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Increased visfatin expression has been shown to increase gene expression, which promotes cell survival and increases SirT1 activity thereby promoting angiogenesis. Previous studies have shown that oral squamous cell carcinomas (OSCCs) express high levels of activated signal transducer and activator of transcription 3 (Stat3). Since visfatin expression is increased by Stat3, we hypothesized that visfatin protein may be highly expressed in OSCCs. Immunohistochemistry was the technique used to examine the expression of visfatin in 19 OSCCs and 4 hyperplastic lesions. The results indicated that visfatin was detected in the cytoplasm and nuclei of the OSCCs and epithelial hyperplasia as well as in the stromal tissues of patients with OSCC and oral hyperplasia. Furthermore, co-expression of visfatin and proliferating cell nuclear antigen proteins was noted in verrucous epithelial hyperplasia, and co-expression of visfatin and CD68 in the inflammatory cells of the stromal region was noted in the OSCCs. In addition, enzyme-linked immunosorbent assay showed that plasma visfatin concentrations were significantly increased in the patients with OSCC and oral hyperplasia compared to those of the control subjects. In conclusion, visfatin expression and concentrations were higher in OSCCs and oral hyperplasia, suggesting that visfatin may play a role in the pathogenesis of oral cancers.

Cancer immunotherapy offers tremendous clinical outcomes in cancer management with the potential to induce sustained remission in patients with refractory disease. One of these immunotherapy modalities is the adoptive transfer of autologous T-cells that are genetically engineered ex vivo to express chimeric antigen receptors (CARs). These receptors can direct T-cells to the surface antigens of tumor cells to initiate an efficient and specific cytotoxic response against tumor cells. This review elucidates the structural features of CAR T-cells and their different generations reaching the recent 4th generation (TRUCK). The step-wise treatment process using CAR T-cell therapy and some of the updated prominent clinical applications of this treatment modality in both hematologic and solid malignancies are also covered in the present review. The success of CAR T-cell therapy is still encountered by several limitations for a widespread clinical application of this treatment modality, these challenges along with the recent innovative strategies that have been developed to overcome such drawbacks, as well as, the approaches and future directions aiming for a commercial low cost CAR T-cell immunotherapy modality, are all covered in the present review.

Embryonic stem (ES) cells are pluripotent cells widely used in cell therapy and tissue engineering. However, the broader clinical applications of ES cells are limited by their genomic instability and karyotypic abnormalities. Thus, understanding the mechanisms underlying ES cell karyotypic abnormalities is critical to optimizing their clinical use. In this study, we focused on proliferating human and mouse ES cells undergoing multipolar divisions. Specifically, we analyzed the frequency and outcomes of such divisions using a combination of time-lapse microscopy and cell tracking. This revealed that cells resulting from multipolar divisions were not only viable, but they also frequently underwent subsequent cell divisions. Our novel data also showed that in human and mouse ES cells, multipolar spindles allowed more robust escape from chromosome segregation control mechanisms than bipolar spindles. Considering the frequency of multipolar divisions in proliferating ES cells, it is conceivable that cell division errors underlie ES cell karyotypic instability.

Kidney and uropoetic system diseases represent a major social, economic and health burden. This is mainly because early diagnosis of kidney dysfunction is currently unavailable, since the current markers are often reliably increased only after advanced progression of the renal diseases. Recently, circulating nucleosomes, DNA and numerous forms of RNA have been detected in human biological fluids, such as plasma, urine, saliva, and breast milk. Although their biological functions remain mostly unknown, they are attractive as potential biomarkers of various diseases. In urine, many of the circulating nucleic acids originate from the cells of the kidney and the urinary tract making these non-invasive and easily obtained new biomarkers in the nephrology or urology. This review focuses on cell free nucleic acids in urine and its potential in human studies. Although, there are some technical and biological limitations, the urinary circulating nucleic acids hold a great potential as new biomarkers of renal diseases.

Oleanolic acid (OA) is a pentacyclic triterpenoid with favourable physiological activity. It is widely distributed in more than 200 species of plants. OA has garnered significant interest because of its potential biological activities, such as antioxidant, bacteriostatic, and hair growth-promoting effects. To study the effect of OA on hair growth and related mechanisms, we investigated hair growth in mice with testosterone-induced androgenetic alopecia (AGA) that were treated with three different concentrations of OA. The antioxidant, bacteriostatic, and cytotoxic effects of OA were evaluated. We found that mice with testosterone-induced AGA treated with 1% or 0.5% OA showed significantly enhanced hair growth and increased vascular endothelial growth factor/glyceraldehyde-3-phosphate dehydrogenase ratio and levels of fibroblast growth factor receptor and insulin-like growth factor 1. Using an immunofluorescence staining assay, we demonstrated that β-catenin, a key Wnt signalling transducer, was highly expressed in the OA-treated groups. These results suggest that OA may promote hair growth by stimulating hair matrix cell proliferation via the Wnt/β-catenin pathway and lowering the levels of tumour necrosis factor-alpha, and transforming growth factor-beta 1, dihydrotestosterone, and 5α-reductase.

