Journal of Molecular Histology最新文献

Diabetes mellitus is associated with decline in cognitive function and changes in brain structure. Statins have received increasing attention to be used as neuroprotective drug. We examined the neuroprotective effects of atorvastatin on neuropathological alterations such as learning and memory performance, the amyloid-β formation, and expression of nitric oxide synthases (NOSs) in hippocampus of streptozotocin (STZ)-induced diabetic rats. Adult male Wistar rats were divided into four groups; The normal control group, STZ-induced diabetes group, STZ-induced diabetic rats followed by treatment with atorvastatin group and normal rats treated with atorvastatin. The passive avoidance test was used to evaluate the learning and memory status of animals. Blood and hippocampus samples were obtained for biochemical and histological analysis. The expressions of nitric oxide synthases were immunohistochemically detected, and histopathological changes of amyloid beta were examined using Congo red stain in CA1 region of hippocampus. Count of congo red positive cells in CA1 region increased in diabetic rats, however atorvastatin treatment decreased it. Amyloid-β levels and S100B levels in the hippocampus and plasma increased in diabetic rats, atorvastatin treatment decreased. Total nitrite-nitrate levels increased, while iNOS expression decreased in the CA1 area of hippocampus in atorvastatin treated diabetic rats, eNOS and nNOS expression increased. The retention latency times of diabetes group decreased, however atorvastatin treatment to diabetic rats prolonged at the 48th hour and 72nd hour. Atorvastatin improved the long-term memory by suppressing the formation of amyloid-β, increasing eNOS and nNOS protecting the blood brain barrier in diabetic rats.

Pre-eclampsia (PE) is a common pregnancy complication, closely associated with endothelial dysfunction and inhibition of angiogenesis. This study aims to explore the pathological mechanisms causing endothelial dysfunction and suppressed angiogenesis in PE, with the aim of identifying potential drug targets. Human umbilical vein endothelial cells (HUVECs) were exposed to angiotensin II (Ang-II) to mimic PE-related endothelial dysfunction. Angiogenic capacity was evaluated using tube formation assay, scratch assay, flow cytometry, and CCK-8 assay. A Reduced Uterine Perfusion Pressure (RUPP) mouse model was established to recapitulate PE. Expression profiles of hypoxia-inducible factor-1α (HIF-1α), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sENG), and tumor necrosis factor-α (TNF-α) were quantified via Western blot and RT-qPCR. Biochemical assessments included levels of malondialdehyde, superoxide dismutase, glutathione, and the urine protein/creatinine (UP/cr) ratio. Systolic blood pressure was measured while placental histopathology was examined using hematoxylin and eosin (HE) staining. In HUVECs exhibiting endothelial dysfunction, ICAM-1 and VCAM-1 were markedly upregulated, whereas HIF-1α expression was significantly reduced. Overexpression of HIF-1α boosted HUVEC proliferation and migration, attenuated apoptosis and oxidative stress, enhanced expression of VEGF and PlGF, and suppressed expression of sFlt-1, sENG, and TNF-α, thereby promoting angiogenesis. In the RUPP-modeled PE mouse model, diminished HIF-1α expression coincided with elevated ICAM-1 and VCAM-1, leading to endothelial dysfunction, elevated systolic blood pressure, and increased UP/cr ratio. Conversely, HIF-1α overexpression ameliorated placental tissue damage and oxidative stress, upregulated VEGF and PlGF, downregulated sFlt-1, sENG, TNF-α, ICAM-1, and VCAM-1, and restored angiogenic capacity. HIF-1α ameliorates endothelial dysfunction in PE by suppressing the sFlt-1/sENG/TNF-α signaling pathway, thereby promoting angiogenesis and alleviating PE.

