Effectiveness Of Drugs Research Articles

Investigation of Advanced Nanoscale Biomaterials as Immune Modulators for Therapeutic Applications

Immunomodulatory agents play a crucial role in drug delivery by modulating the immune system's response to therapeutic agents, thereby enhancing treatment efficacy and safety. These agents can either stimulate the immune system to improve drug effectiveness, particularly in cancer and infectious diseases, or suppress it to prevent adverse reactions in conditions like organ transplantation and autoimmune diseases. The integration of immunomodulatory agents into drug delivery systems (DDS) enhances drug targeting, controls release, and optimizes pharmacokinetics. Advanced carriers such as nanoparticles and liposomes are employed to precisely deliver these agents, aligning with personalized medicine approaches to tailor treatments based on individual immune profiles. Despite their potential, challenges such as balancing immune modulation and addressing safety concerns remain. Ongoing research is focused on developing innovative DDS, improving targeting strategies, and identifying new immunomodulatory compounds to address these challenges. This abstract provides an overview of the role and impact of immunomodulatory agents in drug delivery systems and highlights the current trends and future directions in this evolving field.

SCGB1A1 as a novel biomarker and promising therapeutic target for the management of HNSCC.

Head and neck cancer (HNC) is the sixth most common type of cancer worldwide, and head and neck squamous cell carcinoma (HNSCC) accounts for 90% of HNC cases. Furthermore, HNSCC accounts for 400,000 cancer-associated deaths worldwide each year. However, at present there is an absence of a versatile biomarker that can be used for diagnosis, prognosis evaluation and as a therapeutic target for HNSCC. In the present study, bioinformatics analysis was used to assess the relationship between hub genes and the clinical features of patients with HNSCC. The findings from the bioinformatics analysis were then verified using clinical samples and in vitro experiments. A total of 51 overlapping genes were identified from the intersection of differentially expressed genes and co-expressed genes. The top 10 hub genes were obtained from a protein-protein interaction network of overlapping genes. Among the hub genes, only secretoglobin family 1A member 1 (SCGB1A1) was significantly associated with both overall and disease-free survival. Specifically, upregulated SCGB1A1 expression levels were associated with prolonged overall and disease-free survival. Moreover, the SCGB1A1 expression levels were negatively correlated with drug sensitivity. Notably, it was demonstrated that SCGB1A1 was involved in tumor immunoreaction by affecting the infiltration of cells and checkpoint regulation of immune cells. Additionally, it was shown that SCGB1A1 regulated multiple key cancer-related signaling pathways, including extracellular matrix receptor interaction, transforming growth factor-β and tumor metabolism signaling pathways. Based on the results of the present study, SCGB1A1 may serve as a novel biomarker for predicting the diagnosis, prognosis and therapeutic effectiveness of certain drugs in patients with HNSCC. Moreover, SCGB1A1 may serve as a potential therapeutic target for the management of HNSCC.

Probiotaceuticals: Back to the future?

Probiotic research has undergone some exciting and unanticipated changes in direction since the 2010 commentary by GSH, which speculated on probiotics being ultimately utilized as “factories” capable of releasing pharmaceutical-grade metabolites with therapeutic potential for a wide range of primarily gastrointestinal disorders. Indeed, the unrelenting search for new alternatives to antibiotics has further stimulated the development of “next-generation” probiotics. Postbiotics, defined as inanimate microorganisms and/or their components that confer a health benefit on the host, remain at the forefront of current probiotic research, with increasing numbers of probiotic species, strains, and substrains now being identified and further exploited as pharmabiotics; probiotics with a proven pharmacologic role in health and disease that have been subjected to clinical trial prior to approval by regulatory bodies. However, perhaps the most unanticipated probiotic development over the past 15 y has been the emergence of psychobiotics with the potential to improve aspects of mental health, such as depression and anxiety, through the release of bioactive metabolites. Moreover, the recent identification of pharmacobiotics, probiotics capable of facilitating the effectiveness of conventional pharmaceutical drugs, is opening new avenues for probiotic applications to combat a range of diseases, including cancers of the digestive system. Although in its infancy, recent reports of oncobiotics with antineoplastic properties are further expanding the potential for certain next-generation probiotics to impact current cancer treatment regimens and possibly even contribute to cancer prevention. Looking to the next 15 y of probiotic development, one could perhaps predict the ultimate development of regulatory-approved xenopostbiotic formulations comprising metabolites with the capacity to improve digestive health, decrease the severity of intestinal disease, and increase the effectiveness of conventional pharmaceuticals, whilst simultaneously improving cognitive functioning and mental welfare. Although speculative, these xenopostbiotic formulations could prove especially effective for the adjunctive treatment of serious chronic diseases such as cancer.

