variants, respectively. 6 drugs were identified as ACE2 receptor inhibitors. We have identified silymarin as a common drug inhibitor for both pathogen (Wild-type, and Omicrons spikes) as well as host (human ACE2) protein that reflects its ability to inhibit the host-pathogen interaction and prevent infection. CONCLUSION: We have found some potential Phytochemicals that can be used against different variants of SARS-CoV-2 such as silymarin.
Neurological illnesses encompass a broad spectrum of conditions that affect the brain, spine, and nerves, often impairing daily functioning. The global prevalence of these illnesses is rising, posing significant health c...Neurological illnesses encompass a broad spectrum of conditions that affect the brain, spine, and nerves, often impairing daily functioning. The global prevalence of these illnesses is rising, posing significant health challenges. This study investigates the beneficial effects of probiotics and postbiotics in managing various neurological disorders, providing a comprehensive analysis of their use in treating these conditions. The article explores innovative, holistic approaches to neurological care, emphasizing patient-centered therapeutic interventions. Compelling evidence suggests that probiotics and postbiotics positively impact several neurological diseases. Specifically, the findings indicate that these treatments can modulate the gut-brain axis, reduce neuroinflammation, and enhance neuronal protection. The study highlights the potential of specific bacteria and their byproducts to ameliorate neurological disorders. Despite promising results, the current data underscore the challenges in future research on the therapeutic benefits of probiotics and postbiotics for neurological illnesses and underscores the critical role of the gut-brain connection and the microbiome in maintaining neurological health. It also examines the safety and feasibility of using probiotics and postbiotics as adjunct therapies, delving into the mechanisms underlying their beneficial effects. Probiotics and postbiotics demonstrate a capacity to enhance the regenerative potential of the human brain, and recent evaluations provide additional evidence supporting their efficacy and safety. However, further rigorous clinical trials are necessary to validate these findings and establish the most effective therapeutic strategies for treating neurological disorders.
INTRODUCTION: Background: Melanoma is considered the deadliest form of skin cancer. While monoclonal-antibodies and molecular targets marked milestones in melanoma therapy, more research is needed to overcome the advance...INTRODUCTION: Background: Melanoma is considered the deadliest form of skin cancer. While monoclonal-antibodies and molecular targets marked milestones in melanoma therapy, more research is needed to overcome the advanced stages of this disease. OBJECTIVE: To explore the possible use of the yeast cytosine deaminase::uracil phosphoribosyltransferase fusion enzyme/5-fluorocytosine (CD::UPRT/5FC) suicide gene (SG) system for human melanoma. METHODS: In eight metastatic human melanoma cell lines, we determined: cytotoxicity, lipofection efficiencies, colony forming capacity and bystander effects due to soluble and/or particulate factors secreted to the conditioned media after treatments. RESULTS: CD::UPRT induced cell death in a prodrug (5FC) concentration-dependent manner and was able to eliminate the sub-population of surviving cells with clonogenic capacity. Compared with human interferon-β gene transfer or the herpes simplex virus thymidine kinase/ganciclovir system, at 100 μM 5FC, CD::UPRT was more efficient in inducing cell death. The strong cytotoxic response contrasted with the low lipofection efficiencies (<5%), indicating a potent bystander effect. We analyzed the contribution of soluble and particulate factors released by SG lipofected cells to the conditioned media (CM) finding that they were able to deliver CD::UPRT genetic information and/or recombinant enzyme to recipient cells. When exposed to 5FC, the cells that received either supernatant or 12000×g pellet fractions of CM, efficiently activated the prodrug because of the acquired CD::UPRT activity and caused cell death. CONCLUSION: This suicide gene therapy approach, amplified by the release of free 5-fluorouracil and soluble and particulate factors containing CD::UPRT genetic information and/or enzyme, could have a great clinical potential for malignant melanoma.