Huangqi Guizhi Wuwu Decoction (HGWD) has shown laboratory efficacy in autoimmune diseases, however its effectiveness and mechanism in addressing the decline of immune function remain unclear. We first established a cyclophosphamide-induced mouse model of immunosuppression and evaluated various immune indicators to determine the efficacy of HGWD in improving the immune function of CTX-immunosuppressed mice. Next, we conducted serum non-targeted metabolomics analysis to investigate HGWD’s effects on serum differential metabolites and used KEGG pathway enrichment analysis to identify the key pathways through which HGWD improves immune function. Finally, we validated HGWD’s impact on arachidonic acid (AA) metabolism and ferroptosis. HGWD treatment significantly improves the number of immune cells, ameliorates thymus and spleen tissue pathology, and restores the immune function. Non-targeted metabolomics analysis indicated that AA metabolism was a common pathway among the control group, CTX group, and H-HGWD group. HGWD intervention resulted in downregulation of serum levels of 15(S)-HpETE, 16(R)-HETE, Prostaglandin H2, and Prostaglandin G2 in CTX-immunosuppressed mice, while upregulating the level of 12(S)-HETE. RT-qPCR and Western blot analyses revealed that HGWD intervention significantly downregulated the expressions of ALOX15, CYP2C, ALOX12, and COX1, while upregulating GPX4 expression. Furthermore, HGWD intervention reduced TUNEL-positive expression in spleen tissue, improved levels of ferroptosis-related factors (total iron, MDA, 4-HNE, GSH/GSSG), and modulated expressions of ferroptosis-related proteins (FTL, FTH, TRF, and ACSL4). Our research has confirmed the significant potential of HGWD in improving the immune function of CTX-immunosuppressed mice. Specifically, HGWD may improve immune function by regulating AA metabolism to inhibit ferroptosis.

17α-Ethinylestradiol (EE2) is a synthetic estrogen derived from 17β-estradiol and widely used in oral contraceptives. It interferes with the endocrine system and disrupts hormonal balance. This study investigated the long-term effects of prenatal and pubertal EE2 exposure on the dorsal prostate of aging gerbils. Adult female gerbils (90–120 days old) received EE2 (15 µg/kg/day) and were assigned to three groups (n = 5): Control (untreated), EE2/PRE (exposed during gestational days 18–22), and EE2/PUB (exposed during postnatal days 42–49). After 12 months, the animals were euthanized, and dorsal prostates were collected for biometric, histopathological (including quantification of prostatic acini/section and lesion multiplicity), and Morphometric analyses (epithelial height and muscle thickness), with stereological evaluation of the epithelium, lumen, muscle, stroma, blood vessels, and collagen fibers. Tissue sections were stained with Hematoxylin–Eosin, Gömori’s Trichrome, and Picrosirius Red. Results showed increased muscular thickness and decreased vascular volume in the EE2/PRE group, while the EE2/PUB group exhibited reduced volumes of the epithelium, lumen, and collagen fibers. Lesion analysis revealed a reduction in prostatic intraepithelial neoplasia (PIN) and an increase in luminal inflammation in the EE2/PUB group. These findings indicate that the biological effects of EE2 vary according to the timing of exposure, with both prenatal and pubertal periods representing critical developmental windows. EE2 exposure during these stages can induce alterations in epithelial-stromal interactions in a lobe-specific manner. Hormonal imbalance triggered ERα/ERβ signaling, influencing cellular differentiation and promoting inflammation. These distinct outcomes highlight how endocrine-disrupting chemicals (EDCs) compromise prostate homeostasis through hormone reprogramming and receptor-mediated pathways.

Aplastic anemia, a prevalent disorder of the hematopoietic system, may develop as a result of bone marrow suppression induced by chemotherapeutic agents. Given its iatrogenic nature, the identification of affordable and effective therapeutic interventions remains a clinical priority. Angelica sinensis Radix (ASR) has been widely utilized in traditional Chinese medicine for anemia management and is supported by extensive clinical application. The aim of the present study is to examine the physicochemical characteristics of A. sinensis Radix-derived carbon dots (ASR-CDs) and to evaluate their therapeutic effects on hematopoietic injury in murine models exposed to chemotherapeutic agents. ASR-CDs were synthesized via calcination of ASR. The resulting nanomaterials were characterized in terms of particle morphology and surface functional groups. A Cell Counting Kit-8 (CCK-8) assay was used to assess biocompatibility. A zebrafish anemia model was employed to compare the anti-anemic efficacy of ASR-CDs with that of other therapeutic agents. A murine model of hematopoietic injury was established using cyclophosphamide and busulfan to investigate the effects of ASR-CDs on hematopoietic function. ASR-CDs displayed a nanoscale particle size range (1.444–4.006 nm) and surface groups including amino, carboxyl, and hydroxyl functionalities. Cellular assays involving RAW264.7 cells indicated no cytotoxicity, indicating favorable biosafety. In the zebrafish anemia model, ASR-CDs demonstrated superior efficacy in alleviating anemia compared to other tested agents. In mice, ASR-CDs significantly diminished chemotherapy-induced reduction in body weight, immune organ indices (liver, spleen, thymus), and peripheral blood cell counts (white blood cells, red blood cells, and platelets). Furthermore, ASR-CDs modulated hematopoiesis-related serum factors, with higher dosages producing more pronounced regulatory effects. ASR-CDs exerted a beneficial effect on chemotherapy-induced anemia. These results support the therapeutic potential of herbal-derived carbon dots and highlight the applicability of nanomaterials in pharmaceutical development.

