Therapeutic Potential Research Articles

Exploring the therapeutic potential of achyranthes aspera: A comprehensive review

Achyranthes aspera, commonly known as "Prickly Chaff Flower," is a medicinal plant extensively used in traditional medicine systems worldwide. This review provides a comprehensive overview of the phytochemical constituents, pharmacological properties, and therapeutic potential of Achyranthes aspera. The phytochemical analysis reveals the presence of various bioactive compounds such as alkaloids, flavonoids, saponins, and terpenoids, among others, which contribute to its medicinal properties. Pharmacological studies have demonstrated the diverse therapeutic effects of Achyranthes aspera, including anti-inflammatory, analgesic, antioxidant, antimicrobial, antidiabetic, hepatoprotective, and anticancer activities. Furthermore, the plant has been utilized in the management of various ailments such as arthritis, diabetes, respiratory disorders, gastrointestinal disorders, and skin diseases. However, despite its promising therapeutic potential, further research is warranted to elucidate the underlying mechanisms of action and evaluate its safety and efficacy for clinical applications. This review aims to consolidate the existing knowledge on Achyranthes aspera, providing insights for future research and potential development of novel therapeutic agents.

SYNTHESIS, CHARACTERIZATION & BIOLOGICAL EVALUATION OF SOME FLUOROQUINOLONE DERIVATIVES AS ANTIMICROBIAL AGENTS

Fluoroquinolones, a class of synthetic antibacterial agents, have gained significant attention due to their broad-spectrum activity against various bacterial pathogens. However, the emergence of resistance to conventional fluoroquinolones underscores the necessity for novel derivatives with enhanced efficacy and reduced resistance profiles. The synthesis of fluoroquinolone derivatives involves structural modifications aimed at improving antimicrobial activity, pharmacokinetic properties, and minimizing adverse effects. Various synthetic routes, including modification of the quinolone core structure, substitution of fluorine atoms, and introduction of diverse functional groups, have been explored to tailor the properties of these derivatives. Characterization techniques such as infrared spectroscopy (IR) has been employed to elucidate the chemical structures and confirm the purity of synthesized compounds. Biological evaluation encompasses in vitro and in vivo studies to assess the antimicrobial activity, cytotoxicity, and pharmacological profiles of fluoroquinolone derivatives. These evaluations provide crucial insights into the therapeutic potential, mechanism of action, and safety profile of novel compounds.

An article reviews of anti-cataract activity of hydroalcoholic extract of Annona squamosa leaves

Other medicines and natural remedies have been used for the treatment and health of people since ancient times. Medicinal plants are considered useful and of the most important purpose. It can be applied to botanical medicines, nutraceuticals, medicines, food products, cosmetics, etc. There is an increasing demand for. Custard apples. It is a versatile tree whose fruit is edible and a source of medicine and products. It is used as antioxidant, antidiabetic, hepatoprotective, cytotoxic activity, genotoxicity, antitumor activity, anti-inflammatory drug. Cataract is nothing but visual impairment caused by a defect in the lens. It is one of the causes of blindness worldwide; It accounts for approximately 42% of all blindness. One significant risk factor for the development of posterior subcapsular cataracts is long-term glucocorticoid usage. The preventive and therapeutic effects of many herbs such as onion, Chinese cinnamon and ginkgo, which have protective properties against cataracts, have been reported. This review demonstrates the therapeutic potential of custard apple leaf extract as an anti-cataract effec

Absence of Evidence for Sustained Effects of Daily Cannabidiol Administration on Anandamide Plasma Concentration in Individuals with Cocaine Use Disorder: Exploratory Findings from a Randomized Controlled Trial.

