Anti-apoptotic Effects Research Articles

Linalool may have a therapeutic effect on cadmium-induced nephrotoxicity by regulating NF-κB/TNF and GRP78/CHOP signaling pathways

Cadmium (Cd) is an environmental pollutant heavy metal with nephrotoxic effect. One of the primary constituents of essential oils is Linalool (Lin), a monoterpene having a variety of pharmacological properties including antimicrobial, anti-inflammatory, and antioxidant effects. The purpose of this study was to ascertain how Lin affected endoplasmic reticulum stress (ERS) and pro-inflammatory mediators in Cd-induced nephrotoxicity. In the experiment, 28 male rats were randomly divided into four equal groups as control (no application), Cd (Cd at a dose of 3 mg/kg for the first 7 days), Cd+Lin (Cd at a dose of 3 mg/kg for the first 7 days and 100 mg/kg/day Lin) and Lin (100 mg/kg/day Lin) (n=7). The experiment was completed on the 15th day after all treatments were performed. Blood serum and kidney tissue samples were used for analyses. Cd-induced histopathological changes, inflammation, oxidative stress, and apoptosis were determined to increase in kidney tissue. However, it was observed that Cd-induced adverse effects in kidney tissue were mainly eliminated by Lin treatment. In conclusion, Lin demonstrated anti-inflammatory, anti-oxidant and anti-apoptotic effects in Cd-induced nephrotoxicity. Therefore, we believe that Lin may represent a high potential therapeutic strategy against renal tissue damage.

Topical frankincense treatment for frostbite based on microcirculation improvements

Ethnopharmacological relevanceThe Chinese traditional medicine frankincense, which can promote blood circulation, is often used to treat skin lesions, including frostbite. Aim of the studyTo explore the properties of frankincense oil extract (FOE) and its active ingredients and their effect on frostbite wound recovery as an approach to understand the mechanism associated with microcirculation-improvement therapy. Materials and methodsThe microcirculation-improving effects of FOE and its active ingredients were evaluated using liquid nitrogen-induced frostbite animal models. The rewarming capacity of FOE on the skin was determined through infrared detection, and frostbite wound healing was evaluated following haematoxylin and eosin (H&E) staining and fibre analysis. Moreover, related factors were examined to determine the anti-apoptotic, anti-inflammatory, and microcirculatory properties of FOE and its active ingredients on affected tissue in the context of frostbite. ResultsFOE and its active ingredients rapidly rewarmed wound tissue after frostbite by increasing the temperature. Moreover, these treatments improved wound healing and restored skin structure through collagen and elastin fibre remodelling. In addition, they exerted anti-apoptotic effects by decreasing the number of apoptotic cells, reducing caspase-3 expression, and eliciting anti-inflammatory effects by decreasing COX-2 and β-catenin expression. They also improved microcirculatory disorders by decreasing HIF-1α expression and increasing CD31 expression. ConclusionsFOE and its active components can effectively treat frostbite by enhancing microcirculation, inhibiting the infiltration of inflammatory cells, decreasing cell apoptosis, and exerting antinociceptive effects. These findings highlight FOE as a new treatment option for frostbite, providing patients with an effective therapeutic strategy.

Propolis: a natural compound with potential as an adjuvant in cancer therapy - a review of signaling pathways.