Breast cancer remains a critical health concern, requiring continual innovation in treatment to improve patient outcomes. The continuous obstacles in therapy and the need for novel techniques underline the importance of...Breast cancer remains a critical health concern, requiring continual innovation in treatment to improve patient outcomes. The continuous obstacles in therapy and the need for novel techniques underline the importance of making advances in this discipline. Precision medicine has emerged as a viable method, with genomic profiling and molecular subtyping allowing for targeted therapy based on distinct breast cancer subtypes. This strategy is supplemented by advances in early detection and screening, with technologies like liquid biopsy promising earlier and more accurate diagnosis. The introduction of immunotherapy has transformed breast cancer treatment by using the body's immune system to combat cancer. Recent discoveries, particularly combination medicines, attempt to circumvent resistance mechanisms and improve treatment success. Furthermore, including lifestyle therapies such as nutrition, exercise, and psychological support has been demonstrated to reduce breast cancer risk and strengthen survivability rates. Survivorship programs serve an important role in comprehensive care by addressing long-term needs and enhancing survivors' quality of life. Investigating innovative therapeutic approaches, such as developing cancer vaccines, epigenetic modulators, and RNA interference (RNAi) therapy, provides new treatment options. Fostering collaboration among healthcare personnel through shared decision-making and tumor committees is essential for the integration of multidisciplinary care, which ensures patientcentered care. Although advancements have been made, there are still numerous obstacles to overcome in the implementation of these future directions. To effectively confront these obstacles, it is imperative to capitalize on opportunities for innovation and collaboration. It is imperative to address ethical, social, and economic factors in the advancement of breast cancer care to ensure that innovations are equitable and accessible. In conclusion, the future of breast cancer management is bright since substantial improvements are on the verge of turning patient treatment into a completely different experience. For these breakthroughs to become a reality, it is necessary to maintain research efforts, advocate for them, and work together. The dedication to innovation and the joint effort to overcome current problems are the two important factors that will determine whether or not breast cancer treatment and surviving will have a better future.
OBJECTIVE: The aim of this study was to elucidate the causal relationship between the consumption of processed and red meats (specifically pork, beef, and mutton) and susceptibility to various lung cancer types. BACKGROU...OBJECTIVE: The aim of this study was to elucidate the causal relationship between the consumption of processed and red meats (specifically pork, beef, and mutton) and susceptibility to various lung cancer types. BACKGROUND: Previous observational studies have indicated a potential cancer risk associated with red and processed meat consumption. However, a clear causal relationship remains undetermined. PURPOSE: Refining the study of the association between processed and red meat and lung cancer using a Mendelian randomization study. METHOD: We harnessed the robustness of Two-Sample Mendelian Randomization, integrating data from the esteemed UK Biobank, capturing dietary habits with oncological datasets from the Transdisciplinary Research In Cancer of the Lung. The analytical approach was anchored in the inverse variance weighted (IVW) method, enriched by sensitivity analyses for result validation. RESULT: Genetic predispositions favoring processed meat consumption are linked to heightened risks of lung cancer [IVW analysis, OR=1.8203, 95%CI [1.1115,2.9811], p=0.0173], and in LUSC [IVW analysis, OR=2.9274, 95%CI [1.4810,5.7863], p=0.0020]. Beef was more important in lung cancer [IVW analysis, OR=4.6739, 95% CI [2.4947, 8.7570], p=0.000001], in LUSC [IVW analysis, OR=3.3251, 95%CI [1.2055,9.1717], p=0.0203] and in LUAD [IVW analysis, OR=7.1480, 95%CI [3.0074,16.9893], p=0.000008]. However, no significant links were identified between mutton or pork intake and lung cancer. CONCLUSION: Processed meat and beef consumption may elevate lung cancer risk. Additional research is warranted to investigate potential links between mutton or pork consumption and the risk of lung cancer.