Background: Cannabidiol (CBD) has been proposed to have a therapeutic potential over a wide range of neuropsychiatric disorders, including substance use disorders. Pre-clinical evidence suggests that CBD can increase anandamide (AEA) plasma concentration, possibly mediating some of its therapeutic properties. Whether CBD exerts such an effect on AEA in individuals with cocaine use disorder (CUD) remains unknown. Aims: To explore the sustained effects of daily CBD administration on AEA plasma concentrations compared with placebo in CUD. Methods: We used data from a randomized, double-blind, placebo-controlled trial evaluating CBD's efficacy in CUD. Seventy-eight individuals were randomized to receive a daily oral dose of 800 mg CBD (n = 40) or a placebo (n = 38). Participants stayed in an inpatient detoxification setting for 10 days, after which they were followed in an outpatient setting for 12 weeks. AEA plasma concentration was measured at baseline and at 23-h post CBD ingestion on day 8 and week 4. A generalized estimating equation model was used to assess CBD's effects on AEA, and sensitivity analyses were computed using Bayesian linear regressions. Results: Sixty-four participants were included in the analysis. Similar mean AEA plasma concentrations in both treatment groups (p = 0.357) were observed. At day 8, mean AEA plasma concentrations (± standard deviation) were 0.26 (± 0.07) ng/mL in the CBD group and 0.29 (± 0.08) ng/mL in the placebo group (p = 0.832; Bayes factor [BF] = 0.190). At week 4, they were 0.27 (± 0.09) ng/mL in the CBD group and 0.30 (± 0.09) ng/mL in the placebo group (p = 0.181; BF = 0.194). Conclusion: While not excluding any potential acute and short-term effect, daily CBD administration did not exert a sustained impact on AEA plasma concentrations in individuals with CUD compared with placebo. Registration: clinicaltrials.gov (NCT02559167).

Functional Property and Regulatory Mechanism of Macrophages in Complementary and Alternative Medicine: From Bench to Clinic.

Complementary and alternative medicine (CAM) includes a wide range of treatments that are gaining acceptance among the public. It is increasingly being recognized as a viable option for treating various diseases with minimal side effects. Common avenues of this therapy include herbal medicine, acupuncture, physical exercise, aromatherapy, dietary therapy, and homeopathy etc. Macrophages are highly heterogeneous cells that play multiple regulatory roles. Practices such as herbal medicine, acupuncture, physical exercise, aromatherapy and dietary therapy exert curative effects by modulating the polarization status and the secretory phenotype of macrophages directly. Furthermore, herbal medicine, acupuncture, and physical exercise influence the crosstalk between macrophages and other types of cells, including cancer cells and T cells. Mechanistically, herbal medicine and acupuncture produce curative effects in diverse diseases, including inflammatory diseases and tumors, mainly by influencing the phosphorylation of signaling proteins in macrophages. Therefore, targeting macrophages offers theoretical support for advancing the scientific understanding of this therapy and aids in identifying potential therapeutic options. Hence, in this review, we systematically summarize the different regulations of macrophages in herbal medicine, acupuncture, physical exercise, aromatherapy, dietary therapy and homeopathy, and further highlight the therapeutic potential of targeting macrophages in complementary and alternative medicine.

Anti-neurofascin-155 antibody mediated a distinct phenotype of chronic inflammatory demyelinating polyradiculoneuropathy.

To investigate Ranvier's autoantibodies prevalence and isotypes in various peripheral neuropathy variants, compare clinical features between seronegative and seropositive patients, and elucidate immune mechanisms underlying antibody generation. Antibodies against anti-neurofascin-155 (NF155), NF186, contactin-1 (CNTN1), CNTN2, contactin-associated protein 1 (CASPR1), and CASPR2 were identified through cell-based assays. Plasma cytokines were analyzed in anti-NF155 antibody-positive chronic inflammatory demyelinating polyneuropathy (NF155+ CIDP) and Ranvier's antibodies-negative CIDP (Ab- CIDP) patients using a multiplexed fluorescent immunoassay, validated in vitro in a cell culture model. In 368 plasma samples, 50 Ranvier's autoantibodies were found in 45 individuals, primarily in CIDP cases (25 out of 69 patients) and in 10 out of 122 Guillain-Barré syndrome patients. Anti-NF155 and CNTN1-IgG were exclusive to CIDP. Fourteen samples were NF155-IgG, primarily IgG4 subclass, linked to CIDP features including early onset, tremor, sensory disturbance, elevated CSF protein, prolonged motor latency, conduction block, and poor treatment response. NF155-IgG had low sensitivity (20.28%) but high specificity (100%) for CIDP, rising to 88.88% with tremor and prolonged motor latency. Cytokine profiling in NF155+ CIDP revealed distinct immune responses involving helper T cells, toll-like receptor pathways. Some NF155+ CIDP patients had circulating NF155-specific B cells producing NF155-IgG without antigen presence, suggesting therapeutic potential. The study emphasizes the high specificity and sensitivity of NF155-IgG for diagnosing CIDP characterized by distinctive features. Further investigation into circulating NF155-specific B cell phenotypes may pave the way for B cell directed therapy.