Propolis is a natural product used in cancer treatment, which is produced by bees via different sources. The chemical composition of Propolis is determined based on the climatic and geographical conditions, as well as harvesting time and method. This compound has been the subject of numerous investigational endeavors due to its expansive therapeutic capacity which includes antibacterial, anti-fungal, anti-inflammatory, anti-oxidant, anti-viral, and anti-cancer effects. The growing incidence rate of different cancers necessitates the need for developing novel preventive and therapeutic strategies. Chemotherapy, radiotherapy, and stem cell therapy have proved effective in cancer treatment, regardless of the adverse events associated with these modalities. Clinical application of natural compounds such as Propolis may confer promise as an adjuvant therapeutic intervention, particularly in certain subpopulations of patients that develop adverse events associated with anticancer regimens. The diverse biologically active compounds of propolis are believed to confer anti-cancer potential by modulation of critical signaling cascades such as caffeic acid phenethyl ester, Galangin, Artepillin C, Chrysin, Quercetin, Caffeic acid, Nymphaeols A and C, Frondoside A, Genistein, p-coumaric acid, and Propolin C. This review article aims to deliver a mechanistic account of anti-cancer effects of propolis and its components. Propolis can prevent angiogenesis by downregulating pathways involving Jun-N terminal kinase, ERK1/2, Akt and NF-ƘB, while counteracting metastatic progression of cancer by inhibiting Wtn2 and FAK, and MAPK and PI3K/AKT signaling pathways. Moreover, propolis or its main components show regulatory effects on cyclin D, CDK2/4/6, and their inhibitors. Additionally, propolis-induced up-regulation of p21 and p27 may result in cell cycle arrest at G2/M or G0/G1. The broad anti-apoptotic effects of propolis are mediated through upregulation of TRAIL, Bax, p53, and downregulation of the ERK1/2 signaling pathway. Considering the growing body of evidence regarding different anti-cancers effects of propolis and its active components, this natural compound could be considered an effective adjuvant therapy aimed at reducing related side effects associated with chemotherapy and radiotherapy.

New Insights into D-Aspartate Signaling in Testicular Activity.

D-aspartate (D-Asp) is an amino acid found in high concentrations in the testis and pituitary gland. Increasing evidence suggests that D-Asp promotes spermatogenesis by activating testosterone production in the Leydig cells via LH release from the pituitary gland. In vitro studies indicate that D-Asp may also influence steroidogenesis and spermatogenesis through autocrine and paracrine signals. D-Asp enhances StAR and steroidogenic enzyme expressions, facilitating testicular cell proliferation via the GluR/ERK1/2 pathway. Moreover, it supports spermatogenesis by enhancing the mitochondrial function in spermatocytes, aiding in the metabolic shift during meiosis. Enhanced mitochondrial function, along with improved MAM stability and reduced ER stress, has been observed in Leydig and Sertoli cells treated with D-Asp, indicating potential benefits in steroidogenesis and spermatogenesis efficiency. Conversely, D-Asp exerts a notable anti-apoptotic effect in the testis via the AMPAR/AKT pathway, potentially mediated by antioxidant enzyme modulation to mitigate testicular oxidative stress. This review lays the groundwork for future investigations into the molecules promoting spermatogenesis by stimulating endogenous testosterone biosynthesis, with D-amino acids emerging as promising candidates.

Protective effect of irbesartan against hepatic ischemia-reperfusion injury in rats: role of ERK, STAT3, and PPAR-γ inflammatory pathways in rats.

This study aimed to elucidate the possible hepatocellular protective role of irbesartan during hepatic ischemia-reperfusion injury (HIRI) and the probable underlying mechanisms. Wistar rats were allocated into four groups: sham; HIRI (control); irbesartan (50 mg/kg) + HIRI; irbesartan (100 mg/kg) + HIRI; irbesartan + GW9662 (1 mg/kg, i.p.) + HIRI. Rats pretreated orally with irbesartan or vehicle for 14 days underwent 45-min hepatic ischemia followed by 60-min reperfusion. Irbesartan preconditioning diminished alanine transaminase (ALT) and aspartate transaminase (AST) serum levels, and reduced extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 (STAT3). Irbesartan decreased proapoptotic BAX (bcl-2-like protein 4), increased anti-apoptotic B-cell lymphoma 2 (BCL2) hepatic content, and thereby reduced BAX/BCL2 ratio. Moreover, irbesartan preconditioning reduced autophagy-related proteins Beclin1 and LC3 II, and elevated p62 (protein responsible for autophagosome degradation). It elevated proliferator-activated receptor γ (PPAR-γ), and reduced tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) hepatic gene expression. Also, hepatic protein expressions of nuclear factor kappa-B p65 (NF-κB p65) and caspase-3 were lessoned by irbesartan pretreatment in HIRI rats. However, GW9662 abrogated irbesartan's effect on HIRI. The protective effect of irbesartan on HIRI may be mediated by alleviation of ERK, STAT3, and PPAR-γ inflammatory pathways, exerting anti-apoptotic and anti-autophagic effects in HIRI in rats.