Introduction: Thymoquinone (TQ) is one of the bioactive compounds in Nigella sativa (NS). Also known as black seeds/cumin, it has been postulated to possess anti-atherogenic properties. However, research on the effects of NS oil (NSO) and TQ on atherogenesis remain scarce. The aim of this study is to determine gene and protein expression of Intercellular Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), and Endothelial-eukocyte adhesion molecule (E-selectin) in Human Coronary Artery Endothelial Cells (HCAECs). Methods: HCAECs were stimulated for 24 hours (h) with 200 µg/ml of Lipopolysaccharides (LPS) and different concentrations of NSO (55, 110, 220, 440 µg/ml) or TQ (4.5, 9.0, 18.0, 36.0 µm). The effects of NSO and TQ on gene and protein expressions were measured using multiplex gene assay and ELISA assay, respectively. Rose Bengal assay was used to analyse monocyte binding activity. Results: NSO and TQ significantly reduced ICAM-1 and VCAM-1 gene and protein expressions. TQ showed significant reduction activity of the biomarkers in dose dependent manner. HCAECs pre-treated with NSO and TQ for 24 h significantly lowered monocytes adherence compared to non-treated HCAECs. Conclusions: NSO and TQ supplementation have anti-atherogenic properties and inhibit monocytes' adherence to HCAECs via down-regulation of ICAM-1 expression. NSO could potentially be incorporated in standard treatment regimens to prevent atherosclerosis and its related complications.

Myocardial hypertrophy may lead to heart failure and sudden death. As traditional Chinese medicine, Guanxinning tablets (GXN) have significant pharmacological effects in the prevention and treatment of cardiovascular diseases. However, the anti-cardiac hypertrophy efficacy of GXN and its mechanism of action are still unclear. Therefore, we established a heart failure rat model and isolated primary cardiomyocytes of neonatal rat to observe the protective effect of GXN on heart failure rat model and the intervention effect on myocardial cell hypertrophy, and to explore the possible mechanism of GXN preventing and treating myocardial hypertrophy. The results of in vivo experiments showed that GXN could significantly reduce the degree of cardiac hypertrophy, reduce the size of cardiomyocytes, inhibit the degree of myocardial remodeling and fibrosis, and improve cardiac function in rats with early heart failure. The results of in vitro experiments showed that GXN was safe for primary cardiomyocytes and could improve cardiomyocyte hypertrophy and reduce the apoptosis of cardiomyocytes in pathological state, which may be related to the inhibition of the over-activation of MEK-ERK1/2 signaling pathway. In conclusion, GXN may inhibit cardiac hypertrophy and improve early heart failure by inhibiting the over-activation of MEK-ERK1/2 signaling pathway.

Introduction: This study aimed to identify the phytochemical constituents that could target gastric cancer in Kangai injection using a network pharmacology-based approach. Methods: Protein-protein interactions (PPI), Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted utilizing String and OmicShare tools. In the in vitro experiments, the related mRNA and protein levels were assessed via real-time quantitative polymerase chain reaction and Western blotting, respectively. Cell proliferation was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Results: Kangai injection comprises several compounds, which target multiple substrates and pathways related to gastric cancer. The PPI and Gene Ontology analyses revealed that tumor necrosis factor (TNF) was a hub gene. KEGG pathway enrichment analysis indicated that the the TNF pathway was significantly enriched. Kangai injection decreased the mRNA levels of TNFR2, TRAF2, PI3K, AKT, and IκBα and inhibited the phosphorylation of PI3K, AKT, and IκBα phosphorylations. Kangai injection inhibited cell proliferation, while TNFR2 overexpression or treatment with the PI3K activator 740 Y-P partially restored it. Conclusion: Kangai injection operates through multiple targets and pathways in gastric cancer, with the TNFR2/PI3K/AKT/NF-κB pathway playing a crucial role in its mechanism against gastric cancer.