The IL-12 family of heterodimeric cytokines in polycystic ovarian syndrome: biological role in induction, regulation, and treatment.

Polycystic ovary syndrome (PCOS) is a diverse endocrine disorder widely recognized as the prevailing metabolic condition among women in their reproductive years. The precise pathophysiological mechanisms underlying PCOS remain incompletely understood. However, existing evidence suggests that the development of PCOS may be linked to factors such as abdominal obesity, hyperandrogenism, and insulin resistance (IR). Excessive central adiposity in women with PCOS may lead to the development of a chronic, low-grade inflammation characterized by the activation of proinflammatory cytokines. The cytokines that belong to the IL-12 family are a collection of distinct heterodimeric cytokines that include IL-12, IL-23, IL-27, and IL-35. Recent research has provided further evidence regarding the significance of IL-12 cytokines in influencing both innate and adaptive immune responses in different diseases. Additionally, these studies have discovered diverse roles for certain members of the IL-12 family, encompassing multiple immunological functions that can either act as effectors or regulators. In this discourse, we examine the distinctive and atypical structural and functional attributes of this particular cytokine family. This study aims to offer a comprehensive overview of the pathophysiological significance of the IL-12 family cytokines in PCOS patients. Additionally, the therapeutic potential of the cytokines as novel approaches for PCOS treatment will be proposed.

The Therapeutic Potential of Harpagophytum procumbens and Turnera subulata and Advances in Nutraceutical Delivery Systems in Neurodegenerative Diseases

This review article covers the therapeutic potential of the plants Harpagophytum procumbens and Turnera subulata in the treatment of neurodegenerative diseases. Despite the recognition of their beneficial properties, there is notable shortage of specific clinical and in vitro studies on these species regarding neurodegenerative diseases. Compounds such as harpagosides and vite-xin-2-O-rhamnoside, found in Harpagophytum procumbens and Turnera subulata, respectively, as well as other antioxidants and anti-inflammatory agents, are associated with mechanisms of action that involve reducing oxidative stress and modulating the inflammatory response, indicating their therapeutic potential in these pathologies. Additionally, the use of nutraceuticals derived from medicinal plants has emerged as a promising approach, offering natural therapeutic alternatives. However, the pressing need for studies focusing on the pharmacokinetics, safety, and pharmacological interactions of these extracts for the treatment of neurodegenerative diseases is emphasized. This review also evaluated advances in nutraceutical delivery systems, highlighting technological innovations that can optimize the precise delivery of these compounds to patients. Such findings highlight the gaps in the study of these plants for the treatment of neurodegenerative diseases and, at the same time, the potential for opening new perspectives in the treatment of neurodegenerative diseases, providing expectations for innovative solutions in this critical domain of medicine.

Integrating single cell expression quantitative trait loci summary statistics to understand complex trait risk genes

Transcriptome-wide association study (TWAS) is a popular approach to dissect the functional consequence of disease associated non-coding variants. Most existing TWAS use bulk tissues and may not have the resolution to reveal cell-type specific target genes. Single-cell expression quantitative trait loci (sc-eQTL) datasets are emerging. The largest bulk- and sc-eQTL datasets are most conveniently available as summary statistics, but have not been broadly utilized in TWAS. Here, we present a new method EXPRESSO (EXpression PREdiction with Summary Statistics Only), to analyze sc-eQTL summary statistics, which also integrates 3D genomic data and epigenomic annotation to prioritize causal variants. EXPRESSO substantially improves existing methods. We apply EXPRESSO to analyze multi-ancestry GWAS datasets for 14 autoimmune diseases. EXPRESSO uniquely identifies 958 novel gene x trait associations, which is 26% more than the second-best method. Among them, 492 are unique to cell type level analysis and missed by TWAS using whole blood. We also develop a cell type aware drug repurposing pipeline, which leverages EXPRESSO results to identify drug compounds that can reverse disease gene expressions in relevant cell types. Our results point to multiple drugs with therapeutic potentials, including metformin for type 1 diabetes, and vitamin K for ulcerative colitis.