Dysregulation of lipid metabolism in chronic kidney disease and the role of natural products.

Dysregulation of lipid metabolism plays a key role in the onset and progression of CKD, and a thorough understanding of its regulatory mechanisms is essential for the development of effective treatments. In recent years, an increasing number of studies have focused on the pharmacological activities of natural products and their application in the treatment of chronic diseases. Natural products, including plant extracts and bioactive compounds, have been shown to exert anti-inflammatory, antioxidant, antifibrosis, and anti-apoptotic effects through various signaling pathways in the treatment of CKD. Many natural products have been shown to target dysregulated lipid metabolism through various signaling pathways. This review summarizes the key regulatory factors and signaling pathways involved in the dysregulation of lipid metabolism in chronic kidney disease (CKD), highlighting their importance as potential therapeutic targets. Recently published research on the potential therapeutic benefits of natural products for the treatment of CKD was described. These studies have revealed the multi-target role of natural products in the regulation of lipid metabolism. Natural products show great potential in targeting lipid metabolism-related pathways, offering a novel research direction for the treatment of CKD while providing a scientific basis and experimental support for the development of new treatment strategies.

Nesfatin-1: A Novel Diagnostic and Prognostic Biomarker in Digestive Diseases.

Nesfatin-1, deriving from a precursor protein, NUCB2, is a newly discovered molecule with anti-apoptotic, anti-inflammatory, antioxidant, and anorexigenic effects. It was initially identified in the central nervous system (CNS) and received increasing interest due to its energy-regulating properties. However, research showed that nesfatin-1 is also expressed in peripheral tissues, including the digestive system. The aim of this review is to give a résumé of the present state of knowledge regarding its structure, immunolocalization, and potential implications in diseases with inflammatory components. The main objective was to focus on its clinical importance as a diagnostic biomarker and potential therapeutic molecule in a variety of disorders, among which digestive disorders were of particular interest. Previous studies have shown that nesfatin-1 regulates the balance between pro- and antioxidant agents, which makes nesfatin-1 a promising therapeutic agent. Further in-depth research regarding the underlying mechanisms of action is needed for a better understanding of its effects.

Mitigating diabetes-related complications: Empowering metformin with cholecalciferol and taurine supplementation in type 2 diabetic rats.

Type 2 diabetes is one of the most prevalent chronic diseases worldwide, significantly impacting patients' quality of life. Current treatment options like metformin (MET) effectively counteract hyperglycemia but fail to alleviate diabetes-associated complications such as retinopathy, neuropathy, nephropathy, hepatopathy, and cardiovascular diseases. To propose the supplementation of cholecalciferol (CHO) and taurine (TAU) to enhance MET efficacy in controlling diabetes while minimizing the risk of associated complications. The study involved sixty rats, including ten non-diabetic control rats and fifty experimental rats with type 2 diabetes induced by streptozotocin. The experimental rats were further subdivided into positive control and treatment subgroups. The four treatment groups were randomly allocated to a single MET treatment or MET combined with supplements either CHO, TAU, or both. Diabetic rats exhibited elevated levels of glucose, insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), glycated hemoglobin%, lipid markers, aspartate aminotransferase, and malondialdehyde, along with reduced levels of antioxidant enzymes (catalase and superoxide dismutase). The administration of CHO and TAU supplements alongside MET in diabetic rats led to a noticeable recovery of islet mass. The antioxidative, anti-inflammatory, and anti-apoptotic properties of the proposed combination therapy significantly ameliorated the aforementioned abnormalities. The supplementation of CHO and TAU with MET showed the potential to significantly improve metabolic parameters and protect against diabetic complications through its antioxidative, anti-inflammatory, and anti-apoptotic effects.