INTRODUCTION: Pain, infection, and dry socket are the primary complications following tooth extraction. Hence, the aim of this study was to evaluate the pain range and incidence of dry socket after using a hemostatic spo...INTRODUCTION: Pain, infection, and dry socket are the primary complications following tooth extraction. Hence, the aim of this study was to evaluate the pain range and incidence of dry socket after using a hemostatic spongy material containing aloe vera nanoparticles after split-mouth extraction of the mandibular first and second molars, compared to a control sponge without aloe vera nanoparticles in patients referred to the Tabriz Faculty of Dentistry. MATERIALS AND METHODS: This double-blind, split-mouth clinical study was conducted on 30 patients referred to the Faculty of Dentistry in Tabriz. Patients were selected according to specific inclusion and exclusion criteria and required extraction of two teeth. After tooth extraction, an aloe vera nanoparticle-containing hemostatic sponge was randomly placed in one extraction site, while a sponge without aloe vera nanoparticles served as the control in the other extraction site. Pain levels were measured at 12, 24, 48, and 72 h after extraction using a Visual Analog Scale (VAS), where patients marked their pain level from 1 (lowest pain) to 10 (highest pain) at each time point. Patients received a form to record the required information and instructions on how to do so, which they submitted upon completion. To assess the occurrence of dry socket, patients were asked to come four days after extraction. Data were analyzed using SPSS software with relevant statistical tests, considering a significance level of P<0.05. RESULTS: In both groups, the average pain levels decreased significantly over 72 h (P=0.001 and P=0.01 for the test and control groups, respectively). Additionally, for 48 h and 72 h time points, the test group showed better pain control results than the control group (P=0.04 and P=0.04 for 48 h and 72 h, respectively). No cases of dry sockets were found in either group. CONCLUSION: The aloe vera-containing sponge demonstrated better performance in pain control following tooth extraction compared to the control group. For dry socket occurrence, both sponges showed similar results.
COVID-19 is an ongoing pandemic caused by the SARS-CoV-2 coronavirus that is one of the most significant challenges to public health over the past few years. Most people are vulnerable to SARS-CoV-2, but older adults are...COVID-19 is an ongoing pandemic caused by the SARS-CoV-2 coronavirus that is one of the most significant challenges to public health over the past few years. Most people are vulnerable to SARS-CoV-2, but older adults are more vulnerable. Aging is one of the major risk factors for the detrimental consequences of COVID-19, likely due to chronic inflammation and immunosenescence, both of which are the characteristics of old age. Immunosenescence refers to the weakening of the immune system with age while inflammaging describes the low-grade chronic inflammation seen in older individuals. One key aspect of human aging is immune deficiency. During aging, our body's defense system weakens, resulting in decreased responses to infection by novel pathogens and a reduced ability to become immunized. The presence of chronic inflammation and viral infection in old age may cause several adverse unpredictable outcomes increasing the propensity and severity of the disease and requires to be considered, enabling people to better prepare for the potential consequences of this ongoing pandemic. This requires consideration so that individuals can better be prepared to address the potential consequences of this ongoing pandemic. In this review, we discuss the clinical characteristics of elderly COVID-19 patients and survey the associated molecular pathways that are pivotal for the interactions of the coronavirus and host cellular responses, including immunosenescence, inflammation, telomere attrition, impaired autophagy, mitochondrial dysfunction and alterations in major aging signaling pathways, which are crucial for the discovery of new therapeutic and preventive methods in the ongoing pandemic.
OBJECTIVES: Polygonati rhizoma (PR) has been used for thousands of years to alleviate dementia. Here, we aimed to elucidate the effect of alleviating vascular dementia (VaD) and underlying mechanism of PR. METHODS: In vi...OBJECTIVES: Polygonati rhizoma (PR) has been used for thousands of years to alleviate dementia. Here, we aimed to elucidate the effect of alleviating vascular dementia (VaD) and underlying mechanism of PR. METHODS: In vivo, rats were treated with two-vessel occlusion (2VO) induces VaD. The anti-VaD effect measured by learning and memory capacity, cerebral pathological structure, and cerebral microglial M1/M2 phenotype biomarkers. Subsequently, screening potential mechanisms of PR for VaD using network pharmacology and molecular docking methods. Moreover, the efficacy of PR-contained serum on LPS-induced inflammation and polarization on BV2 microglia was evaluated with NF-κB/NLRP3 pathway. RESULTS: In vivo, PR significantly enhanced learning and memory capacity, suppressed M1 microglia activation and promoted M2 polarization. Through network pharmacology and molecular docking approaches, we screened inflammation as a potential mechanism for PR anti-VaD, with targets involving NF-κB. Meanwhile, PR could regulate the expression of NF-κB/NLRP3 pathway compared with that of LPS-induced BV2 cells. Furthermore, by utilizing PDTC, an NF-κB antagonist, it was found that the effect of PR was similar to that of PDTC. CONCLUSION: PR could hamper inflammation and microglial polarization in 2VO-induced VaD and LPS-induced BV2 cells. Our results showed that PR was a promising Chinese herb to alleviate VaD, and the potential mechanism might be related to NF-κB/NLRP3 signaling pathway.