A novel signature incorporating genes related to lipid metabolism and immune for prognostic and functional prediction of breast cancer.

Breast cancer prognosis and functioning have not been thoroughly examined in relation to immunological and lipid metabolism. However, there is a lack of prognostic and functional analyses of the relationship between lipid metabolism and immunity in breast cancer. DEGs in breast cancer were obtained from UCSC database, and lipid metabolism and immune-related genes were obtained from GSEA and Immune databases. A predictive signature was constructed using univariate Cox and LASSO regression on lipid metabolism and immune-related DEGs. The signature's prognostic significance was assessed using Kaplan-Meier, time-dependent ROC, and risk factor survival scores. Survival prognosis, therapeutic relevance, and functional enrichment were used to mine model gene biology. We selected IL18, which has never been reported in breast cancer before, in the signature to learn more about its function, potential to predict outcome, and immune system role. RT-PCR was performed to verify the true expression level of IL18. A total of 136 DEGs associated with breast cancer responses to both immunity and lipid metabolism. Nine key genes (CALR, CCL5, CEPT, FTT3, CXCL13, FLT3, IL12B, IL18, and IL24, p < 1.6e-2) of breast cancer were identified, and a prognostic was successfully constructed with a good predictive ability. IL18 in the model also had good clinical prognostic guidance value and immune regulation and therapeutic potential. Furthermore, the expression of IL18 was higher than that in paracancerous tissue. A unique predictive signature model could effectively predict the prognosis of breast cancer, which can not only achieve survival prediction, but also screen out key genes with important functional mechanisms to guide clinical drug experiments.

Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer

Therapeutic resistance represents a bottleneck to treatment in advanced gastric cancer (GC). Ferroptosis is an iron-dependent form of non-apoptotic cell death and is associated with anti-cancer therapeutic efficacy. Further investigations are required to clarify the underlying mechanisms. Ferroptosis-resistant GC cell lines are constructed. Dysregulated mRNAs between ferroptosis-resistant and parental cell lines are identified. The expression of SOX13/SCAF1 is manipulated in GC cell lines where relevant biological and molecular analyses are performed. Molecular docking and computational screening are performed to screen potential inhibitors of SOX13. We show that SOX13 boosts protein remodeling of electron transport chain (ETC) complexes by directly transactivating SCAF1. This leads to increased supercomplexes (SCs) assembly, mitochondrial respiration, mitochondrial energetics and chemo- and immune-resistance. Zanamivir, reverts the ferroptosis-resistant phenotype via directly targeting SOX13 and promoting TRIM25-mediated ubiquitination and degradation of SOX13. Here we show, SOX13/SCAF1 are important in ferroptosis-resistance, and targeting SOX13 with zanamivir has therapeutic potential.

Exosomes derived from TNF-α-treated bone marrow mesenchymal stem cells ameliorate myocardial infarction injury in mice

ABSTRACT Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) exhibit considerable therapeutic potential for myocardial regeneration. In our investigation, we delved into their impact on various aspects of myocardial infarction (MI), including cardiac function, tissue damage, inflammation, and macrophage polarization in a murine model. We meticulously isolated the exosomes from TNF-α-treated BMSCs and evaluated their therapeutic efficacy in a mouse MI model induced by coronary artery ligation surgery. Our comprehensive analysis, incorporating ultrasound, serum assessment, Western blot, and qRT-PCR, revealed that exosomes from TNF-α-treated BMSCs demonstrated significant therapeutic potential in reducing MI-induced injury. Treatment with these exosomes resulted in improved cardiac function, reduced infarct area, and increased left ventricular wall thickness in MI mice. On a mechanistic level, exosome treatment fostered M2 macrophage polarization while concurrently suppressing M1 polarization. Hence, exosomes derived from TNF-α-treated BMSCs emerge as a promising therapeutic strategy for alleviating MI injury in a mouse model.