Influence of Metamizole on Antitumour Activity of Risedronate Sodium in In Vitro Studies on Canine (D-17) and Human (U-2 OS) Osteosarcoma Cell Lines.

The availability of metamizole varies greatly around the world. There are countries such as the USA, UK, or Australia where the use of metamizole is completely forbidden, and there are also countries where this drug is available only on prescription (e.g., Greece, Italy, Spain, etc.) and those in which it is sold OTC-over the counter (e.g., most Asian and South American countries). Metamizole, as a drug with a strong analgesic effect, is used as an alternative to other non-steroidal anti-inflammatory drugs, alone or in combination with opioid drugs. Risedronate sodium is a third-generation bisphosphonate commonly used in orthopaedic and metabolic diseases of the musculoskeletal system, including hypercalcemia, postmenopausal osteoporosis, Paget's disease, etc. The aim of this study was to check whether there were any pharmacological interactions between metamizole and risedronate sodium in in vitro studies. Cell viability was assessed using the MTT method, the number of apoptotic cells was assessed using the labelling TUNEL method, and the cell cycle assessment was performed with a flow cytometer and propidium iodide. This was a pilot study, which is why only two cancer cell lines were tested: D-17 of canine osteosarcoma and U-2 OS of human osteosarcoma. Exposure of the canine osteosarcoma cell line to a combination of risedronate sodium (100 µg/mL) and metamizole (50, 5, and 0.5 µg/mL) resulted in the complete abolition of the cytoprotective activity of metamizole. In the human osteosarcoma cell line, the cytotoxic effect of risedronate sodium was entirely eliminated in the presence of 50 µg/mL of metamizole. The cytoprotective and anti-apoptotic effect of metamizole in combination with risedronate sodium in the tested human and canine osteosarcoma cell lines indicates an urgent need for further in vivo studies to confirm or disprove the potential dose-dependent undesirable effect of such a therapy.

Hinokiflavone exerts dual regulation on apoptosis and pyroptosis via the SIX4/Stat3/Akt pathway to alleviate APAP-induced liver injury

Hinokiflavone (HF), classified as a flavonoid, is a main bioactive compound in Platycladus orientalis and Selaginella. HF exhibits activities including anti-HIV, anti-inflammatory, antiviral, antioxidant and anti-tumor effects. The study aimed to explore the function and the mechanisms of HF on acetaminophen (APAP)-induced acute liver injury. Results indicated that HF treatment mitigated the impact of APAP on viability and restored levels of MDA, GSH and SOD on HepG2 cells. The accumulation of reactive oxygen species (ROS) mitochondrial membrane potential (MMP) in HepG2 cells stimulated by APAP were also blocked by HF. HF reduced the levels of pro-apoptotic and pro-pyroptotic proteins. Flow cytometry analysis and fluorescence staining results were consistent with western blot analysis. Following HF treatment in the APAP-induced cell model, there was observed an augmentation in the phosphorylation of Stat3 and an increase in the expression of SIX4. However, not only silenced the SIX4 protein in HepG2 cells by siRNA, but also adding the Stat3 inhibitor (Stattic), attenuated the anti-apoptotic and anti-pyroptotic effects of HF significantly. Furthermore, HF alleviated liver damage in C57BL/6 mice model. Overall, our study demonstrated that HF mitigates apoptosis and pyroptosis induced by APAP in drug-induced liver injury (DILI) through the SIX4/Akt/Stat3 pathway in vivo and in vitro. HF may have promising potential for for the treatment of DILI.

