Identification of potential biomarkers for melanoma cancer (black tumor) using bioinformatics strategy: a study based on GEO and SRA datasets.

Melanoma, a highly invasive type of skin cancer that penetrates the entire dermis layer, is associated with increased mortality rates. Excessive exposure of the skin to sunlight, specifically ultraviolet radiation, is the underlying cause of this malignant condition. The appearance of unique skin moles represents a visible clue, referred to as the "ugly duckling" sign, indicating the presence of melanoma and its association with cellular DNA damage. This research aims to explore potential biomarkers derived from microarray data, employing bioinformatics techniques and methodologies, for a thorough investigation of melanoma skin cancer. The microarray dataset for melanoma skin cancer was obtained from the GEO database, and thorough data analysis and quality control measures were performed to identify differentially expressed genes (DEGs). The top 14 highly expressed DEGs were identified, and their gene information and protein sequences were retrieved from the NCBI gene and protein database. These proteins were further analyzed for domain identification and network analysis. Gene expression analysis was conducted to visualize the upregulated and downregulated genes. Additionally, gene metabolite network analysis was carried out to understand the interactions between highly interconnected genes and regulatory transcripts. Molecular docking was employed to investigate the ligand-binding sites and visualize the three-dimensional structure of proteins. Our research unveiled a collection of genes with varying expression levels, some elevated and others reduced, which could function as promising biomarkers closely linked to the development and advancement of melanoma skin cancer. Through molecular docking analysis of the GINS2 protein, we identified two natural compounds (PubChem-156021169 and PubChem-60700) with potential as inhibitors against melanoma. This research has implications for early detection, treatment, and understanding the molecular basis of melanoma.

Increased NOTCH1 expression is associated with low survival in moderate/ poor differentiated human oral squamous cell carcinoma patients.

Notch deregulation has been reported in various types of cancers, including Oral squamous cell carcinomas (OSCCs). The role of Notch1 signaling in oral squamous cell carcinoma (OSCC) remains poorly understood. In this study, NOTCH1 was aberrantly expressed in human oral cancer tissues compared with that in normal marginal tissues and was associated with poor prognosis. The positive Notch 1 expression was significantly associated with poor tumor differentiation status. Kaplan-Meier survival curves revealed that elevated cytoplasmic NOTCH1 expression levels in OSCC patients were associated with poor overall survival. Moreover, multivariate COX proportional hazard models revealed that T N status, AJCC stage histological grade were independent prognostic factors for survival. Our result clearly demonstrates the oncogenic role of Notch1 in oral cancer and Notch1 may be a useful biomarker to target oral cancer patients.

Prognostic and Clinical Implications of UNC13C expression in Hepatocellular Carcinoma Patients.

Aberrant expression of UNC13C (Unc-13 Homolog C) has been observed during the progression of oral squamous cell carcinoma. However, the expression pattern and clinical relevance of UNC13C in Hepatocellular carcinoma (HCC) remain to be elucidated. The purpose of this study is to examine UNC13C expression in HCC and explore its role in clinicopathological factor or prognosis in HCC. Two hundred and sixty-five patients diagnosed with HCC were included in the present study. The expression of UNC13C in HCC tissues was analyzed by immunohistochemistry analysis. The relationship between UNC13C protein and clinicopathological characteristics in HCC was investigated. Moreover, the high expression of UNC13C was significantly correlated with T stage, AJCC stage and overall survival rates. Cox regression analysis identified UNC13C as an independent prognostic indicator for HCC patients. UNC13C might be a prognostic biomarker and therapeutic target in HCC. Further studies with larger sample sets are needed to understand the clinical implications of UNC13C in hepatocellular carcinoma.

