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Diabetes mellitus is a persistent metabolic condition marked by elevated blood glucose levels due to compromised insulin secretion or functionality. The search for natural antidiabetic agents has gained attention due to their potential effectiveness and safety profiles. Sessuvium portulacastrum, a coastal plant, has been traditionally used for various medicinal purposes. This study investigates the antidiabetic potential of Sessuvium portulacastrum aqueous extract by analyzing its inhibitory effects on key enzymes involved in carbohydrate metabolism and exploring its molecular interactions with critical target proteins. The aqueous extract of Sessuvium portulacastrum was prepared and used for in vitro analysis. The reduced activity of the extract against α-amylase and α-glucosidase enzymes, crucial in glucose absorption and postprandial hyperglycemia, was assessed. Molecular docking techniques were employed to explore the potential interactions between active compounds in the extract and diabetes-related proteins, including BAX, GSK3β, and CADH. The study revealed significant inhibition of both alpha-amylase and alpha-glucosidase enzymes by Sessuvium portulacastrum aqueous extract, indicating its potential to reduce glucose absorption and postprandial hyperglycemia. Moreover, the molecular docking analysis demonstrated strong binding interactions between active compounds in the extract and key proteins involved in diabetes-related pathways, namely apoptotic pathways, glycogen synthesis, and cell adhesion. The findings of this study highlight the promising antidiabetic potential of Sessuvium portulacastrum aqueous extract. Upcoming research should get an attention on isolating and characterizing the active compounds responsible for these effects on antidiabetic therapies from natural sources.

The current study aimed to investigate the sensitivity of male testis parenchyma cells to chemotherapy agents and the protective effects and mechanisms of Morinda citrifolia (Noni) administration against structural and functional changes before and after chemotherapy (Paclitaxel (PTX)). For this purpose, rats were randomly assigned into four groups (Control = G1, PTX 5 mg/kg = G2; PTX + Noni 10 mg/kg = G3, PTX + Noni 20 mg/kg = G4). PTX was injected intraperitoneally for 4 consecutive weeks, at a dose of 5 mg/kg to all groups except the control group. Then noni was administrated in 10 (G3) and 20 (G4) mg/kg groups orally (gavage) for 14 days. Biochemical analyses, Real-Time Polymerase Chain Reaction (PCR), and immunohistochemical analyses were performed. According to our results, Total Oxidative Stress (TOS) and Malondialdehyde (MDA) were significantly increased in the PTX group (P < 0.01). Superoxide Dismutase (SOD) enzyme activity and Total Antioxidant Capacity (TAC) levels were decreased (P < 0.01). The changes in the rats treated with PTX + Noni 20 mg/kg were noteworthy. The increased levels of IL1-β (Interleukin 1 beta) and TNFα (tumor necrosis factor-alpha) with PTX were down-regulated after treatment with PTX + Noni 20 mg/kg (P < 0.01) (9 % and 5 % respectively). In addition, Noni restored the testicular histopathological structure by reducing caspase-3 expression and significantly (61 %) suppressed oxidative DNA damage and apoptosis (by regulating the Bax (bcl-2-like protein 4)/Bcl-2 (B-cell lymphoma gene-2) ratio). In conclusion, Noni reduced cellular apoptosis and drastically changed Caspase 8 and Bax/Bcl-2 levels. Furthermore, it considerably decreases oxidative damage and can be used in testicular degeneration.

Traditional therapies often struggle with specificity and resistance in case of cancer treatments. It is therefore important to investigate new approaches for cancer treatment based on nanotechnology. Zinc oxide nanoparticles (ZnONPs) are known to exhibit anti-cancer properties by inducing oxidative stress, apoptosis, and cell cycle arrest. Methotrexate (MTX) a known anti-folate shows specificity to folate receptors and interrupts healthy functioning of cells. This study proposes the use of previously characterized biocompatible Methotrexate loaded Zinc oxide nanoparticles (MTX-ZnONPs) as a dual action therapeutic strategy against breast cancer cell lines, MCF-7 (MTX-sensitive) and MDA-MB-231 (MTX-resistant). To elucidate the cytotoxicity mechanism of MTX-ZnONPs an in depthIn vitrostudy was carried out.In vitroassays, including cell cycle analysis, apoptosis assay, and western blot analysis to study the protein expression were performed. Results of these assays, further supported the anti-cancer activity of MTX-ZnONPs showing apoptotic and necrotic activity in MCF-7 and MDA-MB-231 cell line respectively.In vivoacute oral toxicity study to identify the LD50in animals revealed no signs of toxicity and mortality up to 550 mg kg-1body weight of animal, significantly higher LD50values than anticipated therapeutic levels and safety of the synthesized nanosystem. The study concludes that MTX-ZnONPs exhibit anti-cancer potential against breast cancer cells offering a promising strategy for overcoming resistance.