51352 Drug survival, effectiveness, and safety of brodalumab for moderate-to-severe psoriasis up to 3 years

51352 Drug survival, effectiveness, and safety of brodalumab for moderate-to-severe psoriasis up to 3 years

In Silico and Glioblastoma Cell Line Evaluation of Thioflavin-Derived Zinc Nanoparticles Targeting Beclin Protein.

This study explores the anticancer potential of Thioflavin-derived zinc nanoparticles (Th-ZnNPs) using both in vitro and in silico methods. Thioflavin, known for its specific binding properties, faces challenges such as bioavailability, rapid metabolism, and solubility. To overcome these limitations and enhance therapeutic efficacy, nanotechnology was utilized to synthesizeTh-ZnNPs. These nanoparticles (NPs) are designed to improve drug delivery and effectiveness. The Beclin protein, which plays a critical role in regulating autophagy in cancer cells, was identified as a potential target for these NPs. The study aims to evaluate the interaction between Th-ZnNPs and Beclin protein in glioblastoma cell lines and assess the potential of these NPs as novel anticancer agents. Th-ZnNPs were synthesized using advanced nanotechnology techniques to improve the bioavailability and solubility of Thioflavin. To explore their anticancer potential, in silico analyses were performed, including molecular docking studies to evaluate the binding affinity between the ZnNPs and Beclin protein, which is integral to autophagy regulation. This computational approach identified the Beclin protein as a promising target for the ZnNPs. Complementary in vitro assays were then conducted, where glioblastoma cell lines (procured from the National Centre for Cell Science, Pune, India) were treated with ZnNPs to assess their cytotoxic effects. The assays also included mechanistic studies to validate the interaction between ZnNPs and Beclin protein and to understand their influence on autophagy pathways. The synthesis ofTh-ZnNPs successfully enhanced their solubility and bioavailability compared to Thioflavin alone. In silico findings showed a strong binding affinity between the Th-ZnNPs and the Beclin protein, suggesting that these NPs may effectively target cancer cells through this interaction. Beclin protein was validated as a relevant target due to its critical role in autophagy regulation. In vitro assays further confirmed the anticancer potential of the Th-ZnNPs, as they exhibited significant cytotoxic effects on glioblastoma cells. Additionally, mechanistic studies revealed that Th-ZnNPs impact Beclin protein and modulate autophagy pathways, supporting their proposed role as effective anticancer agents. The study highlights the promising anticancer potential of Th-ZnNPs. By overcoming the limitations of Thioflavin through nanotechnology, these NPs show significant therapeutic promise in targeting glioblastoma cells. The strong binding affinity between Th-ZnNPs and the Beclin protein, coupled with confirmed cytotoxiceffects, underscores their potential as novel anticancer agents. This integrated approach not only enhances the delivery and efficacy of Thioflavin but also opens new avenues for targeted therapy in glioblastoma treatment.

A new perspective on antiangiogenic antibody drug resistance: Biomarkers, mechanisms, and strategies in malignancies.