Genetic modification of primary human B cells to model the process of B cell development in germinal centers

The main stages of maturation of antigen-specific B cells occur in the germinal centers of the lymph nodes. During the process of differentiation, a decision is made on which path the B cells will take to develop further. They will either turn into short-lived plasmablasts or memory B cells or plasma cells. The relationship between these processes is very important for the development of a productive humoral immune response. The goal of the work was to create a system that is capable of simulating ex vivo processes occurring in germinal centers. We used primary B cells from human peripheral blood as starting material. B lymphocytes were stimulated in vitro using feeder cells carrying CD40L molecules and recombinant IL-21. Upon IL-21/CD40L stimulation, B lymphocytes changed their morphology, surface phenotype, and functional activity. After active expansion for 10 days, further cell growth stopped, and after some time they died. To generate stably proliferating B cells, we used lentiviral transduction of IL-21/CD40L stimulated IgM+ B cells. For this purpose, lentivirus preparations were obtained that carried a cassette consisting of the BCL6 and BCL2L1 genes, separated by a sequence encoding the self-cutting peptide P2A, as well as a GFP reporter gene separated from the target genes by an IRES element. The cassette used ensured the synthesis of the Bcl-6 transcription factor and the Bcl-XL protein in target cells. The Bcl-6 repressor prevented B cells from undergoing terminal differentiation and becoming plasma cells, and the Bcl-XL protein had an anti-apoptotic effect. Transduced B cells proliferated for more than a month and maintained a plasmablast phenotype. Forty-two days after the start of stimulation, transduced B cells remained GFP-positive, coexpressed CD27 and CD38 antigens, carried surface CD20 and IgM, intracellular Bcl-6, Bcl-XL and IgM, retained IgM secretion, but remained negative for surface and intracellular IgG. The proven stimulation system will allow us to simulate key aspects of B cell development in germinal centers to study the formation of B cell memory, which will ultimately facilitate the development of effective vaccines.

Pharmacological mechanisms by which baicalin ameliorates cardiovascular disease.

Baicalin is a flavonoid glycoside obtained from the dried root of Scutellaria baicalensis Georgi, which belongs to the Labiatae family. Accumulating evidence indicates that baicalin has favorable therapeutic effects on cardiovascular diseases. Previous studies have revealed the therapeutic effects of baicalin on atherosclerosis, myocardial ischemia/reperfusion injury, hypertension, and heart failure through anti-inflammatory, antioxidant, and lipid metabolism mechanisms. In recent years, some new ideas related to baicalin in ferroptosis, coagulation and fibrinolytic systems have been proposed, and new progress has been made in understanding the mechanism by which baicalin protects cardiomyocytes. However, many relevant underlying mechanisms remain unexplained, and much experimental data is lacking. Therefore, further research is needed to determine these mechanisms. In this review, we summarize the mechanisms of baicalin, which include its anti-inflammatory and antioxidant effects; inhibition of endothelial cell apoptosis; modulation of innate immunity; suppression of vascular smooth muscle cells proliferation, migration, and contraction; regulation of coagulation and fibrinolytic systems; inhibition of myocardial hypertrophy; prevention of myocardial fibrosis; and anti-apoptotic effects on cardiomyocytes.

The caspase-inhibitor Emricasan efficiently counteracts cisplatin- and neomycin-induced cytotoxicity in cochlear cells

Cisplatin is a chemotherapeutic agent widely used to treat solid tumors. However, it can also be highly ototoxic, resulting in high-frequency hearing loss. Cisplatin causes degeneration of hair cells (HCs) and spiral ganglion neurons (SGNs) in the inner ear, which are essential components of the hearing process and cannot be regenerated in mammals. As the affected cells primarily die by apoptosis, we tested several anti-apoptotic small molecules to protect these cells from drug-induced toxicity. We found that the general caspase inhibitor Emricasan could significantly counteract the toxic effects of cisplatin in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, phoenix auditory cells, and primary SGNs. Importantly, the anti-cytotoxic effect in neuronal cells was even more pronounced than the effect of sodium thiosulfate (STS), which is currently the only approved prevention option for cisplatin-induced ototoxicity. Finally, we tested the protective effect of Emricasan treatment in the context of another ototoxic drug, i.e., the aminoglycoside antibiotic neomycin, and again found a significant increase in cell viability when the cultures were co-treated with Emricasan. These results suggest a promising strategy to prevent ototoxicity in patients by temporarily blocking the apoptotic pathway when applying cisplatin or aminoglycoside antibiotics.Key messagesAnti-apoptotic small molecules can reduce cisplatin-induced toxicity.Emricasan can effectively exert its anti-apoptotic effect on cochlear cells.Strong protection from cisplatin- and neomycin-induced cytotoxicity with Emricasan.Sodium thiosulfate and Emricasan provide similar protective effects to cisplatin-treated cells.Emricasan is more potent than sodium thiosulfate in reducing neomycin-induced cytotoxicity.