The function of long non-coding RNA SNHG11 and its working mechanism in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) seriously affects woman's health. The present work is to study the working mechanism of lncRNA SNHG11 in TNBC. The expressions of SNHG11, microRNA (miR)- 7-5p, specificity protein 2 (SP2) and mucin 1 (MUC-1) in TNBC tissues and cells were detected. SNHG11, miR-7-5p and SP2 expressions were then evaluated for TNBC cell malignant behaviors. The relationships among SNHG11, miR-7-5p and SP2 were predicted and verified. Finally, the binding of the transcription factor SP2 to MUC-1 promoter was detected. Abnormally elevated SNHG11, SP2 and MUC-1 expressions were observed in cultured TNBC cells and tumor tissues. SNHG11 knockdown in TNBC cells. Silencing SP2 weakened the promoting effect of SNHG11 on TNBC progression. SNHG11 negatively regulated miR-7-5p expression and positively regulated SP2 expression. SP2 bound to the P2 site of MUC-1 promoter, and SP2 knockdown suppressed MUC-1 expression. It was demonstrated that lncRNA SNHG11 promoted TNBC cell malignant behaviors to facilitate TNBC progression. The study is first of its kinds to unravel the potential of lncRNA SNHG11 in relation to TNBC.

Apocynin abrogates methotrexate-induced nephrotoxicity: role of TLR4/NF-κB-p65/p38-MAPK, IL-6/STAT-3, PPAR-γ, and SIRT1/FOXO3 signaling pathways.

The present study was designed to evaluate the potential renoprotective impacts of apocynin (APC) against nephrotoxicity induced by methotrexate (MTX) administration. To fulfill this aim, rats were allocated into four groups: control; APC (100 mg/kg/day; orally); MTX (20 mg/kg; single intraperitoneal dose at the end of the 5th day of the experiment); and APC +MTX (APC was given orally for 5 days before and 5 days after induction of renal toxicity by MTX). On the 11th day, samples were collected to estimate kidney function biomarkers, oxidative stress, pro-inflammatory cytokines, and other molecular targets. Compared to the MTX control group, treatment with APC significantly decreased urea, creatinine, and KIM-1 levels and improved kidney histological alterations. Furthermore, APC restored oxidant/antioxidant balance, as evidenced by a remarkable alleviation of MDA, GSH, SOD, and MPO levels. Additionally, the iNOS, NO, p-NF-κB-p65, Ace-NF-κB-p65, TLR4, p-p38-MAPK, p-JAK1, and p-STAT-3 expressions were reduced, while the IκBα, PPAR-γ, SIRT1, and FOXO3 expressions were significantly increased. In NRK-52E cells, MTX-induced cytotoxicity was protected by APC in a concentration-dependent manner. In addition, increased expression of p-STAT-3 and p-JAK1/2 levels were reduced in MTX-treated NRK-52E cells by APC. The in vitro experiments revealed that APC-protected MTX-mediated renal tubular epithelial cells were damaged by inhibiting the JAK/STAT3 pathway. Besides, our in vivo and in vitro results were confirmed by predicting computational pharmacology results using molecular docking and network pharmacology analysis. In conclusion, our findings proved that APC could be a good candidate for MTX-induced renal damage due to its strong antioxidative and anti-inflammatory bioactivities.

Protective role of naftidrofuryl against methotrexate-induced testicular damage via the amelioration of the p53/miRNA-29a/CDC42 apoptotic pathway, inflammation, and oxidative stress.

This study aimed to assess the possible protective effects of naftidrofuryl (Naf) against methotrexate (MTX)-induced testicular toxicity in rats. Male rats were randomly distributed into four groups: control, Naf, MTX, and MTX+Naf groups. MTX administration induced oxidative stress, inflammation, and apoptosis in the testicular tissue, while pretreatment with Naf attenuated these pathways. Naf pretreatment significantly decreased malondialdehyde and interleukin-6 contents, microRNA-29a (miRNA-29a) expression level, and nuclear factor kappa B and p53 immunostaining in the testicular tissues compared to the MTX group. Conversely, it significantly increased Johnsen's score, serum testosterone level, serum total antioxidant capacity, testicular superoxide dismutase activity, testicular catalase activity, and testicular cell division cycle 42 (CDC42) expression compared to the MTX group. In conclusion, Naf exerted a significant protective effect against MTX-induced testicular toxicity via antioxidant and anti-inflammatory mechanisms and modulating the p53/miRNA-29a/CDC42 apoptotic pathway.

