Journal of Physiology and Pharmacology最新文献

{"title":"Effect of short-term of vaginal therapy with prasterone before urogynecological surgery in woman.","authors":"K Tomczyk, M Kampioni, M Muszynska, P Piekarski, M Wilczak, K Chmaj-Wierzchowska","doi":"10.26402/jpp.2026.2.09","DOIUrl":"10.26402/jpp.2026.2.09","url":null,"abstract":"<p><p>Among many different types of vaginal therapy for women suffering from urogynecological disorders, we may distinguish hormonal vaginal treatment with oestrogens. Lately, there has been a new option of treatment- prasterone. It is prohormone which can be further metabolized and acts like both estrogens and androgens. The purpose of the study is to analyze the effect of short-term vaginal application of prasterone. We checked 39 women of age 28-85 suffering from prolapse or stress incontinence that consented to surgical treatment and hadn't used vaginal estrogens before. We analyzed vaginal maturation index (VMI), biocenosis, endometrial thickness, and blood level of estradiol and dehydroepiandrosterone sulfate (DHEA-S) The analyses were performed before and after eight weeks of vaginal preparation with prasterone 6.5 mg once daily, administered intravginally. Results of the main variables before and after treatment were as follows: estradiol [pg/mL] 63.25±101.85 vs. 49.62±99.85 (p=0.94); DHEA-S [µmol/L] 3.93±2.19 vs. 4.28±2.55 (p=0.02); endometrial thickness [mm] 3.65±3.79 vs. 3.97±3.42 (p=0.97); biocenosis score [1-4] 2.95±0.94 vs. 2.50±0.76 (p=0.02). The study showed a significant increase in the DHEA-S levels after treatment and decrease in the degree of biocenosis. No substantial differences were found in relation to estradiol levels, or endometrium size. Moreover, a notable increase in the VMI was observed. Prasterone preparation has the effect of improving vaginal maturation and bacterial flora in both patients with stress urinary incontinence and female organ prolapse. In addition, these parameters are improved in both reproductive and menopausal women.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 2","pages":"279-287"},"PeriodicalIF":1.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148220628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesity-associated carcinogenesis with treatment gaps: A narrative review of updated evidence and natural products strategies.","authors":"M J S Mantargi, S S Alavudeen, V Easwaran, N Goruntla, M Afzal, N A Khan, A T M Hussein, A A S Mohammad","doi":"10.26402/jpp.2026.2.01","DOIUrl":"10.26402/jpp.2026.2.01","url":null,"abstract":"<p><p>Obesity contributes significantly to cancer development due to superfluous adipose tissue interfering with physiologic balance. The current narrative review outlines the molecular and physiological pathways linking obesity and cancer and highlights the role of natural products as preventive and therapeutic agents. Underlying processes intertwining obesity and cancer include chronic low-grade inflammation, insulin resistance, hormonal imbalance, adipokine dysregulation, oxidative stress, and changes in the gut microbiome. All of these are used to facilitate tumor-promoting microblood to increase tumor growth and help cancerous cells proliferate and metastasize. There are specific mediators that are important in the activation of oncogenic signalling pathways, such as tumor necrosis factor-alpha, interleukin 6, insulin-like growth factor-1, estrogen, leptin, and reactive oxygen species. Phytochemicals that have the potential to be used as natural anti-inflammatory, antioxidant, and anticancer agents include, but are not limited to, curcumin, resveratrol, epigallocatechin gallate (EGCG), quercetin, berberine, gingerol, and capsaicin. The compounds regulate major molecular pathways of the obesity-related cancers. A new method of delivery that automatically and involuntarily targets the delivery mechanism by use of nanotechnologies has demonstrated its capacity in increasing bioavailability and therapeutic effects of these bioactive agents. To reduce the burden of this impact of obesity on cancers, a strategy involving a blend of lifestyle changes, pharmacological treatment, and science-based natural solutions is required. We conclude that in order to increase the potential of natural products, there is a need to have clinical studies on oncology and public health, as well as regulatory advancement.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 2","pages":"143-154"},"PeriodicalIF":1.