Brain insulin resistance is linked to metabolic syndrome (MetS). A low-carbohydrate, high-fat (LCHF) diet has been proposed to have a protective effect. Therefore, this study aimed to investigate the brain insulin resistance markers in a rat animal model of MetS and the protective effects of the LCHF diet. Four groups of male rats (10/group) were created. Group I (Control) was fed a regular diet. Groups II-IV were injected with dexamethasone (DEX) to induce MetS. Group II received DEX with a regular diet. Group III (DEX + LCHF) rates were fed a low-carbohydrate, high-fat diet, while Group IV (DEX + HCLF) rats were fed a high-carbohydrate, low-fat (HCLF) diet. At the end of the four-week experiment, HOMA-IR was calculated. Moreover, cerebral gene expression analysis of S-100B, BDNF, TNF-α, IGF-1, IGF-1 R, IGFBP-2, IGFBP-5, Bax, Bcl-2, and caspase-3 was carried out. In the DEX group, rats showed a significant increase in the HOMA-IR and a decrease in the gene expression of IGF-1, IGF-1 R, IGFBP-2, IGFBP-5, BDNF, and Bcl2, with a concomitant rise in S100B, TNF-α, Bax, and caspase-3. The LCHF diet group showed a significantly opposite effect on all parameters. In conclusion, MetS is associated with dysregulated cerebral gene expression of BDNF, S100B, and TNF-α and disturbed IGF-1 signaling, with increased apoptosis and neuroinflammation. Moreover, the LCHF diet showed a protective effect, as evidenced by preservation of the investigated biochemical and molecular parameters.

The food color metanil yellow (Myl) is hazardous to several body systems. Evening primrose oil (EPO) was reported to have anti-inflammatory and anti-oxidant properties. The present work investigated the impact of Myl on the hepatic structure and function of rats and evaluated the protective effect of EPO. Forty adult male rats were divided into four groups: control, EPO (5 g/kg/day), Myl (200 mg/kg/day), and EPO- Myl group. Myl significantly increased liver enzymes, advanced glycation end products (AGE), oxidative stress parameters, pro-inflammatory cytokines, nuclear factor kappa B (NF-κB), and inducible nitric oxide synthase (iNOS). Blood vessels in the liver were dilated and congested, with cellular infiltration around them and associated with fibrosis. The hepatocytes were vacuolated and had dark nuclei. The immunohistochemical expression of iNOS, glial fibrillary acidic protein (GFAP), and Bax was significantly elevated. Ultrastructurally, the hepatocytes showed lipid droplets, irregular condensed nuclei with widened perinuclear space, dilated rER, mitochondria with destructed cristae, and multiple vacuoles. Dilated congested blood sinusoids and collagen fiber bundles were seen between hepatocytes. Interestingly, these alterations were less pronounced in rats co-administrated with EPO and Myl. In conclusion, EPO can protect liver against the toxic effects of Myl due to its anti-inflammatory and anti-oxidant activities.

lactoferrin (Lf) is a glycoprotein with various biological activities, including antibacterial, antiviral, anti-cancer, etc. In the present study, the effect of different concentrations of nano-encapsulated lactoferrin (NE-Lf) on the expression of Bax and Bak genes was evaluated in stomach cancer cell line AGS using real-time PCR technique and cytotoxicity of NE-Lf on the growth cells as well as the molecular mechanism of these two genes and their proteins in the apoptosis pathway and the relationship between lactoferrin and these proteins were investigated by bioinformatics studies. In the viability test, the results showed that the growth inhibition effect of nano-lactoferrin was greater than lactoferrin in both concentrations, and chitosan had no inhibitory effect on the cells. In concentrations of 250 and 500 µg of NE-Lf Bax gene expression increased by 2.3 and 5 times, respectively, and Bak gene expression increased by 1.94 and 1.74 times, respectively. Statistical analysis showed that there is a significant difference in the relative amount of gene expression between the treatments in both genes (P < 0.05). The binding mode of lactoferrin with Bax and Bak proteins was obtained using docking. According to docking results, the N-lobe region of lactoferrin interacts with the Bax protein, as well as the Bak protein. The results show that lactoferrin, in addition to acting on the gene, interacts with Bax and Bak proteins. Since two proteins are components of apoptosis, lactoferrin can induce apoptosis in this way.