Lansoprazole attenuates cyclophosphamide-induced cardiopulmonary injury by modulating redox-sensitive pathways and inflammation.

Cyclophosphamide (CPA) is a classical chemotherapeutic drug widely used as an anticancer and immunosuppressive agent. However, it is frequently associated with significant toxicities to the normal cells of different organs, including the lung and heart. Lansoprazole (LPZ), a proton pump inhibitor (PPI), possesses antioxidant and anti-inflammatory properties. The current study investigated how LPZ protects against CPA-induced cardiac and pulmonary damage, focusing on PPARγ, Nrf2, HO-1, cytoglobin, PI3K/AKT, and NF-κB signaling. Animals were randomly assigned into four groups: normal control group (received vehicle), LPZ only group (Rats received LPZ at a dose of 50 mg/kg/day P.O. for 10 days), CPA group (CPA was administered (200 mg/kg) as a single i.p. injection on the 7th day), and cotreatment group (LPZ plus CPA). Histopathological and biochemical analyses were conducted. Our results revealed that LPZ treatment revoked CPA-induced heart and lung histopathological alterations. Also, LPZ potently mitigated CPA-induced cardiac and pulmonary oxidative stress through the activation of PPARγ, Nrf2/HO-1, cytoglobin, and PI3K/AKT signaling pathways. Also, LPZ effectively suppressed inflammatory response as evidenced by down-regulating the inflammatory strategic controller NF-κB, MPO, and pro-inflammatory cytokines. The present findings could provide a mechanistic basis for understanding LPZ's role in CPA-induced cardiopulmonary injury through the alleviation of oxidative stress and inflammatory burden.

Candesartan Protects Against Cadmium-Induced Hepatorenal Syndrome by Affecting Nrf2, NF-κB, Bax/Bcl-2/Cyt-C, and Ang II/Ang 1-7 Signals.

Cadmium (Cd) is a serious pollutant in the environment. Candesartan is an angiotensin II (Ang II) receptor antagonist with promising diverse health benefits. The current study is planned to investigate the hepatorenal protective effects of candesartan against Cd-induced hepatic and renal intoxication. Our results demonstrated that candesartan effectively attenuated Cd-induced hepatorenal intoxication, as evidenced by improving hepatic and renal function biomarkers. Besides, candesartan reversed hepatic and renal histopathological abrasions induced by Cd toxicity. Candesartan antioxidant effect was mediated by Nrf2 activation. Also, candesartan suppressed hepatorenal inflammation by modulating NF-κB/IκB. Moreover, candesartan attenuated Cd hepatorenal apoptosis by upregulating Bcl-2 and downregulating Bax and Cyt-C proteins. Interestingly, these effects are suggested to be an outcome of modulating of Ang II/Ang 1-7 signal. Overall, our findings revealed that candesartan could attenuate Cd-induced hepatorenal intoxication through modulation of Nrf2, NF-κB/IκB, Bax/Bcl-2/Cyt-c, and Ang II/Ang 1-7 signaling pathways.

Bioinformatics role of the WGCNA analysis and co-expression network identifies of prognostic marker in lung cancer.