Background: Ginsenoside Rb2 is beneficial in cardiovascular disease treatment, yet its role in heart failure (HF) is obscure. This study aimed to investigate the effect and mechanism of ginsenoside Rb2 on HF. Methods: The left anterior descending branch-ligated HF rat model and oxygen-glucose deprivation/reoxygenation (OGD/R) H9c2 cell model were constructed. Ginsenoside Rb2 were applied for intervention. Heart function indexes, miR-216a-5p expression, autophagy, oxidative stress, apoptosis, cell morphology, and proliferation were detected to explore the effect of ginsenoside Rb2 on HF. Overexpression of miR-216a-5p was employed to explore the specific mechanism of ginsenoside Rb2 on HF. Results: Ginsenoside Rb2 improved the heart function of HF rats, including the reduction of heart rate, LVEDP, and heart weight/body weight ratio, and the increase of LVSP, +dP/dtmax, -dP/dtmax, LVEF, and LVFS. It also down-regulated miR-216a-5p expression and enhanced OGD/R-induced cardiomyocyte viability. Ginsenoside Rb2 up-regulated Bcl2, LC3B II/I, and Beclin1, and down-regulated Bax, Caspase-3, and p62 in the myocardium of HF rats and OGD/R-induced H9c2 cells. Moreover, ginsenoside Rb2 increased the levels of SOD and CAT, but decreased the levels of MDA and ROS in the myocardium of HF rats and OGD/R-induced H9c2 cells. However, overexpression of miR-216a-5p promoted the apoptosis and oxidative stress of cardiomyocytes and inhibited autophagy, thus reversing the therapeutic effect of ginsenoside Rb2 on HF in vivo and in vitro. Conclusion: Ginsenoside Rb2 demonstrated potential as a therapeutic intervention for HF by enhancing autophagy and reducing apoptosis and oxidative stress through miR-216a-5p downregulation. Further research could explore its application in clinical trials and investigate the complex mechanism networks underlying its effects.

The role of oxidants and proinflammatory cytokines in the pathogenesis of pneumonia caused by Staphylococcus aureus (S. aureus) has been demonstrated. The present study aims to investigate the protective effect of ethyl acetate extract (EtOAc) obtained from Usnea longissima (UL) against acute oxidative and inflammatory lung damage due to S. aureus infection in rats. Albino Wistar-type male rats were divided into three groups: Healthy (HG), S. aureus inoculated (SaG), and S. aureus inoculated + ULEtOAc administered (SUL). SaG (n = 6) and SUL (n = 6) group rats' left nostrils (excluding HG) were inoculated with 0.1 ml bacterial mixture. After 24 hours, ULEtOAc (50 mg/kg) was administered orally to the SUL group, and the same volume of normal saline was administered orally to the HG (n = 6) and SaG groups. This procedure was performed once a day for seven days. Levels of oxidant and antioxidant parameters such as malondialdehyde (MDA) and total glutathione (tGSH), as well as pro-inflammatory cytokine levels such as nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-one beta (IL-1β), were measured in removed lung tissues. Tissues were also examined histopathologically. Biochemical results showed that ULEtOAc significantly suppressed the increase of MDA, NF-κB, TNF-α, and IL-1β levels and the decrease of tGSH caused by S. aureus in lung tissue. S. aureus inoculation caused severe mononuclear cell infiltration in interstitial areas, severe lymphoid hyperplasia in bronchial-associated lymphoid tissue and severe alveolar edema, histopathologically. Treatment with ULEtOAc had an attenuating effect on these histopathological findings. Experimental results from this study suggest that ULEtOAc may be beneficial in treating S. aureus-induced oxidative and inflammatory lung damage.

The aim of this study was to investigate the protective effect of naringenin on oxidative stress, on pro-inflammatory cytokines like TGF-β1, IL-1β and on programmed cell death in the testicular damage resulting from streptozotocin (STZ) induced diabetes in rats. Diabetes was induced by a single intraperitoneal injection of STZ (50 mg/kg), and the rats were treated with naringenin (5 mg/kg and 10 mg/kg) administered once a day orally for 10 weeks, starting 3 days after the STZ injection. At the end of the study, all animals were sacrificed. Testis tissue and blood samples were collected for the assessment of sperm parameters, and for biochemical and histopathological analysis. Naringenin treatment significantly decreased the levels of elevated tissue TBARS (thio-barbituric acid) and increased the superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) enzyme activities in the testis tissues. The naringenin-treated rats in the diabetic group showed an improved histological appearance, sperm parameters, and serum testosterone levels, along with a decrement of terminal dUTP nick end-labeling (TUNEL) detected program cell death and a reduced over expression of TGF-β1, IL-1β in Sertoli cells and Leydig cells. These results suggest that naringenin is a food supplement potentially beneficial in reducing testicular damage in diabetic rats by decreasing the oxidative stress related to programmed cell death.