AIMS: The study aims to investigate the impact of curcumin on the structure of betaamyloid peptide dimers and how carbon nanotubes influence this interaction. The research focuses on understanding the molecular dynamics...AIMS: The study aims to investigate the impact of curcumin on the structure of betaamyloid peptide dimers and how carbon nanotubes influence this interaction. The research focuses on understanding the molecular dynamics and structural changes induced by curcumin to reduce beta-amyloid toxicity. Curcumin, a phenolic compound, is known for its ability to prevent the aggregation of beta-amyloid peptides, which are associated with neurodegenerative diseases. Despite its recognized inhibitory action on beta-amyloid aggregation, there is limited understanding of its precise effects on the peptide's structure. This study addresses this gap by employing molecular dynamics simulations and density functional theory methods. To elucidate the structural effects of curcumin on beta-amyloid peptide dimers and assess the modifying role of carbon nanotubes using computational methods. METHOD: The effect of curcumin on beta-amyloid peptide dimers was studied using molecular dynamics simulations and density functional theory. The simulations were conducted both in the presence and absence of carbon nanotubes to assess their influence on curcumin's activity and the structural stability of the peptide. RESULTS: The presence of curcumin and carbon nanotubes induced relative instability in betaamyloid dimers. Curcumin exhibited stronger interactions with the N-terminal and C-terminal regions of the peptide than with the middle section. It also reduced the toxicity of the peptide by particularly affecting the salt bridge and the arrangement of Phe19, Ile31, and Leu34 residues. Carbon nanotubes mitigated curcumin's effects on the peptide, altering curcumin's behavior by reducing its activity but increasing its solvation energy. CONCLUSION: Curcumin plays a significant role in destabilizing beta-amyloid dimers and reducing their toxicity, with its effect being modulated by the presence of carbon nanotubes. This dual influence highlights the potential of using curcumin, alongside nanomaterials, in therapeutic strategies for neurodegenerative diseases. Other: The study provides valuable insights into the molecular interactions between curcumin, beta-amyloid peptides, and carbon nanotubes. These findings can contribute to the development of more effective treatments targeting amyloid-related toxicity in neurodegenerative conditions.
OBJECTIVES: The aim of this study was to develop a clinical application model for the rational use of caffeine. BACKGROUND: Caffeine is related to the incidence of neuro immune gastrointestinal diseases. Coffee consumpti...OBJECTIVES: The aim of this study was to develop a clinical application model for the rational use of caffeine. BACKGROUND: Caffeine is related to the incidence of neuro immune gastrointestinal diseases. Coffee consumption needs to be optimized in order to reduce the incidence rate. PURPOSE: By using KEEG analysis to explore potential molecular signaling pathways involved in the progression of neurological immune gastrointestinal diseases, and analyzing the details of this signaling Pathway using molecular simulation results, which can support AI system for doctor. METHODS: The research team designed a controlled experiment to analyze the differences in reward and reinforcement of Brain pleasure/addiction and dopamine related signaling pathways function between multiple groups of people with different coffee drinking habits and a blank control group. The study team used molecular dynamics methods to investigate the signaling route that links coffee with the binding of dopamine receptor D3.AI is used to predict the prevalence of gastric reflux disease. RESULTS: Human experiments have shown a correlation between caffeine intake and gastroesophageal reflux disease. AI algorithm results can provide clinical support, and molecular simulation results are consistent with human experimental results. Caffeine and DRD3 protein have a stable interaction system. CONCLUSION: The research team elucidated the intermolecular interaction between caffeine and DRD3, and AI algorithms can predict the likelihood of disease occurrence, providing a new strategy for clinical practice. This study has passed ethical approval at Chifeng Cancer Hospital, and the ethical documents for this study have been submitted to the World Health Organization for filing.