ADVANCEMENTS IN UNDERSTANDING THE MOLECULAR MECHANISMS REGULATING URIC ACID METABOLISM IN THE INTESTINE

This review provides contemporary insights into the direct and indirect pathogenetic connections between purine compound metabolism and biochemical processes within the cells of the gastrointestinal system. A thorough analysis of recent publications from 2000 to 2024, sourced from databases including Scopus, PubMed, eLIIBRARY, and Google Scholar, was conducted. Uric acid serves as the end product of purine-containing compound catabolism. Its concentration is intricately regulated through the collaboration of the kidneys and gastrointestinal organs, namely the small intestine and liver. Gout, a chronic condition, emerges from the interplay between molecular genetic factors and external influences. Elevated levels of urates in the blood serum (hyperuricemia) and the deposition of sodium urate crystals in organs and tissues set off a cascade of inflammatory and fibrotic processes within mucosal, smooth muscle, parenchymal, and endothelial cells, including those within the gastrointestinal tract. Normally, a person excretes about 1.5 g of uric acid per day. Under physiological conditions, two-thirds of uric acid is excreted from the body by the kidneys, one-third through the intestines, and a small part is excreted with bile. The hypothesis that links the pathogenesis of hyperuricemia with “renal overload” suggests that the disease may develop as a result of impaired renal excretion with insufficient elimination of uric acid through the intestines. Part of uric acid transport systems actively works in hepatocytes and enterocytes, which determines its formation and clearance. Uric acid transporter proteins are divided into two categories: urate reabsorption transporters and urate excretion transporters, their expression is regulated by transcription factors, hormones and metabolites of intestinal microflora. The influence of intestinal microbiota on uric acid metabolism is related to its participation in purine metabolism, decomposition and elimination of uric acid with metabolites of intestinal flora and inhibition of gouty inflammation and is evaluated as a new therapeutic potential in gout and hyperuricemia, which allows to avoid kidney damage and urolithiasis.

Role of Culinary Indian Spices in the Regulation of TGF-β Signaling Pathway in Inflammation-Induced Liver Cancer.

Hepatocellular carcinoma (HCC) results from various etiologies, such as Hepatitis B and C, Alcoholic and Non-alcoholic fatty liver disorders, fibrosis, and cirrhosis. About 80 to 90% of HCC cases possess cirrhosis, which is brought on by persistent liver inflammation. TGF-β is a multifunctional polypeptide molecule that acts as a pro-fibrogenic marker, inflammatory cytokine, immunosuppressive agent, and pro-carcinogenic growth factor during the progression of HCC. The preclinical and clinical evidence illustrates that TGF-β can induce epithelial-to-mesenchymal transition, promoting progression and hepatocyte immune evasion. Therefore, targeting the TGF-β pathway can be a promising therapeutic option against HCC. We carry out a systemic analysis of eight potentially selected culinary Indian spices: Turmeric, Black pepper, Ginger, Garlic, Fenugreek, Red pepper, Clove, Cinnamon, and their bioactives in regulation of the TGF-β pathway against liver cancer. Turmeric and its active constituent, curcumin, possess the highest therapeutic potential in treating inflammation-induced HCC and they also have the maximum number of ongoing in-vivo and in-vitro studies.

Deciphering the Role of microRNAs: Unveiling Clinical Biomarkers and Therapeutic Avenues in Atrial Fibrillation and Associated Stroke—A Systematic Review

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression by binding to target messenger RNAs (mRNAs). miRNAs have been implicated in a variety of cardiovascular and neurological diseases, such as myocardial infarction, cardiomyopathies of various geneses, rhythmological diseases, neurodegenerative illnesses and strokes. Numerous studies have focused on the expression of miRNA patterns with respect to atrial fibrillation (AF) or acute ischemic stroke (AIS) However, only a few studies have addressed the expression pattern of miRNAs in patients with AF and AIS in order to provide not only preventive information but also to identify therapeutic potentials. Therefore, the aim of this review is to summarize 18 existing manuscripts that have dealt with this combined topic of AF and associated AIS in detail and to shed light on the most frequently mentioned miRNAs-1, -19, -21, -145 and -146 with regard to their molecular mechanisms and targets on both the heart and the brain. From this, possible diagnostic and therapeutic consequences for the future could be derived.