Impairment of brain function in a mouse model of Alzheimer's disease during the pre-depositing phase: The role of α7 nicotinic acetylcholine receptors

Alzheimer’s disease (AD) is an age-dependent incurable neurodegenerative disorder accompanied by neuroinflammation, amyloid accumulation, and memory impairment. It begins decades before the first clinical symptoms appear, and identifying early biomarkers is key for developing disease-modifying therapies. We show now in a mouse model of AD that before any amyloid deposition the brains of 1.5-month-old mice contain increased levels of pro-inflammatory cytokines IL-1β and IL-6, decreased levels of nicotinic acetylcholine receptors (nAChRs) in the brain and brain mitochondria and increased amounts of α7 nAChR-bound Aβ1–42, along with impaired episodic memory and increased risk of apoptosis. Both acute (1-week-long) and chronic (4-month-long) treatments with α7-selective agonist PNU282987, starting at 1.5 months of age, were well tolerated. The acute treatment did not affect the levels of soluble Aβ1–42 but consistently upregulated the α7 nAChR expression, decreased the level of α7-Aβ1–42 complexes, and improved episodic memory of 1.5-month-old mice. The chronic treatment, covering the disease development phase, strongly upregulated the expression of all abundant brain nAChRs, reduced both free and α7-coupled Aβ1–42 within the brain, had anti-inflammatory and antiapoptotic effects, and potently upregulated cognition, thus identifying α7 nAChRs as both early biomarker and potent therapeutic target for fighting this devastating disease.

Effect on serum metabolomics of rats with premature ovarian insufficiency by Zhibian (BL54) through Shuidao (ST28) acupuncture.

To analyze the serum metabolic targets of the "Zhibian (BL54) through Shuidao (ST28)" acupuncture technique in cyclophosphamide (CTX)-induced premature ovarian insufficiency (POI) model rats and to elucidate the potential molecular mechanism of acupuncture in improving POI. We used an intraperitoneal injection of CTX to establish the POI rat model (POI group) and compared serum hormone levels and ovarian histopathological changes to evaluate the effect of the Zhibian (BL54) through Shuidao (ST28) technique (ZS + POI group) on ovarian function. Then, nontargeted metabolomics was performed using rat serum by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). After acupuncture intervention, the serum hormone levels and ovarian pathological morphology of POI rats were effectively improved. Moreover, UPLC-Q-TOF/MS results showed that the ZS + POI group showed a significant reversal of the levels of 6 differential metabolites. Among them, the levels of four serum metabolic markers, divanillyltetrahydrofuran ferulate, trans-ferulic acid, tryptamine, and neuraminic acid, increased significantly. Further analysis of biological effects showed that all metabolites were involved in the regulation of reproductive hormone levels and antioxidant and antiapoptotic effects. The "Zhibian (BL54) through Shuidao (ST28)" acupuncture method may improve the ovarian function of POI rats by regulating serum metabolite markers to exert antioxidant and antiapoptotic effects, which provides a theoretical basis for the clinical application of acupuncture in the treatment of POI.

Combining Network Pharmacology and Transcriptomics to Investigate the Mechanisms of Yujiang Paidu Decoction in the Treatment of Chronic Rhinosinusitis with Nasal Polyps.