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148220546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of the KEAP1/NRF2 pathway by claudin-2-targeted lymphoid enhancer-binding factor 1 binding in gastric cancer progression.","authors":"J Yao, Y H Zhang, Y X Ling, X Shi","doi":"10.26402/jpp.2026.2.06","DOIUrl":"10.26402/jpp.2026.2.06","url":null,"abstract":"<p><p>This research aimed to examine the clinical relevance and biological function of the tight junction protein claudin-2 (CLDN2) in gastric cancer, along with its regulatory interactions with lymphoid enhancer-binding factor 1 (LEF1) and the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway. Analysis of CLDN2 expression and its prognostic implications in gastric cancer was conducted using data from the Cancer Genome Atlas (TCGA) database. The effects of CLDN2 or LEF1 on gastric cancer (GC) cells were detected by RT-qPCR, Western blot, cell-counting kit-8 (CCK-8), transwell assay, flow cytometry, CO-IP and immunofluorescence assays. The interactions between CLDN2 and LEF1 was predicted and validated using Gene MANIA and GEPIA. The functional association between CLDN2 and LEF1 was analyzed by rescue experiments. In GC tissues, CLDN2 was significantly upregulated and correlated with tumor stage, lymph node metastasis, and poor prognosis, showing elevated levels in young patients (21-40 years old) and individuals infected with Helicobater pylori (H. pylori). CLDN2 silencing inhibited GC cell proliferation, migration and invasion, induced G1-phase cycle block and apoptosis, and decreased cyclin D1 expression. CLDN2 and LEF1 were positively correlated and directly interacted, and suppressing LEF1 hindered the progression of GC. CLDN2 reduced KEAP1 expression and promoted NRF2 protein stability through post-transcriptional regulation. Silencing CLDN2 or LEF1 activated the KEAP1/NRF2 pathway and inhibited downstream p65, IkappaB kinase (IKK) and IκB protein expression. Reducing LEF1 levels counteracted the effects of CLDN2 on GC cell growth and KEAP1/NRF2 pathway. Increased levels of CLDN2, which modulate the LEF1 and KEAP1/NRF2 pathways, are correlated with GC progression and may be used as a marker for poor prognosis.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 2","pages":"233-248"},"PeriodicalIF":1.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148220607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mulberry leaf supplementation improves glycemic control but not renal or cardiovascular markers in spontaneously hypertensive rats.","authors":"A Gryn-Rynko, P Muszynski, M A Janiak, R Amarowicz, A Chrustek, M S Majewski","doi":"10.26402/jpp.2026.2.05","DOIUrl":"10.26402/jpp.2026.2.05","url":null,"abstract":"<p><p>White mulberry (Morus alba L.) leaves have traditionally been used to improve glycemic control in diabetic and prediabetic individuals; however, their effects in hypertension remain insufficiently characterized. This study evaluated the impact of dietary mulberry leaf supplementation on blood biochemical parameters and on renal, cardiac, and vascular outcomes in spontaneously hypertensive rats (SHR). In addition, the content of the key bioactive compound 1-deoxynojirimycin (DNJ) was quantified. Male SHRs, aged 4 months (n=10 per group), were assigned to receive either standard rat chow or chow supplemented with ground mulberry leaves (7% w/w; ~4.0 g/kg body weight; 1.46±0.07 mg DNJ/rat/day) for eight weeks. Mulberry leaves contained 1.15±0.01 mg DNJ/g dry weight, as determined by RP-HPLC-DAD. Supplementation significantly reduced glycated hemoglobin (HbA1c: 2.23% vs. 1.98%, p=0.021) and attenuated postprandial glucose elevation during oral glucose tolerance testing (112 vs. 94 mg/dL at 120 min, 0.85-fold; p=0.005). No significant effects were observed on renal, cardiac, or vascular biomarkers, as assessed by ELISA and standard blood analyses. Kidney histology, including vascular thickness and density, was unchanged. Vascular reactivity to acetylcholine and noradrenaline did not differ between groups, and no differences were detected in the isolated perfused heart model. These findings suggest a potential role for Morus alba leaves in dietary strategies targeting glucose regulation in hypertension and underscore the need for longer-term and translational investigations.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 2","pages":"219-232"},"PeriodicalIF":1.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148220543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Danggui Shaoyao San alleviates nephrotic syndrome by regulating inerleukin 13/signal transducer and activator of transcription 6 axis.","authors":"T Z Zhang, M Qin","doi":"10.26402/jpp.2026.2.10","DOIUrl":"10.26402/jpp.2026.2.10","url":null,"abstract":"<p><p>The research focused on investigating the function and underlying mechanisms of Danggui Shaoyao San (DSS) in nephrotic syndrome (NS). The NS rat model was established using doxorubicin (Dox), and 24-hour urinary protein (UP) level was measured in NS rats. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were detected using an automatic biochemical analyzer; morphological changes of renal tissues were observed by HE staining; serum interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) levels were measured by ELISA; and the protein expression of interleukin 13 (IL-13), signal transducer and activator of transcription 6 (STAT6), phospho signal transducer and activator of transcription 6 (p-STAT6) was evaluated by Western blot. NS cell model was established using Dox. Cell viability was detected by MTT, and apoptosis was detected by flow cytometry. DSS reduced UP, BUN, and SCr levels and also decreased serum IL-6, IL-1β, and TNF-α levels in NS rats in a dose-dependent manner. Renal tissue injury in NS rats was significantly lessened by DSS. Finally, DSS increased cell viability and decreased apoptosis. In a dose-dependent manner, DSS led to a dose-dependent inhibition of IL-13 and p-STAT6 protein expression. DSS alleviates NS by inhibiting IL-13/STAT6 axis activation.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 2","pages":"289-296"},"PeriodicalIF":1.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148220565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aldosterone, not only an adrenal mineralocorticoid: An updated review of its functions, mechanisms, biosynthesis, hormone system and regulation in multiple organs and tissues.","authors":"Z Pang, H Vapaatalo, R Korpela","doi":"10.26402/jpp.2026.2.02","DOIUrl":"10.26402/jpp.2026.2.02","url":null,"abstract":"<p><p>Aldosterone, the principal mineralocorticoid, is critical for regulating electrolyte balance and blood pressure through its interaction with mineralocorticoid receptor (MR). This review traces the historical evolution of aldosterone research, from its discovery in the 1950s to current insights into its biosynthesis and signaling mechanisms. It details the enzymatic pathways of aldosterone production, emphasizing the role of cytochrome P450 11β2 (CYP11B2) in both adrenal and extra-adrenal tissues, and elucidates the structural basis for its specificity. The physiological roles of aldosterone are explored, highlighting its regulation of ion transport proteins and its impact on cardiovascular health, including vascular remodeling and myocardial fibrosis. The review examines the complex signaling pathways activated by aldosterone, encompassing MR-dependent genomic and non-genomic effects, as well as MR-independent mechanisms. It also addresses aldosterone-independent MR activation by glucocorticoids under conditions of reduced 11β hydroxysteroid dehydrogenase type 2 (11β-HSD2) expression. Furthermore, the review consolidates findings on regulatory factors influencing aldosterone synthesis, such as the renin-angiotensin-aldosterone system, adrenocorticotropic hormone, potassium, sodium, and glucose levels, emphasizing systemic and local regulation, as a foundation for future clinical interventions in disorders associated with dysregulated aldosterone signaling.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 2","pages":"155-184"},"PeriodicalIF":1.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148220585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6-gingerol alleviates Alzheimer's disease in rats through the Pumilio RNA binding family member 1/microRNA-340-5p/pleomorphic adenoma gene like-2/estimated glomerular filtration rate/hypoxia-inducible factor-1alpha/2alpha pathway.","authors":"F Guo, Y G Yang, S Q Sun, Y J Liu, W L Zhang, F Xin","doi":"10.26402/jpp.2026.2.04","DOIUrl":"10.26402/jpp.2026.2.04","url":null,"abstract":"<p><p>This study explores the modulatory role of Pumilio RNA-binding family member 1 (circ_PUM1) in the neuroprotective mechanisms of 6-gingerol against Alzheimer's disease (AD)-related neuronal injury, providing new insights into circRNA-mediated regulation of neurodegeneration. Variations in circRNA expression indirectly influenced by 6-gingerol (6-GIN) were comprehensively assessed within AD experimental frameworks. The AD phenotype was not absent when hippocampal amyloid-β (Aβ) was introduced into rats, nor when SK-N-SH and SK-SY5Y cells were subjected to Aβ challenge, jointly constructing complementary in vivo and in vitro paradigms for mechanistic exploration. Hippocampal injury was assessed by water content measurement, histological analysis, and TUNEL staining for apoptosis. In cell models, viability, apoptosis, and inflammatory cytokines (interleukin-6, inducible nitric oxide synthase, tumor necrosis factor-α) were quantified. The expression and localization of circ_PUM1 were examined, and its direct interaction with miR-340-5p was confirmed, revealing a