A GITRL-mTORC1-GM-CSF Positive Loop Promotes Pathogenic Th17 Response in Primary Sjögren Syndrome.

Glucocorticoid-induced tumor necrosis factor receptor superfamily-related protein (GITR), with its ligand (GITRL), plays an important role in CD4+ T cell-mediated autoimmunity. This study aimed to investigate the underlying mechanisms of GITRL in primary Sjögren syndrome (pSS). Patients with pSS and healthy controls were recruited. Serum GITRL and Th17-related cytokines were determined. RNA sequencing was performed to decipher key signal pathways. Nonobese diabetes (NOD) mice were adopted as experimental Sjögren models and recombinant adeno-associated virus (rAAV) transduction was conducted to verify the therapeutic potentials of targeting GITRL in vivo. Serum GITRL was significantly higher in patients with pSS and showed a positive correlation with leukopenia, thrombocytopenia, autoantibodies, lung involvement, and disease activity. Serum GITRL was correlated with Th17-related cytokines. GITRL promoted the expansion of Th17 and Th17.1 cells. Expansion of granulocyte-macrophage colony-stimulating factor positive (GM-CSF+) CD4+ T cells induced by GITRL could be inhibited by blockade of GITRL. Moreover, GM-CSF could stimulate GITRL expression on monocytes. RNA sequencing revealed mammalian target of rapamycin complexes 1 (mTORC1) might be the key modulator. The increased phosphorylation of S6 and STAT3 and the expansion of Th17 and Th17.1 cells induced by GITRL were effectively inhibited by rapamycin, suggesting a GITRL-mTORC1-GM-CSF positive loop in pathogenic Th17 response in pSS. Administration of an rAAV vector expressing short hairpin RNA targeting GITRL alleviated disease progression in NOD mice. Our results identified the pathogenic role of GITRL in exacerbating disease activity and promoting pathogenic Th17 response in pSS through a GITRL-mTORC1-GM-CSF loop. These findings suggest GITRL might be a promising therapeutic target in the treatment of pSS.

Unlocking the therapeutic potential of TRPV3: Insights into thermosensation, channel modulation, and skin homeostasis involving TRPV3.

Recent insights reveal the significant role of TRPV3 in warmth sensation. A novel finding elucidated how thermosensation is affected by TRPV3 membrane abundance that is modulated by the transmembrane protein TMEM79. TRPV3 is a warmth-sensitive ion channel predominantly expressed in epithelial cells, particularly skin keratinocytes. Multiple studies investigated the roles of TRPV3 in cutaneous physiology and pathophysiology. TRPV3 activation by innocuous warm temperatures in keratinocytes highlights its significance in temperature sensation, but whether TRPV3 directly contributes to warmth sensations in vivo remains controversial. This review explores the electrophysiological and structural properties of TRPV3 and how modulators affect its intricate regulatory mechanisms. Moreover, we discuss the multifaceted involvement of TRPV3 in skin physiology and pathology, including barrier formation, hair growth, inflammation, and itching. Finally, we examine the potential of TRPV3 as a therapeutic target for skin diseases and highlight its diverse role in maintaining skin homeostasis.

Exosomes enriched by miR-429-3p derived from ITGB1 modified Telocytes alleviates hypoxia-induced pulmonary arterial hypertension through regulating Rac1 expression