Yujiang Paidu Decoction (YJPD)has demonstrated clinical efficacy in the treatment of chronic rhinosinusitis. However, the effects and mechanisms of the YJPD on chronic rhinosinusitis with nasal polyps (CRSwNP) remain unclear. This study aimed to elucidate thepotential mechanismofaction of YJPD inthetreatmentofCRSwNP based on networkpharmacology, transcriptomics and experiments. A CRSwNP mouse model was established using ovalbumin (OVA) and staphylococcus aureus enterotoxin B (SEB) for 12 weeks and the human nasal epithelial cell (HNEpC) model was induced with IL-13 in vitro. Behavioraltests, scanning electron microscopy (SEM), micro-CT and pathological change of nasal tissues were observed to investigate the therapeutic effects of YJPD. Network pharmacology and transcriptomics were launched to explore the pharmacological mechanisms of YJPD in CRSwNP treatment. Finally, an ELISA, immunofluorescence, RT-qPCR, Western blotting and Tunel were performed for validation. Different doses of YJPD intervention effectively alleviated rubbing and sneezing symptoms in CRSwNP mice. Additionally, YJPD significantly reduced abnormal serological markers, structural damage of the nasal mucosa, inflammatory cell infiltration, goblet cell increases, and inhibited OVA-specific IgE levels and the secretion of Th2 cytokines such as IL-4, IL-5, and IL-13. Moreover, transcriptomics and network pharmacology analyses indicated that YJPD may exert anti-inflammatory and anti-apoptotic effects by inhibiting the MAPK/AP-1 signaling pathway. The experimental findings supported this conclusion, which was further corroborated by similar results observed in IL13-induced HNEpCs in vitro. YJPD could alleviate inflammatory status and epithelial apoptosis by inhibiting aberrant activation of MAPK/AP-1 signaling pathway. This finding provides a strong basis for using YJPD as a potential treatment in CRSwNP.

Treatment of erectile dysfunction by intracavernosal administration of mesenchymal stem cells in patients with diabetes mellitus.

The purpose of study is to assess and analyse the effectiveness of their use in the treatment of erectile dysfunction in patients with diabetes mellitus. The literature search was conducted using systematic methods and analysis in databases such as Web of Science, Scopus, PubMed, Elsevier, and Springer, with 41 sources included for further review. The study highlights microangiopathic and neuropathic links as key factors in erectile dysfunction development in diabetic patients, stemming from endothelial dysfunction and conductivity disturbances. Mesenchymal stem cell therapy from bone marrow, adipose tissue, and umbilical cord mitigates pathogenic impact through regenerative and anti-apoptotic effects. Due to this, most studies indicate high efficacy of the treatment and rapid therapeutic action through intracavernosal administration. Some studies suggest an increase in the body's receptor sensitivity to other drugs, such as sildenafil. From the perspective of further research on this issue, standardising the preparation of stem cells and the treatment method using a large sample size is essential to introduce such a method as an extremely promising therapy for this delicate issue in men into practical medicine. The practical value of the study lies in the systematisation of information on different sources of mesenchymal stem cells for treating erectile dysfunction.

Sodium Tanshinone IIA Sulfonate Protects Primary Cardiomyocytes Against Radiation-Induced Myocardial Injury via the p38 Pathway.