Toxoplasma gondii, an etiologic agent of toxoplasmosis, is an obligate intracellular parasite, which exhibits an apicoplast organelle which assists in the metabolism of isoprenoids and other pivotal mediators for the parasite survival. Statins are drugs that inhibit cholesterol synthesis, blocking the conversion of the substrate HMG-CoA to mevalonate, thus preventing the initial processes of the biosynthesis of these precursors, both in humans and parasite. In the light of this information, we determined the effect of pravastatin and simvastatin associated with the current drugs (pyrimethamine and sulfadiazine) as a possible alternative treatment for this infection. Cytotoxicity was evaluated in HeLa cells by MTT assay, which was observed the drug combinations did not affect cell viability. HeLa cells (10⁵) were infected with T. gondii tachyzoites of RH strain (5 × 10⁵) and treated with pravastatin and/or simvastatin combined with pyrimethamine and/or sulfadiazine for 24 h. Our data showed a significant reduction in cell adhesion, infection and mainly parasite proliferation in all treatments. Based on these results, the combination of statins with drugs used in current therapy showed to be a promising therapeutic alternative for toxoplasmosis treatment.

Introduction
As a commonly used chemotherapeutic agent, fluorouracil (5-FU) has serious dose-limiting side effects. In this study, we evaluated the synergy between red American ginseng (RAG) and 5-FU on human colorectal cancer cells, and explored the potential mechanisms.
Methods
Ginsenoside contents of white American ginseng (WAG) and RAG were determined by HPLC. Cell proliferation was evaluated by MTS assay. Combination Index (CI) analysis was executed using CompuSyn software. Paraptotic events were observed after crystal violet staining. Cell cycle distribution, cyclin A expression and apoptotic induction were analyzed using flow cytometry.
Results
We observed the heat treatment remarkably increased levels of ginsenoside Rg3, 20R-Rg3, Rk1 and Rg5. When the combinations of 5-FU and RAG were applied, cell proliferation inhibition rates were notably increased, indicating that RAG significantly enhanced 5-FU's effect. Additionally, CI analysis suggested that there was a synergistic action of 5-FU and RAG when combined. The cell cycle data indicated 5-FU induced S phase arrest, and the combination of 5-FU and RAG increased G1 phase. Further, the RAG's ability to enhance the anti-cancer effects of 5-FU was linked to both paraptosis and apoptosis inductions.
Conclusion
RAG may have clinical utility to decrease the dosage of 5-FU in colorectal cancer therapeutics.

The natural products and conventional chemotherapeutic drugs combination can increase the efficacy of anticancer treatment through their potential synergistic effects and reduce its toxicity. The current study investigates the effect of methanolic extract from aerial parts of Juniperus excelsa on cell death activities induced by vincristine in acute lymphoblastic leukemia cells.
Cytotoxic activity of J. excelsa extract and vincristine in Nalm-6 and Reh cells was determined using MTT assay and synergism was evaluated using the CompuSyn software. Apoptosis was assessed by caspase 3 activity assay and flow cytometry. The expression levels of some apoptosis-related genes, Caspase 3, BAX and BCL-2 were determined by Real-time PCR. Statistical analysis was assessed by one-way ANOVA and Tukey's tests.
The combined treatment of VCR and J. excelsa extract showed a synergistic cytotoxic effect on both Nalm-6 and Reh cells at low doses of vincristine (CI < 1). J. excelsa extract also significantly increased VCR-induced apoptosis (P < 0.001). Expression of CASP3 and BAX genes were upregulated, while BCL-2 gene was downregulated in both cells (P < 0.05).
Our study suggested the combined use of lower doses of VCR and J. excelsa extract promote its effects by apoptosis induction and this combination could potentially decrease the side effects of the drug.

Introduction: Cancer stem cells (CSCs) are a theorized subset of cells within the tumor that is thought to drive disease recurrence and metastatic spread. The aim of this study is to investigate mRNA and protein levels of ganglioside GD2 synthase (GD2S), in breast cancer (BC) patients. Methods: 65 PBMCs of preoperative BC patients without chemotherapy were compared to PBMCs after chemotherapy and controls. Results: GD2S were significantly higher in BC patients after chemotherapy compared to pre-chemotherapy at both mRNA and protein. GD2S was higher in pre-chemotherapy blood samples compared to control samples. Conclusions: Higher expression of GD2S in BC samples compared to healthy control indicates the potential utility of GD2S as a marker of malignancy.