Lung cancer is the most talked about cancer in the world. It is also one of the cancers that currently has a high mortality rate. The aim of our research is to find more effective therapeutic targets and prognostic markers for human lung cancer. First, we download gene expression data from the GEO database. We performed weighted co-expression network analysis on the selected genes, we then constructed scale-free networks and topological overlap matrices, and performed correlation modular analysis with the cancer group. We screened the 200 genes with the highest correlation in the cyan module for functional enrichment analysis and protein interaction network construction, found that most of them focused on cell division, tumor necrosis factor-mediated signaling pathways, cellular redox homeostasis, reactive oxygen species biosynthesis, and other processes, and were related to the cell cycle, apoptosis, HIF-1 signaling pathway, p53 signaling pathway, NF-κB signaling pathway, and several cancer disease pathways are involved. Finally, we used the GEPIA website data to perform survival analysis on some of the genes with GS > 0.6 in the cyan module. CBX3, AHCY, MRPL12, TPGB, TUBG1, KIF11, LRRC59, MRPL17, TMEM106B, ZWINT, TRIP13, and HMMR was identified as an important prognostic factor for lung cancer patients. In summary, we identified 12 mRNAs associated with lung cancer prognosis. Our study contributes to a deeper understanding of the molecular mechanisms of lung cancer and provides new insights into drug use and prognosis.

The use of patient-specific stem cells in different autoimmune diseases.

Autoimmune diseases are developed when the immune system mistakenly attacks the body's cells. These inflammatory disorders can be inherited or triggered by external forces, such as type 1 diabetes, which is caused by the immune system's destruction of pancreatic beta cells. So far, stem cells such as hESC and iPSC have been used to treat autoimmune disorders such as type 1 diabetes, rheumatoid arthritis (RA), multiple sclerosis (MS), and systemic lupus erythematosus (SLE), although these procedures have certain ethical concerns. On the other hand, bone marrow-derived mesenchymal stem cells (BM-MSC) are thought to be the best source of stem cells. Later, it was shown that mesenchymal stem cells produced from autologous adipose tissues have a great potential for producing huge volumes of stem cells. In-vitro and in-vivo investigations using autologous hematopoietic stem cells and autologous mesenchymal stem cells have been carried out on various rodent and human models, while clinical trials for inflammatory diseases such as multiple sclerosis and diabetes mellitus have yielded promising results. We attempted to summarise the usage of diverse stem cells in the therapy of various autoimmune disorders in this review. Shortly, we expect that the use of autologous stem cells will provide a new perspective on the treatment of autoimmune disorders.

L. Cucurbita pepo modulates contact dermatitis in depressed rats through downregulation of proinflammatory cytokines and upregulation of antioxidant status.

Introduction: The link between psychological stress and skin diseases, such as atopic dermatitis is established. Pumpkin was proved to have antioxidant, anti-inflammatory and accelerating wound healing potential. Aim: To assess the efficacy of pumpkin fruit (Cucurbita pepo L.) extract (PE) in relieving contact dermatitis (CD) in depressed rats compared to a standard treatment of CD and explore the mechanism behind this effect. Material and methods: Thirty male albino rats were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks for induction of depression, then exposed to 1-fluoro-2,4-dinitrofluorobenzene (DNFB) for 2 weeks for induction of CD. The rats were then divided into 3 groups (n = 10 each); the positive control, Betamethasone-treated, and PE-treated groups. Depression was confirmed by the forced swim test and measuring the serum corticosterone level. Proinflammatory cytokines tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were measured in the skin and serum and their mRNA levels were assessed using qRT-PCR. Oxidant/antioxidant profile including levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) was assessed in the skin and serum. Histopathological assessment of skin samples was performed and CD4 and CD68 immunoexpression was assessed. Results: The used PE included a large amount of oleic acid (about 56%) and a small amount of linoleic acid (about 1%). The topical application of PE significantly attenuated inflammation and oxidative changes attributed to CD associated with chronic stress-induced depression comparable to the standard treatment of CD. PE significantly alleviated signs and histopathological score of CD (p < 0.001) through the significant down-regulation of pro-inflammatory cytokines and the significant up-regulation of antioxidants in the skin. Significant down-regulation (p < 0.001) of TNF-α, IL-6, COX-2 and iNOS gene expression in the PE-treated group confirmed the anti-inflammatory action of PE. Conclusions: The pumpkin extract, applied topically in CD associated with depression, could be an alternative as well as preventive approach in treating CD. Anti-inflammatory and antioxidants activity of pumpkin is a proposed mechanism behind this effect. Further studies to test this effect on volunteer patients of CD are recommended.