BACKGROUND: Breast Cancer (BRCA) is one of the most common cancers worldwide. Abnormal Alternative Splicing (AS) is frequently observed in cancers. Understanding the intricate relationship between gene mutations and abno...BACKGROUND: Breast Cancer (BRCA) is one of the most common cancers worldwide. Abnormal Alternative Splicing (AS) is frequently observed in cancers. Understanding the intricate relationship between gene mutations and abnormal AS is vital for developing novel diagnostic and therapeutic strategies to effectively target cancer. OBJECTIVE: This study aimed to focus on the analysis of transcriptomic splicing events in patients with Breast Cancer (BRCA), particularly those with mutations in the TP53 gene. Understanding the role of AS may be helpful in revealing potential predictive indicators for survival and treatment strategies. METHODS: The splicing data were downloaded from the Cancer Genome Atlas (TCGA) breast cancer project, incorporating 972 patients in the study, classified according to TP53 mutation status. A comprehensive splicing profile of these breast tumors was outlined, and an interaction network of Alternative Splicing (AS) events and splicing factors was constructed. This allowed for the identification of specific AS events associated with TP53-mutant breast cancer. A prognostic risk model based on AS events was established, using univariate and multivariate Cox regression analyses. To understand the molecular heterogeneity, consensus clustering analyses of prognostic AS events were performed. We also investigated the association of AS patterns with the immune microenvironment and drug sensitivity. RESULTS: A total of 4519 significant Alternative Splicing (AS) events were distributed among 2729 genes that were altered in TP53 mutant tumors. Based on the analysis of these events, a prognostic risk model was created involving ten AS events from ten genes (such as NKTR, CD46, VCAN, etc.). The survival analysis showed that patients with high-risk scores had significantly poorer overall survival (p<0.001, HR=2.46, 95% CI 1.90-3.18) than those with low-risk scores. Furthermore, the study identified four molecular subtypes related to AS events (C1, C2, C3, and C4), which showed significant differences in immune cell infiltration, with C1 and C4 clusters having a higher degree of immune cell infiltration than C2 and C3. The chemosensitivity analysis revealed that these different AS clusters have different sensitivities to several anticancer drugs, such as docetaxel, paclitaxel, and doxorubicin, with C1 and C4 clusters being more sensitive than the other clusters. CONCLUSION: We have demonstrated differential transcriptomic splicing events between TP53 mutant and wild-type cases of breast cancer, establishing an effective prognostic risk model based on AS events. These findings provide new insights that may aid in understanding the biological behavior of breast cancer and potentially in optimizing treatment strategies for breast cancer.
BACKGROUND: Atherosclerosis (AS) is caused by the endothelium injury associated with oxidative stress. Previous studies have shown that the Phlegm-Eliminating and Stasis- Transforming Decoction (Huayu Qutan Decoction, HY...BACKGROUND: Atherosclerosis (AS) is caused by the endothelium injury associated with oxidative stress. Previous studies have shown that the Phlegm-Eliminating and Stasis- Transforming Decoction (Huayu Qutan Decoction, HYQTD) has mitochondrial protective function. The objective of this research was to explore how HYQTD drug-containing serum (HYQTD-DS) could potentially protect mitochondrial energy production in endothelial cells (ECs) from injury caused by hydrogen peroxide (HO)-induced oxidative damage in AS through SIRT1/PGC-1α/ Nrf2 pathway. METHODS: After preparation of containing serum, the cells were divided into various categories, such as control group, HO group (an oxidative damage model), HYQTD group, Selisistat (EX527, a SIRT1 inhibitor) combined with HO group, and EX527 combined with HYQTD group. The evaluation of oxidative stress involved measuring reactive oxygen species (ROS) and malondialdehyde (MDA) generation, as well as Superoxide Dismutase (SOD) activity. Mitochondrial function and ultrastructure were measured by Transmission electron microscopy (TEM), mitochondrial membrane potential (MMP), rate of oxygen consumption (OCR), respiratory chain complex activities and ATP production. The key proteins and gene levels in the SIRT1/PGC-1α/Nrf2 pathway was quantified by quantitative real-time PCR (RT-PCR) and Western blotting analysis. RESULTS: We found oxidative stress, mitochondrial damage, and mitochondrial energy disorder in HO-induced ECs. However it indicated a marked reversal after pretreated with HYQTD-DS. Mechanistically, EX527 induced increased oxidative stress, worse mitochondrial dysfunction, and less ATP synthesis. CONCLUSION: We demonstrated that HYQTD-DS attenuated oxidative stress, improved mitochondrial function, and up-regulated mitochondrial ATP synthesis by activating SIRT1/PGC- 1α/Nrf2 pathway-induced mitochondrial biogenesis and its downstream NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDV2).