Context and objective: Zerumbone has been reported to exert anti-microbial effects, but the mechanism by which the compound exerts its action is not known. Thus, this study aimed to investigate the mechanism of action of zerumbone against methicillin-resistance Staphylococcus aureus (MRSA), using the atomic force microscopy (AFM), scanning electron microscopy (SEM), and flow cytometry techniques. Methods: MRSA (NCTC 13277) cell viability was determined using the microplate AlamarBlue assay. AFM and SEM were used to determine the morphology of zerumbone-treated MRSA cells. Flow cytometric analysis was used to determine the effect of zerumbone on bacterial membrane permeability and membrane potential, using the propidium iodide (PI) staining method, membrane potential-sensitive fluorescence probe, and DiBAC4(3) dye. DCFDA dye was used to determine the generation of reactive oxygen species (ROS) by MRSA. Results: Zerumbone significantly inhibited MRSA growth with a minimum inhibitory concentration (MIC) of 125 µg/ml. The AFM analysis showed that zerumbone caused leakage of cytoplasmic content from the bacterial cells. Ultrastructure analysis showed small colonies of the bacteria with pores on the membrane surface. There were increases in zerumbone-treated MRSA PI and DiBAC4(3) fluorescence, indicating an increase in cell membrane permeability and a decrease in membrane potential that culminated in the loss of membrane structural integrity and bacterial death. Based on DCFDA dye analysis, zerumbone also reduced ROS production by MRSA. Conclusions: Zerumbone exerts anti-MRSA effects by causing membrane depolarization, increasing membrane permeability, and finally disrupting cell membrane and bacterial killing.

Breast cancer is a serious public problem in modern society. Photodynamic therapy (PDT) is increasingly used in modern medicine. Currently, PDT is an innovative method of treating breast cancer. Irreversible damage to neoplastic tissues is associated with the use of physicochemical processes. Generating cytotoxic reactive oxygen species [singlet oxygen (1O2)] is leading to tumor cell death. At the same time, valuable information can be extracted from breast cancer cells. Photogenerated 1O2 is the major factor responsible for cell necrosis during PDT. 1O2 can react rapidly intracellularly with all organic substances. The use of photodynamic therapy on tissues in vitro creates conditions for testing various types of solutions and implementing them in in vivo treatment. This article is a review of recent advances in PDT for treatment of breast cancer. PDT is a novel cancer diagnostic and cancer treatment therapy. Therefore, an understanding of the possibility to generate a toxic form of 1O2 is necessary. The knowledge gained from the basics of PDT in vitro can be useful in biomedical applications in vivo. The current literature mentions PDT in the treatment of cancers located very deep within the human body. Therefore, the development of agents used to deliver 1O2 to the deep cancerous tissue is a new challenge which can have an efficient impact on this discipline. This review covers the literature between 2000-2022.

Statins are primary drugs in the treatment of hyperlipidemias. This group of drugs is known for its beneficial pleiotropic effects (e.g., reduction of inflammatory state). However, a growing body of evidence suggests its diabetogenic properties. The culpable mechanism is not completely understood and might be related to the damage to pancreatic beta cells. Therefore, we conceived an in vitro study to explore the impact of atorvastatin on pancreatic islet beta cells line (1.1.E7). We evaluated the influence on viability, insulin, low-density lipoprotein (LDL) receptor, and proprotein convertase subtilisin/kexin type 9 (PCSK9) expression. A significant drop in mRNA for proinsulin and insulin expression was noted. Concurrently, a rise in LDL receptor at the protein level in cells exposed to atorvastatin was noted. Further experiments have shown that exenatide - belonging to glucagon-like peptide 1 (GLP-1) analogs that are used in a treatment of diabetes and known for its weight reducing properties - can alleviate the observed alterations. In this case, the mechanism of action of exenatide was dependent on a protein kinase A pathway. In conclusion, our results support the hypothesis that statin may have diabetogenic properties, which according to our study is related to reduced insulin expression. The concomitant use of GLP-1 receptor agonist seemed to successfully revert insulin expression.

Periodontal regenerative techniques are performed to accomplish the restitution of soft and hard teeth-supporting tissues that have been lost due to trauma or inflammatory disease. Periodontal membranes are used for these techniques to provide support and a framework for cell growth and tissue regeneration. They act as a temporary and selective barrier to cell proliferation. Easy clinical handling, biomechanical specifications, high biocompatibility, cell-occlusivity, and satisfactory bioresorption rate are essential properties a membrane needs to be effective. The creation and maintenance of a secluded space is also a fundamental rule in periodontal regenerative techniques. The use of barrier membranes in the field of restorative dentistry has progressed toward the use of minimally invasive approaches optimizing wound closure and limiting patient morbidity. This review intends to provide an overview of the major cellular events in the surgical wound and membrane surface. It was also performed to assess, from literature data, the pertinence of using non-resorbable and resorbable membranes for this regenerative purpose. Special attention will be given to collagen membranes.