The long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR), a tumor suppressor associated with various human cancers, regulates multiple cellular processes. However, the role of HOTAIR in papillary thyroid carcinoma remains unclear. Therefore, the purpose of the present study was to investigate the effect of HOTAIR on the proliferation and migration of PTC cells, and to explore its possible mechanism. The initial step involves conducting an analysis in The Cancer Genome Atlas database of the HOTAIR expression level between PTC and normal tissue samples. Reverse transcription-quantitative PCR was conducted to detect HOTAIR and microRNA (miRNA, miR)-206 expression in each cell line. We assessed cell proliferation using the CCK-8 and MTT assays. We employed the wound-healing and transwell assays to evaluate cell migration. The HOTAIR/miR-206/c-Met targeting relations were verified through dual-luciferase reporter assay. We analyzed changes in protein expression downstream of the c-Met/AKT/mTOR pathway by Western blotting. Our results showed that HOTAIR was highly expressed in PTC cells. Silencing HOTAIR significantly inhibited the proliferation and migration of PTC cells. Conversely, miR-206 expression was downregulated in PTC cells. Importantly, overexpressing miR-206 significantly inhibited PTC cell proliferation and migration. In conclusion, HOTAIR acts as a sponge for miR-206, thereby alleviating its repression of c-Met and activating the AKT/mTOR signaling pathway in PTC cells.

Cardiovascular diseases represent one of the most serious health issues, accounting for worldwide morbidity and mortality. Doxorubicin (DOX) induces cardiotoxicity through the formation of free radicals. Stem cell therapy appears to be a promising alternative to existing treatments for myocardial injury, as it can produce growth factors and cytokines that are involved in wound healing. Besides its orexigenic properties, ghrelin was proven to have a cardiovascular protective effect. The present study was designed to compare the possible protective role of ghrelin to Wharton jelly-derived mesenchymal stem cells (WJ-MSCs) as well as their combined effect in doxorubicin-induced cardiotoxicity in rats. Forty adult male albino rats were divided into five groups: Group (I): normal control group, Group (II): DOX induced cardiotoxicity group, Group (III): ghrelin treated group, Group (IV): MSCs treated group and Group (V): ghrelin and MSCs (combined) treated group. Cardiac enzymes, oxidative stress markers, apoptotic markers in cardiac tissue and cardiac performance parameters using Langendorff apparatus and echocardiography, were assessed. At the end of the experiment, histopathological evaluation of the injured myocardium was conducted using hematoxylin and eosin (H&E), Masson’s trichrome staining, and immunohistochemical analysis for nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Our results revealed a significant amelioration of the aforementioned parameters almost towards normal values in the three treatment groups. Histopathological examination and immunohistochemical assessment of Nrf2 & HO-1 revealed improvement in the three treated groups, particularly those receiving stem cell therapy.