According to epidemiological studies, diabetes is more common in patients with AD, which suggests that diabetes is a significant risk factor for AD. Accelerating brain cell degeneration, worsening cognitive decline, and...According to epidemiological studies, diabetes is more common in patients with AD, which suggests that diabetes is a significant risk factor for AD. Accelerating brain cell degeneration, worsening cognitive decline, and increasing susceptibility to AD can be attributed to pathogenic mechanisms linked to diabetes, such as impaired insulin signaling in the brain, neuroinflammation, oxidative stress, mitochondrial dysfunction, and vascular impairment. These factors can also lead to the accumulation of β-amyloid and tau protein phosphorylation. New research suggests that certain drugs used to manage diabetes have different levels of effectiveness in treating or preventing Alzheimer's disease. Exercise has numerous advantages, including the reduction of neuroinflammation, alleviation of oxidative stress and mitochondrial dysfunction, improvement of endothelial and cerebrovascular function, stimulation of neurogenesis, and prevention of pathological changes associated with diabetes-related Alzheimer's disease through various internal mechanisms. This study examined the development of Alzheimer's disease (AD) in relation to diabetes, evaluated the ability of specific antidiabetic drugs to prevent and treat AD, and investigated the impacts and underlying processes of exercise interventions in improving AD treatment for individuals with diabetes.
BACKGROUND: Gene therapy has been effectively applied in many biological studies and for the treatment of many genetic or cancer diseases. Currently, Recombinant Adeno- Associated Viruses (rAAVs) are one of the main type...BACKGROUND: Gene therapy has been effectively applied in many biological studies and for the treatment of many genetic or cancer diseases. Currently, Recombinant Adeno- Associated Viruses (rAAVs) are one of the main types of delivery vectors used for gene therapy. rAAV vectors produced via the Sf9 cells have the advantages of high rAAV yields, easy scaleup, and low cost. METHOD: Here, we used Sf9 rhabdovirus-negative (Sf9-RVN) cells to validate and optimize the rAAV production process, and the fed-batch process increased the rAAV production titre. RESULTS: In the fed-batch procedure, the cell density reached 12.9×106 cells/mL, which was approximately twice as high as in the batch culture process. The rAAV titre was also approximately 8-fold higher in the fed-batch process, reaching 1.5×10 VG/mL. The optimized process was validated by generating rAAVs with various serotypes and genes of interest (GOI), all of which gave production titres greater than 1×10 VG/mL. CONCLUSION: We used Sf9-RVN cells to develop a fed-batch rAAV production process that replaces Sf9 cells to meet regulatory standards. This process has good applicability, and the rAAV titre can reach at least 1×10 VG/mL, which is higher than the level of 10 VG/mL reported in the literature.