Telomeres are repetitive DNA located at the ends of chromosomes that preserve genomic stability. Excessive leukocyte telomere shortening is associated with cardio-metabolic disease and increased mortality risk. Although most studies indicate exercise training could attenuate leukocyte telomere attrition, data is somewhat equivocal. The inconsistencies could be partly explained by the different populations of leukocytes isolated for telomere length assessment. Accordingly, average peripheral blood mononuclear cell (PBMC) and whole blood leukocyte telomere length were assessed in 44 endurance athletes and 40 healthy controls using quantitative PCR. While whole blood leukocyte telomeres were, on average, 6.1% longer in endurance athletes compared to controls, PBMC telomere length was similar between the two cohorts in age and sex-adjusted analyses (athletes vs controls, mean T/S ratio ± SE: 3.25 ± 0.05 vs 3.23 ± 0.05, p = 0.72). Other than a weak inverse correlation with sitting (r = -0.25, p = 0.03), no statistically significant correlations were found between PBMC telomere length and exercise parameters. Unlike whole blood leukocytes, PBMC telomere length is not associated with endurance exercise and exercise parameters. These findings suggest the need for future work to quantify short and long telomeres of sorted immune cell populations and to measure them in context with cell counts and exercise traits.

The aim of this study was to investigate the occurrence of toxic effects in liver tissue of rats treated with α-terpinene. All treatments were intraperitoneally administered at doses of 0.5, 0.75 and 1.0 ml kg^-1 during 10 days. Liver samples were collected and assessed by histopathological analysis, caspases -1, -3, -8 assay, biomarkers of hepatic damage and determination of oxidant/antioxidant status (thiobarbituric acid-reactive substances (TBARS), catalase (CAT), superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione S-transferase (GST) and glutathione peroxidase (GPx)). Additionally, the cytotoxic and genotoxic effects were evaluated by comet assay. An increase was observed on TBARS levels and GPx activity on the hepatic tissue. Instead, CAT and SOD activities decreased in rats treated with a dose of 1.0 ml kg^-1 of α-terpinene. Concomitantly, ROS levels increased and GST levels decreased in rats treated with α-terpinene at doses of 0.5, 0.75 and 1.0 ml kg^-1. Also, there was an increase in frequency of damage, damage index and caspases, while cell viability decreased in rats treated with α-terpinene. Alanine aminotransferase and aspartate aminotransferase increased in rats treated with 1.0 ml kg^-1 of α-terpinene. Therefore, α-terpinene induces oxidative stress, cytotoxic and genotoxic effects in liver tissue involving the caspases activation.

Alnus japonica has been used as a traditional oriental medicine for many diseases such as fever, haemorrhage and alcoholism. In this study, A. japonica extracts were evaluated for their in vitro antioxidant potentials and anticancer effects in AGS human gastric carcinoma cell line. The antioxidant properties of A. japonica extracts were evaluated using several biochemical assays, including FRAP (ferric reducing antioxidant power) assay, ABTS (2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid)), DPPH (2,2-diphenyl-1-picrylhydrazyl), alkyl and hydroxyl radical scavenging activity assay. Our study showed that ethanol extract of A. japonica (AJE) has a more potent antioxidant activity than its water extract. In addition, AJE extract inhibited the cell growth and induced the cell death by increasing reactive oxygen species (ROS) production in AGS cells. Moreover, AJE extract specifically triggered the apoptosis mediated through the activation of caspase-8, 7, 3, and poly-ADP ribose polymerase (PARP). Thus, these results suggest that AJE extract could be potentially useful as a new promising strategy in the therapy for gastric carcinoma cancer.

Since last decade, biogenic synthesis of metal or metal-oxide nanoparticles is emerging as an alternative method, which is environment friendly, simple and safe to use. In this article, fruit waste (peel) extract (FWE) of three citrus fruits viz. Citrus limon, Citrus sinensis, and Citrus limetta were used as bio-reductant for green and sustainable synthesis of silver nanoparticles (AgNPs). As-synthesised AgNPs were characterized by using UV-vis spectroscopy, Dynamic light scattering, and High Resolution Transmission Electron Microscopy. TEM studies revealed 9-46 nm size range of synthesized AgNPs. The antimicrobial and antioxidant activities were also studied by using Agar well diffusion method and DPPH Assay, respectively. Nanoparticles showed good antimicrobial activity against both Gram positive (S. aureus) and Gram negative (E. coli) bacteria. Further, bioactivity assays revealed selective cytotoxicity (anticancer) of the nanoparticles against human lung cancer cell line A549. The nanoparticles are able to induce cancer cell specific apoptosis at G0/G1 phase of cell cycle. The results showed potential mechanism of action of nanoparticles via augmentation of antioxidant system in cancer cells. Over all, this study show multifaceted potential bioactivities of nanoparticles generated from fruit waste.