Decapeptide from Potato Hydrolysate Induces Myogenic Differentiation and Ameliorates High Glucose-Associated Modulations in Protein Synthesis and Mitochondrial Biogenesis in C2C12 Cells.

Sarcopenia is characterized as an age-related loss of muscle mass that results in negative health consequences such as decreased strength, insulin resistance, slowed metabolism, increased body fat mass, and a substantially diminished quality of life. Additionally, conditions such as high blood sugar are known to further exacerbate muscle degeneration. Skeletal muscle development and regeneration following injury or disease are based on myoblast differentiation. Bioactive peptides are biologically active peptides found in foods that could have pharmacological functions. The aim of this paper was to investigate the effect of decapeptide DI-10 from the potato alcalase hydrolysate on myoblast differentiation, muscle protein synthesis, and mitochondrial biogenesis in vitro. The treatment of C2C12 myoblasts with DI-10 (10 µg/mL) did not induce cell death. DI-10 treatment in C2C12 myoblast cells accelerates the phosphorylation of promyogenic kinases such as ERK, Akt and mTOR proteins in a dose-dependent manner. DI-10 improves myotubes differentiation and upregulates the expression of myosin heavy chain (MyHC) protein in myoblast cells under differentiation medium with high glucose. DI-10 effectively increased the phosphorylation of promyogenic kinases Akt, mTOR, and mitochondrial-related transcription factors AMPK and PGC1α expression under hyperglycemic conditions. Further, decapeptide DI-10 decreased the expression of Murf1 and MAFbx proteins, which are involved in protein degradation and muscle atrophy. Our reports support that decapeptide DI-10 could be potentially used as a therapeutic candidate for preventing muscle degeneration in sarcopenia.

A Novel Sprague-Dawley Rat Model Presents Improved NASH/NAFLD Symptoms with PEG Coated Vitexin Liposomes.

Chronic liver disease (CLD) is a global threat to the human population, with manifestations resulting from alcohol-related liver disease (ALD) and non-alcohol fatty liver disease (NAFLD). NAFLD, if not treated, may progress to non-alcoholic steatohepatitis (NASH). Furthermore, inflammation leads to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Vitexin, a natural flavonoid, has been recently reported for inhibiting NAFLD. It is a lipogenesis inhibitor and activates lipolysis and fatty acid oxidation. In addition, owing to its antioxidant properties, it appeared as a hepatoprotective candidate. However, it exhibits low bioavailability and low efficacy due to its hydrophobic nature. A novel rat model for liver cirrhosis was developed by CCL4/Urethane co-administration. Vitexin encapsulated liposomes were synthesized by the 'thin-film hydration' method. Polyethylene glycol (PEG) was coated on liposomes to enhance stability and stealth effect. The diseased rats were then treated with vitexin and PEGylated vitexin liposomes, administered intravenously and orally. Results ascertained the liposomal encapsulation of vitexin and subsequent PEG coating to be a substantial strategy for treating liver cirrhosis through oral drug delivery.

Bovine serum albumin functionalized blue emitting Ti3 C2 MXene quantum dots as a sensitive fluorescence probe for Fe3+ ion detection and its toxicity analysis.