Artificial intelligence (AI) is a rapidly transforming drug discovery and development process, significantly impacting the pharmaceutical industry and enhancing human health. This review article examines the tremendous r...Artificial intelligence (AI) is a rapidly transforming drug discovery and development process, significantly impacting the pharmaceutical industry and enhancing human health. This review article examines the tremendous role of AI in analyzing complex biological data, optimizing research processes, and reducing costs of production. Implementation of AI in the pharmaceutical sector can store a vast dataset of manufacturing processes, identify potential disease targets, simulate physiological conditions, and predict drug interactions. The review article also discusses the AI concepts and their applications, particularly in developing solid dosage forms. Advanced algorithms optimize formulation processes, predict pharmacokinetics profiles, and assess drug toxicity profiles, facilitating a more efficient pathway from pilot study to market. Additionally, this review highlights the advancements in 3D printing technologies of dosage forms that have the ability to provide personalized treatment to different individuals. Furthermore, the article explores the opportunities and challenges of AI in healthcare, focusing on applications such as disease diagnosis, digital therapy, and epidemic forecasting. Prominent AI technologies like deep learning and neural networks are examined for their roles in predicting outbreaks of diseases like influenza and COVID-19. As the pharmaceutical landscape evolves, AI is poised to redefine traditional methods. This paves the way for more efficient healthcare solutions. By harnessing the interplay of technology and science, AI not only increases productivity; but it also promotes a new era of precision medicine tailored to the needs of each patient.
OBJECTIVE: This study evaluated the renoprotective effects of p-Coumaric acid nanoparticles (PCNPs) in nephropathic rats. METHODS: Six groups of male Albino Wistar rats were randomly assigned. Group 1 was the control, wh...OBJECTIVE: This study evaluated the renoprotective effects of p-Coumaric acid nanoparticles (PCNPs) in nephropathic rats. METHODS: Six groups of male Albino Wistar rats were randomly assigned. Group 1 was the control, while Group 2 received 45 mg/kg of streptozotocin (STZ) to induce diabetic nephropathy. Groups 3, 4, and 5 received STZ (45 mg/kg) along with PCNPs at doses of 20, 40, and 80 mg/kg, respectively. Group 6 received 80 mg/kg of PCNPs without STZ. Body weight, blood glucose, insulin, hemoglobin (Hb), and glycosylated hemoglobin (HbA1c) levels were measured. Blood urea, serum creatinine, kidney antioxidant enzymes, and lipid peroxidation levels were also analyzed. Histological and immunohistochemical studies of kidney tissues were performed. RESULTS: PCNPs (80 mg/kg) significantly reduced serum glucose, creatinine, and urea levels while increasing insulin levels and antioxidant activity in the kidneys. Histological analysis revealed that nephropathic rats exhibited cellular damage, including shrinkage of Bowman's capsule and lesions in the kidneys, along with degeneration in the Islets of Langerhans in the pancreas. PCNPs treatment restored these morphological alterations in the pancreas, liver, and kidneys to near-normal. Furthermore, nephropathic rats had elevated IL-6 and TNF-α expression in the renal tubules and glomeruli, which was reduced following PCNPs treatment. CONCLUSION: The findings suggest that PCNPs exhibit antihyperglycemic, antioxidant, antiglycation, and renoprotective effects in STZ-induced diabetic nephropathy.
The emergence of multiple antibiotic resistance in recurrent bacterial infections has led to exploring alternative therapeutic options, including using bacteria lysing viruses [bacteriophages] to control recalcitrant inf...The emergence of multiple antibiotic resistance in recurrent bacterial infections has led to exploring alternative therapeutic options, including using bacteria lysing viruses [bacteriophages] to control recalcitrant infections. Bacteriophages [Phage] and their end products such as enzymes, virus-like particles, and vectors are being used for varied applications such as basic and applied research for the field of phage therapeutics. Phage-based products and services such as viral vectors for gene therapy/vaccines, imaging agents, diagnostics as well as drug delivery agents form a wide range of useful innovative therapeutics that are under development. Regulatory compliances are hence essential for safely implementing phage in varied applications. Product compliances ensure safety, efficacy, stability, and quality control in preclinical as well as manufacturing and marketing processes. A well-established regulatory framework ensures innovative product development with high rates of successful clinical translation and development of phage therapeutics as effective alternatives to antibiotics or for consideration in integrated pathogen management strategies. This review highlights the importance of regulatory standards in different stages of phage therapy- during preclinical research as well as different regulatory bodies in the manufacturing, clinical evaluation, and market approval of phage-based products. Global trends in facilitating phage therapeutics' regulatory frameworks and compliances are discussed.