BackgroundRecent studies have emphasized the critical role of Telocytes (TCs)-derived exosomes in organ tissue injury and repair. Our previous research showed a significant increase in ITGB1 within TCs. Pulmonary Arterial Hypertension (PAH) is marked by a loss of microvessel regeneration and progressive vascular remodeling. This study aims to investigate whether exosomes derived from ITGB1-modified TCs (ITGB1-Exo) could mitigate PAH.MethodsWe analyzed differentially expressed microRNAs (DEmiRs) in TCs using Affymetrix Genechip miRNA 4.0 arrays. Exosomes isolated from TC culture supernatants were verified through transmission electron microscopy and Nanoparticle Tracking Analysis. The impact of miR-429-3p-enriched exosomes (Exo-ITGB1) on hypoxia-induced pulmonary arterial smooth muscle cells (PASMCs) was evaluated using CCK-8, transwell assay, and inflammatory factor analysis. A four-week hypoxia-induced mouse model of PAH was constructed, and H&E staining, along with Immunofluorescence staining, were employed to assess PAH progression.ResultsForty-five miRNAs exhibited significant differential expression in TCs following ITGB1 knockdown. Mus-miR-429-3p, significantly upregulated in ITGB1-overexpressing TCs and in ITGB1-modified TC-derived exosomes, was selected for further investigation. Exo-ITGB1 notably inhibited the migration, proliferation, and inflammation of PASMCs by targeting Rac1. Overexpressing Rac1 partly counteracted Exo-ITGB1’s effects. In vivo administration of Exo-ITGB1 effectively reduced pulmonary vascular remodeling and inflammation.ConclusionsOur findings reveal that ITGB1-modified TC-derived exosomes exert anti-inflammatory effects and reverse vascular remodeling through the miR-429-3p/Rac1 axis. This provides potential therapeutic strategies for PAH treatment.Graphical 1. Identification of Differentially Expressed microRNAs (DEmiRs) in ITGB1 overexpressed TCs.2. Effects of Exo-ITGB1 or miR-429-3p on Hypoxia-Induced PASMCs in vitro.3. Exo-ITGB1 inhibits the hyper-proliferation and migration of PASMCs through regulating miR-429-3p/Rac1 axis in vitro.4. The therapeutic potential of Exo-ITGB1 in hypoxia-induced PAH model in vivo.

Oxytocin, but not vasopressin, decreases willingness to harm others by promoting moral emotions of guilt and shame.

Prosocial and moral behaviors have overlapping neural systems and can both be affected in a number of psychiatric disorders, although whether they involve similar neurochemical systems is unclear. In the current registered randomized placebo-controlled trial on 180 adult male and female subjects, we investigated the effects of intranasal administration of oxytocin and vasopressin, which play key roles in influencing social behavior, on moral emotion ratings for situations involving harming others and on judgments of moral dilemmas where others are harmed for a greater good. Oxytocin, but not vasopressin, enhanced feelings of guilt and shame for intentional but not accidental harm and reduced endorsement of intentionally harming others to achieve a greater good. Neither peptide influenced arousal ratings for the scenarios. Effects of oxytocin on guilt and shame were strongest in individuals scoring lower on the personal distress subscale of trait empathy. Overall, findings demonstrate for the first time that oxytocin, but not vasopressin, promotes enhanced feelings of guilt and shame and unwillingness to harm others irrespective of the consequences. This may reflect associations between oxytocin and empathy and vasopressin with aggression and suggests that oxytocin may have greater therapeutic potential for disorders with atypical social and moral behavior.

Amlodipine Protects against Methotrexate-Induced Acute Kidney Injury in Rats

Background Methotrexate (MTX) is a commonly used chemotherapy drug with known nephrotoxic effects, including the potential for acute kidney injury. However, the precise mechanism through which MTX induces nephrotoxicity remains unclear, though oxidative stress and direct toxic effects on renal tubules are believed to play key roles. Recent studies suggest that calcium channel blockers may offer promise in slowing down the progression of chronic kidney diseases. Objective The purpose of this study was to explore the potential of Amlodipine, a calcium channel blocker, to alleviate acute kidney injury caused by the administration of MTX in rats. Methods Three groups of twenty-four male Wistar rats were randomly assigned: Group 1—the control group was given normal saline orally. Group II, underwent five days of continuous administration of a single intraperitoneal (IP) dosage of 20 mg/kg MTX. The same dosage of MTX was given to Group III followed by an oral dose of Amlodipine at 5 mg/kg over the same period. Upon completion of the experiment, serum biochemical parameters, renal damage markers, oxidative stress, inflammatory markers, and kidney tissue histology were assessed. Results The results indicate that MTX administration significantly increased the levels of serum biochemical parameters, renal damage markers, inflammatory markers, oxidative stress markers, and induced alterations in kidney histology. However, the administration of Amlodipine following MTX treatment protected against these changes. Conclusion Amlodipine exhibits therapeutic potential in mitigating MTX-induced kidney injury in rats and its associated side effects.