In the present work, an improved class of protein functionalized fluorescent 2D Ti3 C2 MXene quantum dots (MXene QDs) was prepared using a hydrothermal method. Exfoliated 2D Ti3 C2 sheets were used as the starting precursor and transport protein bovine serum albumin (BSA) was used to functionalize the MXene QDs. BSA-functionalized MXene QDs exhibited excellent photophysical property and stability at various physiological parameters. High-resolution transmission electron microscopy analysis showed that the BSA@MXene QDs were quasispherical in shape with a size of ~2 nm. The fluorescence intensity of BSA@MXene QDs was selectively quenched in the presence of Fe3+ ions. The mechanism of fluorescence quenching was further substantiated using time-resolved fluorescence and Stern-Volmer analysis. The sensing assay showed a linear response within the concentration range 0-150 µM of Fe3+ ions with excellent limit of detection. BSA@MXene QDs probe showed good selectivity toward ferric ions even in the presence of other potential interferences. The practical applicability of BSA@MXene QDs was further tested in real samples for Fe3+ ion quantification and the sensor had good recovery rates. The cytotoxicity studies of the BSA@MXene QDs toward the human glioblastoma cells revealed that BSA@MXene QDs are biocompatible at lower doses and showed significant cytotoxicity at higher dosages.

Construction of Adipogenic ceRNA Network Based on lncRNA Expression Profile of Adipogenic Differentiation of Human MSC Cells.

The Long non-coding RNA (lncRNA) expression profile data of ten samples including human Mesenchymal Stem Cell (MSC) adipogenic differentiation 0, 3, and 6 days from the GEO database, and then perform gene ID conversion, BLAST comparison, and annotation marking. Finally, group A (treatment group on day 3 of differentiation and control group on day 0 of differentiation) obtained a total of 1180 mRNA and 185 lncRNA; group B (treatment group on day 6 of differentiation and control group on day 0 of differentiation). A total of 1376 mRNA and 206 lncRNA were obtained. Finally, we processed the differential lncRNAs and mRNAs obtained in the two groups, and obtained 113 shared differential lncRNAs to further predict the targeted miRNA, a total of 815 lncRNA-miRNA pairs. The targeted mRNA was further predicted, and the grouped differential mRNAs were combined to obtain 64 differential mRNAs. In the end, we obtained 216 ceRNAs containing 26 lncRNAs, 27 miRNAs and 64 mRNAs. We found that the mRNAs in the ceRNA network were mainly enriched with 45 Gene Ontology (GO) terms, mainly including glucose homeostasis mechanism and insulin stimulation response. 69 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were mainly enriched. It mainly includes many pathways related to lipid metabolism such as Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), Rap1, cAMP, mitogen-activated protein kinase (MAPK), Ras, hypoxia inducible factor-1 (HIF-1), PI3K-Akt, insulin signaling and so on. In the end, we identified 216 ceRNA regulatory relationships related to obesity research. Our research provides a clearer direction for understanding the molecular mechanism of obesity, the screening and determination of drug targets biomarkers in the future.

Hepatoprotective effect of acetovanillone against methotrexate hepatotoxicity: Role of Keap-1/Nrf2/ARE, IL6/STAT-3, and NF-κB/AP-1 signaling pathways.

This study targeted to examine the protective effects of acetovanillone (AV) against methotrexate (MTX)-induced hepatotoxicity. Thirty-two rats were allocated into four groups of eight animals; Group 1: Normal; Group 2: administered AV (100 ml/kg; P.O.) for 10 days; Group 3: challenged with MTX (20 mg/kg, i.p; single dose); Group 4: administered AV 5 days before and 5 days after MTX. For the first time, this study affords evidence for AV's hepatoprotective effects on MTX-induced hepatotoxicity. The underlined mechanisms behind its hepatic protection include counteracting MTX-induced oxidative injury via down-regulation of NADPH oxidase and up-regulation of Nrf2/ARE, SIRT1, PPARγ, and cytoglobin signals. Additionally, AV attenuated hepatic inflammation through down-regulation of IL-6/STAT-3 and NF-κB/AP-1 signaling. Network pharmacology analysis exhibited a high enrichment score between the interacting proteins and strongly suggested the intricate and essential role of the target proteins regulating MTX-induced oxidative damage and inflammatory perturbation. Besides, AV increased the in vitro cytotoxic activity of MTX toward PC-3, HeLa, and K562 cancer cell lines. On the whole, our investigation suggested that AV might be regarded as a promising adjuvant for the amelioration of MTX hepatotoxicity and/or increased its in vitro antitumor efficacy, and it could be used in patients receiving MTX.