regulatory axis potentially mediating the neuroprotective effects of 6-GIN. We found that administration of 6-GIN effectively counteracted Aβ1-42-induced neurotoxicity by alleviating neuronal apoptosis, oxidative injury, and inflammatory responses. These protective effects were evidenced by the reduction of neuronal damage and brain edema scores, decreased secretion of proinflammatory cytokines and lipid peroxidation products malondialdehyde (MDA), as well as the restoration of endogenous antioxidant enzymes such as superoxide dismutase and glutathione peroxidase. Exposure to aβ resulted in a marked downregulation of circ_pum1 expression accompanied by elevated miR-340-5p levels; notably, 6-GIN administration reversed these molecular alterations. Mechanistic analyses further confirmed that miR-340-5p directly binds to the 3'-UTR of pleomorphic adenoma gene like-2 (PLAGL2), thereby regulating the estimated glomerular filtration rate (EGFR)/hypoxia-inducible factor-1α (HIF-1α)/hypoxia-inducible factor-2α (HIF-2α) signaling axis implicated in neuronal survival and metabolic adaptation. Collectively, these findings suggest that circ_PUM1 confers neuroprotection against Alzheimer's disease pathology by sequestering miR-340-5p and activating the PLAGL2/EGFR/HIF-1α-HIF-2α cascade, elucidating a critical pathway through which 6-GIN exerts its therapeutic potential in attenuating Aβ-associated neuronal degeneration. In conclusion: 6-GIN alleviates Aβ-induced apoptosis, oxidative stress, and neuroinflammation in AD through circ_PUM1/miR-340-5p/PLAGL2/EGFR-HIF1/2A signaling pathway.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 2","pages":"197-217"},"PeriodicalIF":1.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148220540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of angiogenic factors in physiological pregnancy and pregnancy disorders - A review of the literature.","authors":"A Paluszkiewicz-Kwarcinska, E Wender-Ozegowska, J Kornacki, R Iciek, D Boron, A Swietlicki","doi":"10.26402/jpp.2026.2.03","DOIUrl":"10.26402/jpp.2026.2.03","url":null,"abstract":"<p><p>Proper placental angiogenesis is essential for fetal growth and maternal well-being during pregnancy. Imbalance between pro-angiogenic (placental growth factor (PlGF), vascular endothelial growth factor-A (VEGF-A)) and anti-angiogenic (soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng)) factors underlies preeclampsia (PE), fetal growth restriction (FGR), and related complications. The primary scientific aim of this review is to comprehensively synthesize current evidence on the physiological mechanisms of placental angiogenesis, with a focus on VEGF/PlGF and endothelial nitric oxide synthase-nitric oxide (eNOS-NO) pathways, and to evaluate the diagnostic and predictive utility of the sFlt-1/PlGF ratio in placenta-related disorders (PE, FGR, intrauterine fetal demise, preterm birth). A secondary aim is to assess the clinical integration of angiogenic biomarkers into risk stratification and management algorithms according to international guidelines. Narrative review of literature from PubMed, Scopus, and Web of Science (2015-2025). Search terms: \"placental angiogenesis\", \"VEGF\", \"PlGF\", \"sFlt-1\", \"sFlt-1/PlGF ratio\", \"preeclampsia\", \"fetal growth restriction\", \"spiral artery remodeling\", \"endothelial dysfunction\". Key references were PROGNOSIS study (64) and two-stage model (2) and VEGF pathway (13). In normal pregnancy, PlGF enhances VEGF-A signaling via VEGFR-1, promoting spiral artery remodeling and villous angiogenesis. In PE and FGR, placental hypoxia drives sFlt-1 overexpression, reducing free PlGF and VEGF, leading to endothelial dysfunction. The sFlt-1/PlGF ratio<38 rules out PE within 1 week (negative predictive value [NPV] 99.3%); ratios≥85 (early-onset) and≥110 (late-onset)), predict adverse outcomes with high specificity. First-trimester screening combining PlGF with maternal factors and uterine artery Doppler detects 90% of preterm PE cases. The sFlt-1/PlGF ratio is a robust biomarker for early detection and risk stratification of PE and FGR. Repeat testing improves individualized management. Integration into clinical practice, per International Society for the Study of Hypertension in Pregnancy (ISSHP) 2021 and American College of Obstetricians and Gynecologists (ACOG) 2023 guidelines, supports timely intervention and reduces perinatal morbidity.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 2","pages":"185-195"},"PeriodicalIF":1.