Isolation of unexplored frontier molecules are needed to treat multidrug resistant pathogens especially Methicillin resistant Staphylococcus aureus (MRSA). A marine sponge endosymbiotic Streptomyces albus ICN33 produces an anti-MRSA metabolite is reported. The crude extract exhibited anti-MRSA activity and the active principle was isolated through fermentation and chromatographic techniques. A compound PVI331 with a molecular mass of 506 Da have been determined by high resolution mass spectrometry. LC-MS based dereplication analysis had revealed that the detected compound PVI331 as unknown. The antibacterial assay of the compound PVI331 showed remarkable antagonistic activity against MRSA and Escherichia coli. Minimum inhibitory concentrations were found to be 1 μg/ml against MRSA. Sub-inhibitory concentration of the compound PVI331 reduced the biofilm formation of Staphylococcus aureus ATCC25923 and increased the cell surface hydrophobicity index. Scanning electron microscopic observation of the sub-inhibitory concentration exposure revealed a wrinkled membrane surface and slight cellular damage shows the cell wall distracting property of the compound. Zebrafish embryo based toxicity assays exhibited 48 ± 2 μg/ml of LC₅₀ value and 30 μg/ml of compound as maximal non-lethal concentration which had demonstrated the positive relationship in safety index. This study highlighted the anti-MRSA property of Streptomyces albus ICN33 from a marine sponge.

Resveratrol (RESV), an anticancer nutraceutical compound, is known to show poor bioavailability inside the human body. Therefore, this study has designed multiple chemical analogs of RESV compound for improving its pharmacokinetic as well as its anti-cancer properties. Initially, the drug likeliness and ADME-toxicity properties of these new chemical analogs were tested with the help of diverse computational approaches. Then the best predicted RESV derivative is synthesized by the organic method, and its NF-κB mediated anti-tumor activity assessed on histiocytic lymphoma U-937 cells. The new synthetic RESV analog, i.e. (E)-3-(prop-2-yn-1-yloxy)-5-(4-(prop-2-yn-1-yloxy) styryl) phenol has shown a rapid, persistent and better dose-dependent (IC50 of 7.25 μM) decrease in the viability of U937 cells than the native (IC50 of 30 μM) RESV compound. This analog has also demonstrated its potential ability in inducing apoptosis through DNA ladder formation. At 10 µg/ml concentration, this chemical derivative has shown a better NF-κB inhibition (IC50 is 2.45) compared to the native RESV compound (IC50 is 1.95). Molecular docking analysis found that this analog exerts its anti- NF-κB activity (binding energy of -6.78 kcal/mol and Ki 10 µM) by interacting with DNA binding residues (Arg246, Lys444, and Gln606) of p50 chain NF-κB. This study presents a novel RESV analog that could further develop as a potential anti-NF-κB mediated tumor inhibitor.

Inflammatory imbalance of bone formation/resorption leads to alveolar bone destruction. Astragalus polysaccharide has been confirmed to have anti-inflammatory effects. We sought to disclose the protective effect and its potential mechanisms of astragalus polysaccharide in the periodontitis model. Experimental periodontitis was induced by cotton ligatures for this study. We measured the alveolar bone damage rate, periodontal osteoclasts, proportion of CD4+Foxp3+, CD4+IL-10+, CD4+TGF-β+ subsets in the gingiva, and RANKL, OPG, TGF-β+, and IL-10+ level in the gingiva. We also cultured osteoclast precursor cells in the presence of RANKL and astragalus polysaccharide. Osteoclasto-like cells were identified by TRAP staining, mRNA of RANK, TRAP, and TRAF6 were evaluated by real time PCR. We found that astragalus polysaccharide caused significant protection of the alveolar bone via reducing local osteoclasts. It also decreased the proportion of CD4+Foxp3+ cells and upregulated the level of CD4+IL-10+ cells, reduced RANKL, and remedied IL-10 levels. In cell culture experiments, astragalus polysaccharide prohibited the RANKL mediated osteoclast differentiation. The findings of this study disclose the functions and possible mechanisms of astragalus polysaccharide engaged in local osteoclastogenesis, and reveal the considerable effect of astragalus polysaccharide in alveolar bone homeostasis and its likely contribution to host immuno-regulation in periodontitis.