Brain-derived Neurotropic factor (BDNF) mediates the protective effect of Cucurbita pepo L. on salivary glands of rats exposed to chronic stress evident by structural, biochemical and molecular study.

BACKGROUND: Acute and chronic stresses affect the salivary glands, representing the source of plasma BDNF during stressful conditions. Pumpkin is a medicinal plant with an evident antioxidant, anti-inflammatory and potential antidepressant effects. OBJECTIVE: To assess the structural and biochemical effects induced by exposure to chronic unpredictable mild stress (CUMS) on salivary glands of albino rats, and to evaluate the role of pumpkin extract (Pump) in ameliorating this effect. METHODOLOGY: Four groups (n=10 each) of male albino rats were included in this study: the control, CUMS, Fluoxetine-treated and Pump-treated. The corticosterone, the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and the oxidant/antioxidant profile were all assessed in the serum. The level of BDNF mRNA was measured in the salivary glands using qRT-PCR. Histopathological changes of the salivary glands were also assessed. RESULTS: The depressive-like status was confirmed behaviorally and biochemically. Exposure to CUMS significantly up-regulated (p<0.001) the level of serum corticosterone. CUMS induced degenerative changes in the secretory and ductal elements of the salivary glands evident by increased apoptosis. Both Fluoxetine and Pumpkin significantly up-regulated (p<0.001) BDNF expression in the salivary glands and ameliorated the CUMS-induced histopathological and biochemical alterations in the salivary glands. Pumpkin significantly (p<0.001) increased the serum levels of antioxidant enzymes SOD, GPX and CAT, and reduced the serum levels of the pro-inflammatory cytokines TNF-α, IL-6. CONCLUSION: Pumpkin ameliorates the depressive-like status induced in rats following exposure to chronic stress through exerting a promising anti-inflammatory, antioxidant and anti-depressant-like effects. The pumpkin, subsequently, improved stress-induced structural changes in the salivary glands that might be due to up-regulation of BDNF expression in the glands.

Synergistic Anti-inflammatory and Neuroprotective Effects of Cinnamomum cassia and Zingiber officinale Alleviate Diabetes-Induced Hippocampal Changes in Male Albino Rats: Structural and Molecular Evidence.

Background: Depression has been reported as a common comorbidity in diabetes mellitus although the underlying mechanism responsible for this is not well known. Although both ginger and cinnamon has anti-diabetic, antioxidant, and neuroprotective properties, their efficacy in inhibiting neuroinflammation, when simultaneously administrated, has not been investigated yet. Objectives: The study was designed to assess the synergistic effect of Cinnamomum cassia and Zingiber officinale on regulating blood glucose, improve hippocampal structural changes and depressive-like alternations in diabetic rats, and try to identify the mechanism behind this effect. Materials and Methods: Thirty male Sprague-Dawley rats were divided into five equal groups (n = 6): the normal control, untreated streptozotocin (STZ)-diabetic, cinnamon-treated diabetic [100 mg/kg of body weight (BW)/day for 6 weeks], ginger-treated diabetic (0.5 g/kg BW/day for 6 weeks), and ginger plus cinnamon-treated diabetic groups. Forced swim test and elevated plus maze behavioral tests were performed at the end of the experiment. HOMA-IR, HOMA ß-cells, blood glucose, insulin, corticosterone, pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and IL-6), and total anti-oxidant capacity (TAC) were assessed in the serum. BDNF mRNA level was assessed in hippocampus using qRT-PCR. Hippocampal histopathological changes were also assessed, and immunoexpression of glial fibrillary acidic protein (GFAP), caspase-3, and Ki-67 was measured. Results: Diabetes-induced depressive-like changes in the STZ group were biochemically confirmed by assessing serum corticosterone level, as well as behaviorally using FST and EPM tests. Diabetes also induced degenerative changes in the hippocampus. Treatment of diabetic rats with ginger, cinnamon, or the combination of these alleviated the degenerative structural changes and significantly up-regulated serum insulin, TAC, hippocampal BDNF mRNA, and hippocampal immunoexpression of ki67, while they significantly reduced serum blood glucose, IL-6, TNF-α, IL1ß, as well as hippocampal immunoexpression of GFAP and Caspase-3 compared to the untreated diabetic group. Improvement induced by the combination of ginger and cinnamon was superior to the single administration of either of these. Conclusion: Cinnamomum cassia and Zingiber officinale have synergistic anti-diabetic, antioxidant, anti-inflammatory, antidepressant-like, and neuroprotective effects. The use of a combination of these plants could be beneficial as alternative or complementary supplements in managing DM and decreasing its neuronal and psychiatric complications.