Drug resistance of malignant tumor leads to disease progression be the bottleneck in clinical treatment. Antiangiogenic therapy, which aims to "starve" the tumor by inhibiting angiogenesis, is one of the key strategies in clinical oncology treatments. Recently, dozens of investigational antibody drugs and biosimilars targeting angiogenesis have obtained regulatory approval for the treatment of various malignancies. Moreover, a new generation of bispecific antibodies based on the principle of antiangiogenesis are being advanced for clinical trial to overcome antiangiogenic resistance in tumor treatment or enhance the efficacy of monotherapy. Tumors often develop resistance to antiangiogenesis therapy, presenting as refractory and sometimes even resistant to new therapies, for which there are currently no effective management strategies. Thus, a detailed understanding of the mechanisms mediating resistance to antiangiogenesis antibodies is crucial for improving drug effectiveness and achieving a durable response to antiangiogenic therapy. In this review, we provide a novel perspective on the tumor microenvironment, including antibody structure, tumor stroma, and changes within tumor cells, to analyze the multifactorial reasons underlying resistance to antiangiogenesis antibodies. The review also enumerates biomarkers that indicate resistance and potential strategies for monitoring resistance. Furthermore, based on recent clinical and preclinical studies, we summarize potential strategies and translational clinical trials aimed at overcoming resistance to antiangiogenesis antibodies. This review provides a valuable reference for researchers and clinical practitioners involved in the development of new drugs or therapeutic strategies to overcome antiangiogenesis antibodies resistance.

The effect of liposomal composition with encapsulated potassium orotate on the macrophage link of immunity in the treatment of wounds

In veterinary medicine, treatment of wounds is one of the most important areas. A possible way to solve the problem of wound treatment is to activate the body's own protective reserves, primarily the immune system. Various immunostimulants and immunomodulators are widely used to activate the immune system. Known immunostimulants are derivatives of pyrimidine bases, in particular, potassium orotate (potassium salt of orotic acid). Orotic acid is found in milk and colostrum of animals. The use of orotic acid or its salts as immunostimulants is difficult due to their low bioavailability determined by their solubility in water. It is possible to increase the effectiveness of immunostimulators based on potassium orotate by including it in liposomes. Liposomes with encapsulated potassium orotate were obtained by shaking. The aim of the research was to study the activation of immunity macrophage link by liposomes with encapsulated potassium orotate. Evaluation of the effectiveness of the liposomal drug was carried out on rat wound models and on post-castration wounds of suckling pigs. Animal experiments were conducted according to bioethical norms. Complete wound healing in rats with the use of liposomal gel occurred on day 2, earlier than in the control with the use of Monclavit-1, while in the experimental group, compared with the control group, the content of leukocytes, lymphocytes, monocytes, platelets and granulocytes was significantly higher. The healing of surgical wounds in piglets after castration with the use of liposomal gel occurred 2 days earlier than with the use of the drug "Monclavit-1". There were no complications in both groups. Based on the analysis of literature data and the results of our own research, a scheme of the mechanism of action of a liposomal drug was proposed. The hypothesis about the mechanism of influence of liposomal composition on the macrophage link of immunity has been presented.

Investigation of Cytotoxicity and Lipid-lowering Effects of Rivea hypocrateriformis Desr. Leaf Extracts on HepG2 Cells: An In Vitro Study

Background and Purpose Chronic diseases, such as cardiovascular disease as well as type 2 diabetes, are associated with hyperlipidemia, characterized by high blood lipid levels. HepG2 cells, a human liver cancer cell line, have become a popular model for evaluating the effectiveness of drugs in treating hyperlipidemia. These cells are preferred due to their ability to mimic liver cell physiology and easy maintenance in culture. Methods In this study, HEP, HEC, HEA, and HEE extracts of Rivea hypocrateriformis were tested on HepG2 cells for cytotoxicity using the MTT assay. The IC50 values of the extracts were determined and compared to analyze their toxicity. Microscopic images of the cell lines were also examined to observe any structural changes induced by the extracts. Results and Conclusion The results showed that both HEC and HEE extracts exhibited significant toxicity on HepG2 cells at the highest concentration of 500 µg/ml. Gradual decreases in concentration led to a gradual rise in % cell viability. The IC50 values of HEC and HEE were calculated to be 61.49 µg/ml and 87.08 µg/ml, respectively, indicating that HEC was slightly more toxic than HEE. According to the results obtained using the vanilla method, HEC and HEE extracts markedly reduced lipid content compared to the oleic acid-induced group. The gene expression regulation of AMPK, FAS, LDL receptor, and HMG-CoA was investigated using the RT-PCR method. The results showed that the extract-treated groups exhibited higher AMPK and LDL receptor gene expression. In contrast, the HEE extract showed higher activity than HEC in suppressing the FAS gene. Overall, the findings suggest that HEC and HEE extracts have potential as anticancer and lipid-lowering agents. Detailed research is needed to understand how the active constituents work.