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148220668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parthenolide ameliorates metabolic dysfunction-associated steatohepatitis by inhibiting M1 polarization by suppressing the nuclear factor-κB pathway.","authors":"D L Jiang, G W Liu, Q Y Zhang","doi":"10.26402/jpp.2026.2.08","DOIUrl":"10.26402/jpp.2026.2.08","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH) is an inflammatory disorder that results in ongoing liver inflammation and injury. During the course of hepatitis, parthenolide (PAR) promotes the recovery of liver function. Using a mouse model of MASH, the present study aimed to assess the effect of PAR on the condition. The MASH mouse model was developed using a high-fat diet combined with high-carbohydrate drinking, and measurements were taken for body weight, liver-to-body mass ratio, non-alcoholic fatty liver disease activity score, and levels of alanine aminotransferase and aspartate aminotransferase. Subsequently, liver injury was detected using hematoxyling and eosin staining, hepatic lipid accumulation was evaluated with oil red O staining, and liver fibrosis was assessed through Masson staining. Macrophage infiltration and M1 polarization were assessed by immunofluorescence staining for F4/80; and lipid metabolic, fibrotic, and pro-inflammatory indicators were detected by RT-qPCR; nuclear factor-κB (NF-κB) signaling pathway was assessed by Western blot. We found that PAR alleviated liver injury, improved lipid metabolism, and reduced fibrosis in MASH mice,. It also lowered macrophage infiltration in the liver, particularly decreasing M1 macrophages and pro-inflammatory cytokines. PAR inhibited the activation of the NF-κB pathway, and the protective effects were attenuated by an NF-κB pathway activators. We conclude that PAR ameliorates liver injury, hepatic lipid metabolism, fibrosis and inflammation in MASH mice, likely by suppressing the NF-κB pathway and thereby inhibiting M1 polarization.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 2","pages":"265-277"},"PeriodicalIF":1.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148220590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutamyl-tRNA synthetase 2 regulates mitochondrial biogenesis and reactive oxygen species homeostasis mediatingenzalutamide resistance by targeting striatin 4 in prostate cancer cells.","authors":"B Q Wang, X Wang, W Liu, L Jin","doi":"10.26402/jpp.2026.2.07","DOIUrl":"https://doi.org/10.26402/jpp.2026.2.07","url":null,"abstract":"<p><p>Although enzalutamide (ENZA) has improved the overall survival of patients with metastatic prostate cancer, ENZA resistance (ENZA-resistant) inevitably develops, largely limiting its efficacy. Alternative oncogenic pathways may bypass androgen receptor (AR) signaling to promote ENZA-resistant. Glutamyl-tRNA synthetase 2 (EARS2) is involved in mitochondrial biogenesis and is associated with cancer, but its action mechanism in prostate cancer (PCa) is not well defined. EARS2 expression was detected in primary PCa and castrate-resistant prostate cancer samples, ENZA-resistant cell lines, and ENZA-resistant xenograft models, and the prognostic relationship of EARS2 in patients with PCa was analyzed. In AR-sensitive LNCaP cells, changes in EARS2 expression were explored before and after stimulation with dihydrotestosterone (DHT) or bicalutamide. AR was knocked down in AR-positive LNCaP and C4-2B cells to explore the relationship between EARS2 and AR. The effect of EARS2 on PCa cells was further explored. ENZA-resistant xenograft model was built to explore the effect of EARS2 on tumorigenesis in vivo. EARS2 was knocked down in C4-2B-ENZA-resistant, and the relationship between EARS2 and mitochondrial biogenesis and reactive oxygen species (ROS) homeostasis was investigated in PCa cells. Finally, the relationship between EARS2 and striatin 4 (STRN4) was explored. EARS2 expression was elevated in PCa and correlated with ENZA-resistant, and high EARS2 expression was associated with poorer patient prognosis. In androgen-sensitive LNCaP cells, DHT inhibited EARS2 expression, and silencing AR increased EARS2 expression. Suppressing EARS2 inhibited the proliferation, colony formation, migration and invasion ability, down-regulated the IC50 of ENZA in ENZA-resistant cells, and promoted apoptosis. Stable EARS2 downregulation in C4-2B-ENZA-resistant significantly inhibited tumor growth. Suppressing EARS2 in ENZA-resistant cells may lead to increased mitochondrial biogenesis and ROS generation. Mechanistically, EARS2 inhibited mitochondrial biogenesis and ROS generation in PCa cells by targeting STRN4. EARS2 targets STRN4 to modulate mitochondrial biogenesis and ROS homeostasis mediating ENZA-resistant.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 2","pages":"249-264"},"PeriodicalIF":1.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148220617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}