Musk (Moschus moschiferus) Attenuates Changes in Main Olfactory Bulb of Depressed Mice: Behavioral, Biochemical, and Histopathological Evidence.

BACKGROUND: Musk (Moschus moschiferus) has been described to have a significant impact on the central nervous system, as well as anticonvulsion and antidepressant effects. This study was designed to evaluate the efficacy of musk in alleviating alterations induced in olfactory bulb of depressed mice exposed to chronic stress and identify the mechanism behind it. METHODS: Fifty male albino mice were divided into five groups (n = 10 each): control, musk, chronic unpredictable mild stress (CUMS), fluoxetine-treated, and musk-treated groups were included in this study. Behavioral changes and serum levels of corticosterone and proinflammatory cytokines included tumor necrosis factor α, interleukin 6, and oxidant/antioxidant profile were assessed at the end of the experiment. Main olfactory bulb (MOB) has been processed for histopathological examination. Gene expression of caspase-3, glial fibrillary acidic protein, and Ki67 were assessed in the MOB using quantitative real-time polymerase chain reaction. RESULTS: The study showed that musk inhalation significantly reduced (p < 0.001) corticosterone level, immobility time, inflammatory cytokines, and oxidative stress markers in CUMS-exposed mice compared to the untreated CUMS group. Musk lessened CUMS-associated neuronal alterations in the MOB and significantly reduced apoptosis and enhanced neural cell proliferation (p < 0.001) comparable to fluoxetine. Musk significantly enhanced the level of antioxidants in the serum and significantly reduced inflammatory cytokines. The anti-inflammatory and antioxidant activity of musk and its constituents seemed to be behind its neuroprotective effect observed in this study. CONCLUSION: Musk effectively ameliorated the chronic stress-induced behavioral, biochemical, and neuronal structural changes in MOB mostly through its antioxidant and anti-inflammatory effect.

Potential hepatoprotective effects of flavonoids contained in propolis from South Sulawesi against chemotherapy agents.

The use of doxorubicin and epirubicin as chemotherapy agent causes side effects such as liver damage due to oxidative stress by reactive oxygen species (ROS) that cause increased of ALT and AST level as liver parameter. One source of natural antioxidants as ROS neutralizer comes from flavonoid that contain in propolis. Most researchers claim that flavonoid can be used to protect the liver. The aim of this study was to test the hepatoprotective effect of flavonoid in propolis from South Sulawesi against doxorubicin and epirubicin. The experiment included male Sprague dawley rats divided into nine groups. The rats received the microcapsule propolis or the quercetin orally for 15 days. The hepatotoxicity was promoted by injection epirubicin and doxorubicin (i.v.) with a cumulative dose of 9 mg/kg. In this study, total polyphenol and flavonoid tests of propolis have been carried out, there were 1.1% polyphenols and 2.7% flavonoids, the antioxidant activity tests showed IC50 value of 9849 ppm and LCMS/MS tests supported the presence of phenolic compounds in propolis from South Sulawesi. Liver parameter was measured and the results showed that the propolis 200 mg/kg group produced the lowest ALT and had potential protective effect against doxorubicin and epirubicin-induced hepatotoxicity.