Comprehensive analysis of 2097 patients with dystrophinopathy based on a database from 2011 to 2021

BackgroundAn increasing number of clinical trials for new therapeutic strategies are underway or being considered for dystrophinopathy. Having detailed data on the natural progression of this condition is crucial for assessing the effectiveness of new drugs. However, there’s a lack of data regarding the long-term data on the natural course and how it’s managed in China. In this study, we offer a comprehensive overview of clinical and molecular findings, as well as treatment outcomes in the Chinese population.MethodsInstitutional data on all patients with dystrophinopathy from August 2011 to August 2021 were retrospectively reviewed. The data included geographic distribution, age at diagnosis, molecular findings, and treatment options, such as corticosteroids, cardiac interventions, and clinical outcomes.ResultsIn total, 2097 patients with dystrophinopathy, including 1703 cases of Duchenne muscular dystrophy (DMD), 311 cases of Becker muscular dystrophy (BMD), 46 cases of intermediate muscular dystrophy (IMD), and 37 cases categorized as “pending” (individuals with an undetermined phenotype), were registered in the Children’s Hospital of Fudan University database for dystrophinopathy from August 2011 to August 2021. The spectrum of identified variants included exonic deletions (66.6%), exonic duplications (10.7%), nonsense variants (10.3%), splice-site variants (4.5%), small deletions (3.5%), small insertions/duplications (1.8%), and missense variants (0.9%). Four deep intronic variants and two inversion variants were identified. Regarding treatment, glucocorticoids were administered to 54.4% of DMD patients and 39.1% of IMD patients. The median age at loss of ambulation was 2.5 years later in DMD patients who received glucocorticoid treatment. Overall, one cardiac medicine at least was prescribed to 7.4% of DMD patients, 8.3% of IMD patients, and 2.6% of BMD patients. Additionally, ventilator support was required by four DMD patients. Eligibility for exon skipping therapy was found in 55.3% of DMD patients, with 12.9%, 10%, and 9.6% of these patients being eligible for skipping exons 51, 53, and 45, respectively.ConclusionsThis is one of the largest studies to have evaluated the natural history of dystrophinopathy in China, which is particularly conducive to the recruitment of eligible patients for clinical trials and the provision of real-world data to support drug development.

Mechanisms of Luteolin Against Gastro-Esophageal Reflux Disease Based on Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

Luteolin is a naturally occurring flavonoid. The effectiveness of luteolin-rich drugs in treating gastro-esophageal reflux disease (GERD) through traditional Chinese medicine has been demonstrated. This study aimed to identify the potential targets and mechanisms of action of luteolin for the treatment of GERD. An innovative approach combining network pharmacology and molecular dynamics was used to explore the potential therapeutic mechanisms of luteolin and to facilitate the further development of GERD treatment. Drug and disease target information was screened from public databases to obtain 159 intersecting targets through the construction of Venn diagrams. Subsequently, a protein‒protein interaction (PPI) network was constructed, and 10 core targets were identified. Through Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, relevant biological processes, cellular components, and molecular functions related to the treatment of GERD were identified and revealed. KEGG pathway analyses showed enrichment of signaling pathways, including the TNF, IL-17, NF-kappa B, and Toll-like receptor pathways. The molecular docking results indicated that luteolin can effectively bind to 10 core targets. Finally, molecular dynamics simulations confirmed the formation of stable protein‒ligand complexes when IL6 binds to luteolin. In conclusion, network pharmacology, molecular docking, and molecular dynamics simulations were utilized to investigate the mechanism by which luteolin treats GERD. These findings establish a theoretical foundation for future research on the efficacy of luteolin in treating GERD.

