Journal of Molecular Histology最新文献

Conservation of the genetic diversity through skin and cartilage biobanks represents an essential strategy for maintaining biodiversity. Biobanks for the wild species of the order Rodentia have been little studied. Considering that the cryopreservation technique has specific relationships with the tissue and species of interest, we propose investigating different techniques for preserving tissue integrity and cell viability after cartilage and skin culture from Spix's yellow-toothed cavies. Subsequently, two techniques [solid-surface vitrification (SSV) vs. slow freezing (SF)] were used for cartilage and skin cryopreservation. Tissues not subjected to cryopreservation were used as controls. All tissues were evaluated for morphology and proliferation by histological techniques. Moreover, fragments were cultured, and cells were evaluated for viability, proliferation, metabolism, and apoptosis. Regardless of the cryopreservation technique, no differences were observed for the thickness of the epidermis, dermis, skin, spinous and basal layers, fibroblasts, and proliferative activity regarding the number of nucleolar organizer regions (NOR). SSV ensured better maintenance of epidermal cells, normal chondrocytes, filled gaps, collagen fibers, proliferative activity by NOR area/cell, and reduced perinuclear halos and empty gaps compared to SF. SF ensured the conservation of corneum thickness compared to the control. Although both techniques promoted cell recovery after culture, cells from SF resulted in better subconfluence time and day with cell growth around fragments compared to SSV. In conclusion, both cryopreservation techniques resulted in viable cells after culture. However, SSV promoted better maintenance of tissue morphological integrity, and SF ensured the preservation of all cell quality parameters in Spix's yellow-toothed cavies.

Type 2 diabetes mellitus (T2DM) is a global health concern with increasing prevalence. Mathurameha, a Thai herbal formula, has shown promising glucose-lowering effects and positive impacts on biochemical profiles in diabetic rats. The present study investigated the protective effects of Mathurameha on cardiovascular complications in high-fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic rats using histological and proteomic analyses. Thirty-five male Sprague-Dawley rats were divided into seven groups: normal diet (ND), ND with aqueous extract (ND + AE450), ND with ethanolic extract (ND + EE200), diabetes (DM), DM with AE (DM + AE450), DM with EE (DM + EE200), and DM with metformin (DM + Met). Mathurameha, especially at 200 mg/kg EE, significantly reduced adipocyte size, cardiac and vascular abnormalities, collagen deposition, and arterial wall thickness in DM rats. Proteomic analysis of rat aortas revealed 30 significantly altered proteins among the ND, DM, and DM + EE200 groups. These altered proteins are involved in various biological processes related to diabetes. Biochemical assays showed that Mathurameha reduced lipid peroxidation (MDA), increased antioxidant levels (GSH), and decreased the expression of inflammatory markers (ICAM1, TNF-α). In conclusion, Mathurameha exhibited significant protective effects against cardiovascular complications in HFD/STZ-induced type 2 diabetic rats through its antioxidant and anti-inflammatory properties.

The oral biguanide metformin is used to treat type 2 diabetic mellitus (T2DM). Anti-cancer effects have been proven by metformin in different hormone-sensitive tumors, including breast, pancreatic, colon, and prostate cancer. Therefore, we investigated whether metformin could defend against small intestine damage in Dunning's prostate cancer. The study divided the six groups of male Copenhagen rats into the following categories: control, diabetic (D), cancer (C), diabetic + cancer (DC), cancer + metformin (CM), and diabetic + cancer + metformin (DCM). After sacrifice, the small intestines were removed to assess biochemical markers and histopathological evaluation. Biochemical evaluations showed that glutathione (reduced) levels and other enzyme activities related antioxidant systems, paraoxonase, sodium potassium ATPase, acetylcholinesterase activities were decreased. In contrast, lipid peroxidation, total oxidant status, reactive oxygen species, interleukin-1β, interleukin-6, tumor necrosis factor-α, sucrase, maltase, trypsin, myeloperoxidase, xanthine oxidase activities, protein carbonyl contents and sialic acid levels were raised in the damaged groups. Treatment with metformin restored all of this. The histological assessment revealed moderate to severe damage in the small intestine following processes D and C. According to the study's findings, metformin treatment led to a notable decline in histopathological damage in the C and DC. A slight lowering in inflammatory cells and an improvement in the damaged gland integrity in the small intestine were noted with metformin treatment.​ Metformin use protected the small intestinal tissue damage and decreased oxidative stress.