Myricetin (MYR) and dihydromyricetin (DHM) are classified as natural flavonoids. Both substances are known for their anti-inflammatory and antioxidant properties. In this study, an in vitro model of inflammation was demonstrated on monolayers of scratched fibroblasts or keratinocytes exposed to LPS from Pseudomonas aeruginosa for six hours. MYR and DHM were subsequently applied to the cells for 24 hours at sub toxic concentrations (5-15 µM). Inflammatory parameters were analysed in collected cell medium and lysate after the incubation period using the Enzyme-Linked ImmuneSorbent Assay (ELISA) and Western blot. Both flavonoids inhibit the production of pro-inflammatory cytokines (IL-6, IL-8) in LPS-stimulated skin cells as well as the decreased level of MMP-1 in fibroblasts. However, the application of MYR and DHM dose dependently increased the level of MMP-1 in keratinocytes. In our experiments, we focused on the anti-glycation activity of MYR and DHM, where the higher concentration of MYR seems to be more effective.

AMP-activated protein kinase (AMPK) signaling shows an important role in energy metabolism and has recently been involved in osteogenic and adipogenic differentiation. In this study we aimed to investigate the role of AMPK activator, A-769662, in regulating the differentiation of mesenchymal stem cells derived from bone marrow (BMSCs) into osteoblastic and adipocytic cell lineage. The effect of A-769662 on osteogenesis was assessed by quantitative alkaline phosphatase (ALP) activity, matrix mineralization stained with Alizarin red, and gene expression analysis by quantitative polymerase chain reaction (qPCR). Adipogenesis was determined by Oil Red O staining for fat droplets and qPCR analysis of adipogenic markers. A-769662 activated the phosphorylation of AMPKα1 during the osteogenesis of mBMSCs as revealed by western blot analysis. A-769662 promoted the early stage of the commitment of mouse (m) BMSCs differentiation into osteoblasts, while inhibiting their differentiation into adipocytes in a dose-dependent manner. The effects of A-769662 on stimulating osteogenesis and inhibiting adipogenesis of mBMSCs were significantly eliminated in the presence of either AMPKα1 siRNA or Compound C, an inhibitor of AMPK pathway. In conclusion, we identified A-769662 as a new compound that promotes the commitment of BMSCs into osteoblasts versus adipocytes via AMPK-dependent mechanism. Thus our data show A-769662 as a potential osteo-anabolic drug for treatment of osteoporosis.

To investigate the association between inflammatory biomarkers and overt hypothyroidism (OH). We measured inflammatory cytokines, interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) as well as cell-free DNA (cf-DNA) levels in 40 OH patients and 40 healthy controls. Total cholesterol, high and low density lipoprotein subfractions, triglyceride, fibrinogen, and D-dimer were recorded. Increased inflammatory profile was evidenced through significant elevations in the concentrations of all cytokines and cf-DNA levels in the OH group. Lipids and prothrombotic markers were also increased in hypothyroid subjects. A significant association between the inflammatory cytokines and lipid profile was observed. A multivariate analysis showed that this result was independent of the sex, age and BMI status of the subjects. Hypothyroidism is associated with proinflammatory state. Lipid abnormalities have a stronger influence on inflammation, increasing cardiovascular risk and atherosclerosis development in hypothyroidism.

Alzheimer's disease (AD) threatens to become the scourge of the 21st century, hence there is an urgent need for the exploration of multipotent drug in the treatment of AD. Rhizophora mucronata, tropical red mangrove has been widely used in traditional oriental medicine as astringent, antiseptic, antibacterial, anti-ulcerogenic and anti-inflammatory agent. The present study aimed to evaluate the neuroprotective effect of the catechin rich methanolic leaf extract of R. mucronata (MERM), against Aβ-induced neurotoxicity. Exposure of PC12 cells to Aβ (25-35) increased cellular oxidative stress, the number of apoptotic cells and caspase-3 activity ultimately leading to neuronal death. Pre-treatment with MERM (50 μg/ml) significantly attenuated cell death, decreased the level of intracellular reactive oxygen and nitrogen species thereby inhibiting lipid peroxidation and protein oxidation. MERM attenuated Aβ (25-35) induced apoptosis by stabilizing the mitochondrial membrane potential, and inhibiting caspase-3 activity. MERM also restored the antioxidant status of the Aβ (25-35) treated cells by effectively scavenging ROS/RNS species. HPTLC analysis of MERM illustrated the presence of (+)-catechin as major constituent. Results conclude that MERM effectively attenuated the neurotoxicity induced by Aβ-associated oxidative stress, implying that MERM can act as a potent drug for the treatment of AD.