Biopharmaceutical studies of a novel sedative sublingual lozenge based on glycine and tryptophan: A rationale for mucoadhesive agent selection

Effective sedative drugs are in great demand due to increasing incidence of nervous disorders. The present work was aimed to develop a novel sublingual sedative drug based on glycine and L-tryptophan amino acids. Carbopol and different hydroxypropyl methylcellulose species were alternatively tested as mucoadhesive agents intended to prolong tryptophan sublingual release time. A model lipid medium of fully hydrated L-α-dimyristoylphosphatidylcholine was used for optimal mucoadhesive agents selection. Simultaneous processes of drug release and diffusion in lipid medium were first investigated involving both experimental and theoretical approaches. Individual substances, their selected combinations as well as different drug formulations were consecutively examined. Application of kinetic differential scanning calorimetry method allowed us to reveal a number of specific drug-excipient effects. Lactose was found to essentially facilitate tryptophan release and provide its ability to get into the bloodstream simultaneously with glycine, which is necessary to achieve glycine-tryptophan synergism. Introduction of a mucoadhesive agent into the formulation was shown to change kinetics of drug-membrane interactions variously depending on viscosity grade. Among the mucoadhesive agents, hydroxypropyl methylcellulose species K4M and E4M were shown to further accelerate drug release, therefore they were selected as optimal. Thus, effectiveness of the novel sedative drug was provided by including some excipients, such as lactose and the selected mucoadhesive agent species. A dynamic mathematical model was developed properly describing release and diffusion in lipid medium of various drug substances. Our study clearly showed applicability of a lipid medium to meet challenges such as drug-excipient interactions and optimization of drug formulations.

The potential of lenvatinib in breast cancer therapy.

Breast cancer, as a highly prevalent cancer among women, is one of the main causes of female mortality due to cancer. There is a need for more treatment options to improve the survival time of breast cancer patients. Metastasis to distant organs is a standard indicator of advanced breast cancer and a primary cause of breast cancer mortality, making the control of breast cancer metastasis crucial. Targeted therapy, with its advantages of precision, high effectiveness, and minimal side effects, has garnered significant attention as a hot research topic in breast cancer treatment. Among these therapies, anti-angiogenic therapy aim to inhibit tumor angiogenesis, control tumor growth, and reduce metastasis. Additionally, anti-angiogenic therapy can restructure the tumor vasculature, enhancing the effectiveness of other anti-cancer drugs. Lenvatinib, an orally available small molecule multi-targeted tyrosine kinase inhibitor, exerts its anti-tumor effects mainly by inhibiting tumor angiogenesis and tumor cell proliferation. It has been approved for the treatment of thyroid cancer, renal cell carcinoma, and hepatocellular carcinoma. Due to its multi-targeted nature, lenvatinib not only has direct anti-tumor effects but also possesses immunomodulatory activity, which can enhance the tumor immune response. This makes it a promising candidate for a broad range of cancers. Recent studies have explored the role of lenvatinib in breast cancer, including its various mechanisms of action and its use as a monotherapy or in combination to control breast cancer progression. This review will summarize the molecular mechanisms and research progress of lenvatinib in breast cancer treatment, discussing its potential applications and therapeutic prospects in managing breast cancer.

The Role of Titanium Dioxide Nanoparticles on the Effectiveness of Erythropoietin Alfa Drug in Rats with Anemia Accompanied with Chronic Kidney Disease

The Role of Titanium Dioxide Nanoparticles on the Effectiveness of Erythropoietin Alfa Drug in Rats with Anemia Accompanied with Chronic Kidney Disease

Effect of a polyherbal Unani formulation on left ventricular diastolic dysfunction in hypertensive patients- a randomized single blind placebo controlled clinical trial.