The high lethality caused by paraquat (PQ) poisoning has attracted much attention in public and human health due to its high toxicity and lethality. However, the understanding of the mechanism of PQ-induced apoptosis from the perspective of organelles, especially inter-organelle interactions, is still scarce. Exploring the linkage of multiple organelles during PQ poisoning and the molecular mechanisms of PQ poisoning under its mediation will help to gain insight into the mode of PQ poisoning at the organelle level. In this study, we observed that a certain dose of PQ gavage induced oxidative stress, mitochondrial dysfunction and endoplasmic reticulum stress in rat lung tissue cells. PQ toxicity led to the occurrence of Ca²⁺ overload in the endoplasmic reticulum, and the activated BIP and CHOP pathways directly/indirectly led to the expression of apoptogenic factors Caspase family factors. In addition, PQ promoted Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ uptake by mitochondria, which induced the disruption of Bax/Bcl-2 channel proteins in response to the IP₃R/RyR/VDAC1&2/MCU Ca²⁺ axis thereby leading to the release of CytoC, which ultimately induced endoplasmic reticulum stress and apoptotic cell death. In addition, 10 differential proteins were screened and validated by proteomics that may act as upstream and downstream active factors of mitochondria-endoplasmic reticulum interaction-mediated biotoxicity. Our findings provide new perspectives for researchers to explore the toxicity mechanisms of PQ to reduce their adverse effects.

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC) and is characterized by its heterogeneity and poor prognosis. The role of ribosomal proteins RPLP0, RPLP1 and RPLP2 in multiple cancers has been implicated. However, their function in LUAD and their correlation with the poor prognosis of LUAD remains elusive. In this study, we performed a comprehensive bioinformatic analysis of the impact of these ribosomal proteins on LUAD. Our findings reveal that RPLP0, RPLP1 and RPLP2 are overexpressed in LUAD, which are likely attributed to abnormal copy number variations and decreased methylation levels of their promoters. LUAD patients with high expression of RPLP0, RPLP1 or RPLP2 have worse clinical outcomes in terms of overall survival (OS), first progression (FP) and post-progression survival (PPS), indicating poor prognosis. Moreover, the expression of RPLP0, RPLP1 and RPLP2 affects immune cell infiltration in LUAD tissues. Finally, we identified multiple existing drugs that may inhibit the expression of RPLP1 and RPLP2. Collectively, our data implicate the oncogenic role of RPLP0, RPLP1 and RPLP2 in LUAD and underscore their prognostic value in LUAD patients.

Diabetic cognitive dysfunction (DCD) is a complication of diabetes that seriously affects quality of life. Glucocorticoid-induced transcript 1 (GLCCI1) has been found to be involved in inflammation, apoptosis and autophagy in various diseases. However, the distribution of GLCCI1 in the brain and its role in DCD have not yet been revealed. In addition, the potential therapeutics effects of salidroside (SAL), a phenyl propyl glycoside compound known for its neuroprotective effects in treating DCD are unknow. In the present study, we found that GLCCI1 was localized in hippocampal neurons. C57BL/6 J mice with DCD presented downregulation of GLCCI1 and Bcl-2 and upregulation of p-STAT3/STAT3, Bax, Cleaved Caspase-3/Caspase-3. Overexpression of GLCCI1 or SAL administration relieved DCD, reversed the changes in the expression of these cytokines, and alleviated morphological alterations in hippocampal neurons. Interestingly, SAL alleviated DCD and attenuated the expression of GLCCI1 and p-STAT3, showing similar effects as GLCCI1 overexpression. These findings suggest that the GLCCI1/STAT3 axis plays a crucial role in DCD and is involved in SAL-mediated attenuation of DCD.