Methotrexate (MTX) is still a broad-spectrum drug that has been used for almost a century for leukemia, rheumatoid arthritis, ectopic pregnancy. This study investigates the protective effects of coenzyme Q10 (CoQ10) on MTX induced gonadotoxicity. Twenty-four female wistar albino rats were divided into four groups. Control group; 1 ml corn oil was applied by oral gavage (p.o.). CoQ10 group; 100 mg/kg CoQ10 (in 1 ml corn oil) was applied by p.o. for seven days. MTX group; 20 mg/kg MTX intraperitoneal (i.p.) was used one time on the first day of the experiment. MTX + CoQ10 group; 20 mg/kg MTX i.p. one time and 100 mg/kg CoQ10 (in 1 ml corn oil) was applied p.o. for seven days. At the end of the experiment, all animals were euthanized under anesthesia, and blood samples were taken from intracardiac. The both sides ovaries were taken out and were put in to neutral formalin. Biochemical analysis for serum anti-mullerian hormone (AMH), flow cytometry for apoptosis (Annexin V), and histopathologic analysis with follicle counting were performed in ovarian tissues. According to results of follicle counting, apoptosis, morphometric and AMH analysis; there was no statistically significant difference in terms of follicle numbers and ovarium diameter between all groups. However, apoptosis significantly increased in the MTX group and decreased in the MTX + CoQ10 group. AMH level was decreased in the MTX group and interestingly significantly increased in the only CoQ10 treatment group and. As a result, CoQ10 has protective effects in terms of apoptosis and AMH against MTX induced gonadotoxicity.

Hepatocellular carcinoma (HCC) is a type of primary liver cancer characterized by inflammation and liver damage. It is a serious disease that progresses rapidly and is often diagnosed at an advanced stage. Voacangine (VCG), a well-known alkaloid, has been shown to possess anti-inflammatory and antitumor properties. This study investigated the effectiveness of VCG in counteracting diethylnitrosamine (DEN)-induced HCC by targeting the ERK/PI3K/Akt signaling pathways. Male Wistar albino rats were divided into four groups: a normal control group (NC) receiving PBS, a VCG-alone group (5 mg/kg body weight), a DEN-induced HCC model group (100 mg/kg in drinking water), and a DEN + VCG group (5 mg/kg body weight) for 22 weeks. Molecular docking studies, specifically XP and IFD using Schrodinger’s Glide Module, were performed and validated via in vivo and in silico experiments. The results revealed that VCG significantly reduced several indicators of HCC progression in DEN-treated rats, including body weight loss, increased liver weight, elevated hepatic marker enzymes, oxidative stress, inflammation, and architectural damage to hepatocytes. Furthermore, VCG increased the mRNA expression of proapoptotic genes such as Bcl-2-associated protein x (Bax), the tumor protein p53 (p53), caspase-9, and caspase-3 while decreasing antiapoptotic B-cell lymphoma 2 (Bcl-2) levels. Oral administration of VCG to rats intoxicated with DEN resulted in marked down-regulation of the hepatic PI3K, AKT, and ERK gene expressions. These findings suggest that VCG has the potential to prevent liver cancer. Its multitarget efficacy, particularly its ability to inhibit the PI3K/Akt/ERK signaling pathway, was demonstrated through both in vivo and in silico studies, supporting its use as a potential therapeutic agent for hepatic cancer.

Gentamicin (GEN), commonly used to treat gram-negative bacterial infections, can cause testicular damage, maybe by increasing oxidative stress. Gallic acid (GA) a polyphenolic acid, has antioxidant, anti-bacterial, anti-viral, and anti-allergic activities. The study aimed to investigate the effects of GA on GEN-induced testicular toxicity. Thirty Wistar rats were randomly divided into five groups: Control, which received only normal saline, and GEN, which received 100 mg/kg/day of GEN intra-peritoneally for six days. The rats in groups 3, 4, and 5 received GA by gavage at 60, 90, and 120 mg/kg for 14 consecutive days and six intraperitoneal injections of 100 mg/kg/day of GEN from nine to fourteen days, respectively. After the last treatment, rats were sacrificed, and testicular weights, sperm parameters (viability, number, and motility of sperm), serum testosterone and gonadotropin hormones, tissue superoxide dismutase and malondialdehyde, and testicular histology were evaluated. Gentamicin reduced sperm count, viability, motility, and testicular-weight, as well as serum levels of testosterone, FSH, LH, and SOD. Testicular-weight in GEN + 60, 90, and 120 mg/kg GA groups had significantly increased compared to GEN group. All GA doses in the GEN + GA groups, increased FSH (except dose of 60), LH and testosterone (p < 0.05). In the rats received 120 mg/kg GA, MDA decreased and SOD increased significantly (p < 0.05). Histopathological findings showed that the administration of GA could significantly reduce the adverse effects of GEN on the structure of seminiferous tubules and the number of germ cells (p < 0.05). Administration of GA adjunct with GEN might be beneficial in men who were under GEN therapy.