Diastolic dysfunction represents an important pathophysiological intermediate between hypertension and heart failure. In the last two decades, the prevalence of heart failure patients having normal or near normal ejection fraction (EF) has increased to around 60 %. It thus poses a great morbidity and mortality risk to the population. In view of present scenario of high prevalence, lack of evidence-based therapy, and limited clinical trials, this study aimed to evaluate how a Unani formulation affects the improvement of the left ventricular diastolic function. This clinical trial was set up as a randomized, placebo-controlled study involving 35 participants, with 18 individuals in the test group and 17 in the control group. Test group received 3.5 g of a polyherbal Unani formulation in capsule form along with 35 mL of an extract of Borago officinalis L. (Arq-e-Gaozaban), divided into two doses after meals. Meanwhile, the control group received a placebo in the same manner over an eight-week period. Follow-ups were conducted every 15days to assess both subjective and objective parameters in all participants. The test formulation shows significant improvement in dyspnea and diastolic function from baseline to the end of trial (p<0.05), slight improvement in palpitations (p>0.05) and highly significant improvement in easy fatigability (p=0.001) as compared to the control. The present study shows the effectiveness of the test drug in enhancing the diastolic function of left ventricle and alleviating other symptoms associated with ventricular diastolic dysfunction. Nevertheless, additional research with longer follow-up durations is necessary to clarify its efficacy and establish optimal treatment approaches for ventricular diastolic dysfunction in Unani medicine.

Nanoparticle-Based Drug Delivery Systems in Inhaled Therapy: Improving Respiratory Medicine.

Inhaled nanoparticle (NP) therapy poses intricate challenges in clinical and pharmacodynamic realms. Recent strides have revolutionized NP technology by enabling the incorporation of diverse molecules, thus circumventing systemic clearance mechanisms and enhancing drug effectiveness while mitigating systemic side effects. Despite the established success of systemic NP delivery in oncology and other disciplines, the exploration of inhaled NP therapies remains relatively nascent. NPs loaded with bronchodilators or anti-inflammatory agents exhibit promising potential for precise distribution throughout the bronchial tree, offering targeted treatment for respiratory diseases. This article conducts a comprehensive review of NP applications in respiratory medicine, highlighting their merits, ranging from heightened stability to exacting lung-specific delivery. It also explores cutting-edge technologies optimizing NP-loaded aerosol systems, complemented by insights gleaned from clinical trials. Furthermore, the review examines the current challenges and future prospects in NP-based therapies. By synthesizing current data and perspectives, the article underscores the transformative promise of NP-mediated drug delivery in addressing chronic conditions such as chronic obstructive pulmonary disease, a pressing global health concern ranked third in mortality rates. This overview illuminates the evolving landscape of NP inhalation therapies, presenting optimistic avenues for advancing respiratory medicine and improving patient outcomes.

Safety and Effectiveness of Thiopurines and Small Molecules in Elderly Patients with Inflammatory Bowel Diseases.

The management of inflammatory bowel diseases (IBD) requires weighing an individual patient's therapeutic benefits and therapy-related complication risks. The immunomodulators that have been commonly used so far in IBD therapy are thiopurines, including 6-mercaptopurine and azathioprine. As our understanding of the IBD pathomechanisms is widening, new therapeutic approaches are being introduced, including the Janus kinase (JAK) inhibitors and Sphingosine 1-phosphate receptor (S1PR) modulators' development. Non-selective JAK inhibitors are represented by tofacitinib, while selective JAK inhibitors comprise filgotinib and upadacitinib. As for the S1PR modulators, ozanimod and etrasimod are approved for UC therapy. The number of elderly patients with IBD is growing; therefore, this review aimed to evaluate the effectiveness and safety of the oral immunomodulators among the subjects aged ≥60. Possible complications limit the use of thiopurines in senior patients. Likewise, the promising effectiveness of new drugs in IBD therapy in those with additional risk factors might be confined by the risk of serious adverse events. However, the data regarding this issue are limited.

Revisiting diabetes risk of olanzapine versus aripiprazole in serious mental illness care.