Heavy metals may cause structural and functional changes in organs. Cadmium, taken into the body through oral and respiratory routes, can lead to lesions. Cadmium may lead to lesions by accumulating in organs. The lungs are significantly affected by cadmium. Melatonin, an antioxidant hormone with therapeutic effects, is secreted by the pineal gland. The aim of the study is to treat cadmium-induced lesions in the lungs of pregnant mice with Melatonin. Four groups were created with 24 pregnant mice, named Control, Cadmium Chloride, Melatonin, and Melatonin + Cadmium Chloride groups (n: 6) Cadmium Chloride (2 mg/kg/bw) and Melatonin (3 mg/kg/bw) were given orally through gavage during pregnancy (21 days) After routine histological procedures, the lung tissues were stained with Hematoxylin-Eosin and evaluated under a light and electron microscope. ANOVA tests were applied for one-way analysis of variance, and LSD tests were applied for pairwise comparisons (p < 0.05) The average lung weight decreased in the Cadmium Chloride group (p: 0.03) The average lung weight in the Cadmium Chloride + Melatonin group was found to be close to the control group (p: 0.06) Cadmium Chloride caused thickening of the lung alveolar wall, inflammatory cell infiltration, and fibrin deposition. Because the lesions were not observed in the Melatonin group, lesions may be prevented by melatonin. Additional studies may be useful to determine the protective effect of Melatonin at different doses of Cadmium Chloride.

Hepatocellular carcinoma (HCC) presents challenges due to inadequate early monitoring and diagnostic precision, resulting in rising incidence and mortality rates. Identifying reliable predictive biomarkers is imperative. This study investigates PODXL expression in HCC and its mechanisms in tumor onset and progression. Clinical samples were analyzed for PODXL expression in HCC tissues, correlating with clinical features and prognosis. In vitro experiments and bioinformatics analysis validated PODXL's role in HCC, particularly in HCCLM3 cells, highlighting its impact on proliferation, invasion, and metastasis. Enhanced PODXL expression, associated with poor prognosis, was observed in HCC tissues and cells. Downregulating PODXL reduced HCCLM3 cell proliferation, invasion, and migration, while promoting apoptosis. Bioinformatics analysis linked abnormal PODXL expression to the PI3K/AKT pathway. Moreover, PODXL downregulation and PI3K/AKT activation verified PODXL's role in promoting HCCLM3 cell progression via this pathway. This study underscores PODXL's significance in HCC prognosis and suggests its potential as a diagnostic or therapeutic target.

This study tested the hypothesis that empagliflozin (EMPA) therapy effectively protected renal and heart functions via downregulating reactive oxygen species (ROS) and activating AMPK signaling in cardiorenal syndrome (CRS) (induced by doxorubicin-5/6 nephrectomy) rats. In vitro result showed that underwent p-Cresol treatment, the H9C2/NRK-52E cell viabilities, were significantly suppressed, whereas cellular levels of ROS and early/late apoptosis of these cells were significantly increased that were significantly reversed by EMPA treatment (all p < 0.001). The protein levels of the cell-stress/oxidative signaling (p-PI3K/p-Akt/p-mTOR/NOXs/p-DRP1) were significantly activated, whereas the mitochondrial biogenesis signaling (p-AMPK/SIRT-1/TFAM/PGC-1α) was significantly repressed in these two cell lines treated by p-Cresol and all of these were significantly reversed by EMPA treatment (all p < 0.001). Male-adult-SD rats were categorized into groups 1 [sham-operated control (SC)]/2 [SC + high protein diet (H^PD) since day 1 after CKD induction]/3 (CRS + H^PD)/4 (CRS + H^PD+EMPA/20 mg/kg/day) and heart/kidney were harvested by day 60. By day 63, the renal function parameters (creatinine/BUN/proteinuria)/renal artery restrictive index/cellular levels of ROS/inflammation were significantly increased in group 3 than in groups 1/2, whereas heart function exhibited an opposite pattern of ROS among the groups, and all of these parameters were significantly reversed by EMPA treatment (all p < 0.0001). The protein levels of inflammation/ oxidative-stress/cell-stress signalings were highest in group 2, lowest in group 1 and significantly lower in group 4 than in group 2, whereas the AMPK-mitochondrial biogenesis displayed an opposite manner of oxidative-stress among the groups (all p < 0.0001). EMPA treatment effectively protected the heart/kidney against CRS damage via suppressing ROS signaling and upregulating AMPK-mediated mitochondrial biogenesis.