It is a well-known fact that general anesthesia leads to cerebral hemorrhage in patients with spontaneous hypertension apart of the fact that the hypertension is under control. The literature is already flooded with this debate, and still, there appears a lag regarding the effects of high blood pressure on pathological changes in the brain after cerebral hemorrhage. They are still not well recognized. Furthermore, it is the stage of anesthesia resuscitation which is known to have adverse effects on the body during cerebral hemorrhage. Owing to the lag of knowledge in the above said facts, the objectives of this study were to evaluate the effects of propofol combined with sufentanil on the expression of Bax, BCL-2, and caspase-3 genes in spontaneously hypertensive rats suffering with cerebral hemorrhage. The initial sample consisted of 54 male Wrister rats. All were of the age of 7 to 8 months with a weight of 500 ± 100 gm. All the rats were evaluated by the investigators before enrolment. A total of 0.5 mg/kg ketamine followed by a 10 mg/kg intravenous injection of propofol was introduced to each included rat. It was followed by a total of 1 μG/kg/h of sufentanil which was administered to rats who had cerebral hemorrhage (n = 27). The rest 27 normal rats were not administered with sufentanil. Hemodynamic parameters, biochemistry, western blot assay, and immunohistochemical staining were performed. The results were statistically analyzed. Heart rate (p < 0.0001) was higher for rats who had a cerebral hemorrhage. The cytokine levels of rats who had cerebral hemorrhage were higher than those of normal rats (p < 0.01 for all). Bacl-2 (p < 0.01), bax (p < 0.01), and caspase-3 (p < 0.01) expressions were reported to be disturbed in rats who had cerebral hemorrhage. Urine volume was reduced in rats who had cerebral hemorrhage (p < 0.01). It was concluded that in spontaneously hypertensive rats with cerebral hemorrhage, propofol combined with sufentanil target-controlled intravenous anesthesia increased hemodynamic parameters and cytokine levels. Furthermore, cerebral hemorrhage disturbs the expression of bacl-2, Bax, and caspase-3 expressions.

Bovine gammaherpesvirus type 4 (BoHV-4) shows tropism for the endometrium, in which it causes the death of epithelial and stroma cells. Despite having anti-apoptotic genes in its genome, experiments based on immortalized cell lines have shown that BoHV-4 induces cell death by apoptosis. In the present study, we evaluated BoHV-4 replication, pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) mitochondrial genes expression and chromatin condensation in bovine endometrium primary culture cells (BEC) and in the Madin Darby bovine kidney (MDBK) cell line. Results showed that BoHV-4 has a preference for replication in BEC cells over the MDBK cell line, demonstrated by the high viral titer that is consistent with the tropism of the virus. In BEC cells, chromatin condensation was consistent with the values of viral kinetics at the late stage of infection, accompanied with a balance in the mRNA levels of apoptotic mitochondrial proteins. As a consequence, in those cells viral transmission would be enhanced by inhibiting apoptosis in the early stage of virus proliferation, allowing the complete production of viral progeny, and then, the induction of apoptosis in late stages would allow neighboring cells infection. In MDBK cells replication kinetics was coincident with the up-regulation of Bcl-2, which suggests that the productive infection in MDBK is associated with a lytic phase of the virus or another cell death pathway (probably autophagy mechanism) at the late stage of infection. The results agree with the study of nuclear morphology, where a constant chromatin condensation was observed over time. It is clear that the documented BoHV-4 apoptotic responses observed in the cell lines studied above are not valid in cells from primary cultures. The data presented in this study suggest that BoHV-4 could induce apoptosis in BEC cells without a leading role of the mitochondria pathway. Further studies will be necessary to characterize in detail the programmed cell death pathways involved in BoHV-4 infection in the primary cell cultures evaluated.

UNASSIGNED: This study aimed to investigate the expression of autophagy-related factors microtubule-associated protein l light chain 3 (LC3) and the apoptosis-related factors BCL2-associated X protein (Bax) and B cell lymphoma-2 (Bcl-2) in the periodontal tissue of experimental diabetic rats. These data were used to explore the potential mechanism in diabetes-induced periodontal tissue lesions.
UNASSIGNED: A total of 32 Sprague Dawley (SD) rats were randomly assigned into diabetes (group D, n = 16) and control groups (group N, n = 16). The diabetic group was induced by intraperitoneal injection of 1% streptozotocin (STZ, 60 mg/kg) and the control group was injected with citrate buffer (0.1mol/L). Rats were sacrificed after 4 and 8 weeks of feeding and collected as D1, N1 groups and D2, N2 groups, and the maxilla were retained for analysis. The changes in periodontal tissue structure were observed by hematoxylin-eosin (HE) staining. The expression and distribution of LC3, Bax and Bcl-2 in the periodontium of the rats was detected by immunohistochemical (SP) staining.
UNASSIGNED: Diabetic rats showed several changes compared to control animals including sparse alveolar bone trabecular structure, loss of the lamina dura and absorption of the local alveolar bone. The positive expression level of LC3 in the gingival epithelial, periodontal ligament and alveolar bone of group D1 was significantly higher than in the N1, N2 and D2 groups (P < 0.05). The level of Bax expression in the group D2 rats was significantly higher than those in the N1, N2 and D1 groups (P < 0.05), while the positive degree of Bcl-2 was significantly lower than those of other groups (P < 0.001). LC3 was negatively correlated with Bax and was irrelevant with Bcl-2; Bcl-2 was not correlated with Bax.
UNASSIGNED: The expression of LC3, Bax and Bcl-2 changes in the periodontal tissue of diabetic rats may indicate that autophagy and apoptotic are involved in the process of periodontal tissue damage in diabetic rats. These changes may be one of the mechanisms of periodontal tissue lesions.