Exposure to second-generation antipsychotics (SGAs) carries a risk of type 2 diabetes, but questions remain about the diabetogenic effects of SGAs. To assess the diabetes risk associated with two frequently used SGAs. This was a retrospective cohort study of adults with schizophrenia, bipolar I disorder or severe major depressive disorder (MDD) exposed during 2008-2013 to continuous monotherapy with aripiprazole or olanzapine for up to 24 months, with no pre-period exposure to other antipsychotics. Newly diagnosed type 2 diabetes was quantified with targeted minimum loss-based estimation; risk was summarised as the restricted mean survival time (RMST), the average number of diabetes-free months. Sensitivity analyses were used to evaluate potential confounding by indication. Aripiprazole-treated patients had fewer diabetes-free months compared with olanzapine-treated patients. RMSTs were longer in olanzapine-treated patients, by 0.25 months [95% CI: 0.14, 0.36], 0.16 months [0.02, 0.31] and 0.22 months [0.01, 0.44] among patients with schizophrenia, bipolar I disorder and severe MDD, respectively. Although some sensitivity analyses suggest a risk of unobserved confounding, E-values indicate that this risk is not severe. Using robust methods and accounting for exposure duration effects, we found a slightly higher risk of type 2 diabetes associated with aripiprazole compared with olanzapine monotherapy regardless of diagnosis. If this result was subject to unmeasured selection despite our methods, it would suggest clinician success in identifying olanzapine candidates with low diabetes risk. Confirmatory research is needed, but this insight suggests a potentially larger role for olanzapine in the treatment of well-selected patients, particularly for those with schizophrenia, given the drug's effectiveness advantage among them.

Enhancing cancer immunotherapy and antiangiogenic therapy by regulating gut microbes: Opportunities and challenges

AbstractAs the largest microecosystem in the human body, gut microbes (GMs) and their metabolites play an important role in regulating human health. In recent years, immune checkpoint therapy (ICT) combined with antiangiogenic agents is an emerging combination therapy for cancer. There is growing evidence that GMs can affect the effectiveness of drugs to treat cancer. GMs not only regulate angiogenesis in the tumor microenvironment, but also influence the efficacy of immune checkpoint inhibitors. Many studies show that Bifidobacterium can upregulate the anticancer function of immune checkpoint blockers. In addition, GMs have been found to be involved in the formation of blood vessels and other developmental processes. Clinically, GMs are believed to play a key role in patients receiving antiangiogenic therapy and ICT. In this perspective, we provide an overview of the composition and function of the gut microbiome, and discuss the role of the GMs against the conditioning of angiogenic therapy and ICT. We also summarize new approaches and clinical translational trials using GMs for cancer therapy, and present opportunities and challenges for targeting GMs for cancer therapy in the future.

Prescription of non-steroidal anti-inflammatory and antirheumatic drugs in outpatient hypertensive patients.

It has been documented that NSAIDs (nonsteroidal anti-inflammatory and antirheumatic drugs) reduce the effectiveness of some antihypertensive drugs. Analyze the prescription of NSAID and the variables associated in outpatients with hypertension and explore some characteristics of the physicians. Cross-sectional study, included patients with hypertension from the Family Medicine Unit No. 24 in Mante, Tamaulipas. From the patients, sociodemographic data, clinical history and pharmacological treatments were obtained. From the physicians, sociodemographic and academic information were collected. Mean age of the patients was 63 ± 11 years and 31.7% were prescribed NSAIDs. When compare exposed versus non-exposed to NSAIDs, being in uncontrolled high blood pressure, uncontrolled hypertension, multimorbidity and polypharmacy. The variables associated to the prescription of NSAIDs were: uncontrolled hypertension, multimorbidity and polypharmacy. The 56.7% of the physicians were women, 83.3% with experience >10 years and 33.3% with current certification by the Council in Family Medicine. The inappropriate prescription of NSAIDs revealed the need to implement actions to mitigate the potential risk for the hypertension patients to present a complication.

Interconnections between the Gut Microbiome and Alzheimer's Disease: Mechanisms and Therapeutic Potential.

Alzheimer's disease (AD) is a neurodegenerative disease that is known to accumulate amyloid-β (Aβ) and tau protein. Clinical studies have not identified pathogenesis mechanisms or produced an effective cure for AD. The Aβ monoclonal antibody lecanemab reduces Aβ plaque formation for the treatment of AD, but more studies are required to increase the effectiveness of drugs to reduce cognitive decline. The lack of AD therapy targets and evidence of an association with an acute neuroinflammatory response caused by several bacteria and viruses in some individuals has led to the establishment of the infection hypothesis during the last 10 years. How pathogens cross the blood-brain barrier is highly topical and is seen to be pivotal in proving the hypothesis. This review summarizes the possible role of the gut microbiome in the pathogenesis of AD and feasible therapeutic approaches and current research limitations.