Sodium tanshinone IIA sulfonate (STS), which is extracted from a Chinese medicinal herb, possesses many pharmacologic functions, such as coronary dilation, anti-inflammatory properties, and antiapoptotic and antioxidant effects. It remains unknown whether STS can protect cardiomyocytes injured after radiation therapy. An in vitro Sprague-Dawley (SD) rat neonatal cardiomyocyte system was established. Primary cardiomyocytes (PCMs) from neonatal SD rats were isolated under sterile conditions. PCM cells were divided into a control group (0 Gy/hour) and 5 experimental radiation therapy groups (0.25 Gy/hour, 0.5 Gy/hour, 1 Gy/hour, 2 Gy/hour, and 4 Gy/hour). Cell viability, the content of malondialdehyde (MDA), the lactate dehydrogenase (LDH) leakage rate, and superoxide dismutase (SOD) and glutathione (GSH) activities were recorded separately in each group after 7 days of culture. Western blot was used to detect the levels of p38, caspase-3 protein, and X protein (BAX) associated with B-cell lymphoma 2 (Bcl-2) in PCMs. X-rays inhibited cell growth, decreased cell viability, and induced an oxidative stress response in PCMs. STS and SB203580 (the inhibitor of P38 mitogen-activated protein kinase pathway) alleviated X-ray-induced damage to PCMs. An enzyme-linked immunosorbent assay showed that X-rays increased the cTnT level. STS and SB203580 ameliorated the X-ray-induced increase in cTnT leakage. X-rays enhanced the expression of p38/p-p38 and caspase-3 while reducing the expression of Bcl-2/BAX in PCMs, as demonstrated by western blotting. STS and SB203580 mitigated the changes in protein expression triggered by X-ray radiation. In conclusions, STS was shown to exert significant cardioprotective, anti-inflammatory, and antioxidant effects in PCMs by inhibiting the p38 mitogen-activated protein kinase pathway.

Screening Targets and Therapeutic Drugs for Alzheimer's Disease Based on Deep Learning Model and Molecular Docking.

Alzheimer's disease (AD) is a neurodegenerative disorder caused by a complex interplay of various factors. However, a satisfactory cure for AD remains elusive. Pharmacological interventions based on drug targets are considered the most cost-effective therapeutic strategy. Therefore, it is paramount to search potential drug targets and drugs for AD. We aimed to provide novel targets and drugs for the treatment of AD employing transcriptomic data of AD and normal control brain tissues from a new perspective. Our study combined the use of a multi-layer perceptron (MLP) with differential expression analysis, variance assessment and molecular docking to screen targets and drugs for AD. We identified the seven differentially expressed genes (DEGs) with the most significant variation (ANKRD39, CPLX1, FABP3, GABBR2, GNG3, PPM1E, and WDR49) in transcriptomic data from AD brain. A newly built MLP was used to confirm the association between the seven DEGs and AD, establishing these DEGs as potential drug targets. Drug databases and molecular docking results indicated that arbaclofen, baclofen, clozapine, arbaclofen placarbil, BML-259, BRD-K72883421, and YC-1 had high affinity for GABBR2, and FABP3 bound with oleic, palmitic, and stearic acids. Arbaclofen and YC-1 activated GABAB receptor through PI3K/AKT and PKA/CREB pathways, respectively, thereby promoting neuronal anti-apoptotic effect and inhibiting p-tau and Aβ formation. This study provided a new strategy for the identification of targets and drugs for the treatment of AD using deep learning. Seven therapeutic targets and ten drugs were selected by using this method, providing new insight for AD treatment.

The Role of Erythropoietin in Bovine Sperm Physiology.

Erythropoietin (EPO), a hormone secreted mainly by the kidney, exerts its biological function by binding to its cell-surface receptor (EpoR). The presence of EPO and EpoR in the male and female reproductive system has been verified. Therefore, some of the key properties of EPO, such as its antioxidant and antiapoptotic effects, could improve the fertilizing capacity of spermatozoa. In the present study, the effect of two different concentrations of EPO (10 mIU/μL and 100 mIU/μL) on bovine sperm-quality parameters was evaluated during a post-thawing 4-h incubation at 37 °C. EPO had a positive effect on sperm motility, viability, and total antioxidant capacity. Moreover, EPO inhibited apoptosis, as it reduced both BCL2-associated X apoptosis regulator (Bax)/B-cell lymphoma 2 (Bcl-2) ratio and cleaved cysteine-aspartic proteases (caspases) substrate levels in a dose-dependent manner. In addition, EPO induced sperm capacitation and acrosome reaction in spermatozoa incubated in capacitation conditioned medeia. These results establish a foundation for the physiological role of EPO in reproductive processes and hopefully will provide an incentive for further research in order to fully decipher the role of EPO in sperm physiology and reproduction.