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Alcohol consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Diosmin (DIO) is a natural citrus flavone with remarkable antioxidant and anti-inflammatory features that underlay its protection against cardiac, hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus, the current study aimed to investigate the potential protective effects of DIO against ethanol-induced gastric injury in rats. Pretreatment with DIO (100 mg/kg p.o.) attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of ulcer index (UI) scores, area of gastric lesions, histopathologic aberrations and leukocyte invasion. These actions were analogous to those exerted by the reference antiulcer sucralfate. DIO suppressed gastric inflammation by curbing of myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) levels along with nuclear factor kappa B (NF-κB) p65 expression. It also augmented the anti-inflammatory interleukin-10 (IL-10) levels. Meanwhile, DIO halted gastric oxidative stress via inhibition of lipid peroxides with concomitant enhancement of glutathione (GSH), glutathione peroxidase (GPx) and the total antioxidant capacity (TAC). With respect to gastric mucosal apoptosis, DIO suppressed caspase-3 activity and cytochrome C (Cyt C) with enhancement of the anti-apoptotic B cell lymphoma-2 (Bcl-2) in favor of cell survival. These favorable actions were associated with upregulation of the gastric cytoprotective prostaglandin E2 (PGE2) and nitric oxide (NO). Together, these findings accentuate the gastroprotective actions of DIO in ethanol gastric injury which were mediated via concerted multi-pronged actions, including suppression of gastric inflammation, oxidative stress and apoptosis besides boosting of the antioxidant and the cytoprotective defenses.

Despite its broad applications, cisplatin affords considerable nephro- and hepatotoxicity through triggering inflammatory and oxidative stress cascades. The aim of the current investigation was to study the possible protective effects of tangeretin on cisplatin-induced hepatotoxicity. The impact of tangeretin on cisplatin-evoked hepatic dysfunction and histopathologic changes along with oxidative stress, inflammatory and apoptotic biomarkers were investigated compared to silymarin. Tangeretin pre-treatment significantly improved liver function tests (ALT and AST), inhibited cisplatin-induced lipid profile aberrations (total cholesterol and triglycerides) and diminished histopathologic structural damage in liver tissues. Tangeretin also attenuated cisplatin-induced hepatic inflammatory events as indicated by suppression of tumor necrosis factor-α (TNF-α) and enhancement of interleukin-10 (IL-10). Meanwhile, it lowered malondialdehyde (MDA), nitric oxide (NO) and nuclear factor erythroid 2-related factor 2 (NRF-2) levels with restoration of glutathione (GSH), and glutathione peroxidase (GPx). Regarding mitogen-activated protein kinase (MAPK) pathway, tangeretin attenuated cisplatin-induced increase in phospho-p38, phospho-c-Jun N-terminal kinase (p-JNK) and phospho-extracellular signal-regulated kinase (p-ERK1/2) in liver tissues. In addition, tangeretin downregulated Bax expression with augmentation of Bcl-2 promoting liver cell survival. Our results highlight the protective effects of tangeretin against cisplatin-induced acute hepatic injury via the concerted modulation of inflammation, oxidative stress, MAPKs and apoptotic pathways.

One of the standards for cancer treatment is cancer immunotherapy which treats both primary and metastasized tumors. Although cancer immunotherapeutics show better outcomes as compared with conventional approaches of cancer treatment, the currently used cancer immunotherapeutics have limited application in delivering cancer antigens to immune cells. Conversely, in solid tumors, tumor microenvironment suppresses the immune system leading to the evasion of anticancer immunity. Some promising attempts have been made to overcome these drawbacks by using different approaches, for instance, the use of biomaterial-based nanoparticles. Accordingly, various studies involving the application of nanoparticles in cancer immunotherapy have been discussed in this review article. This review not only describes the modes of cancer immunotherapy to reveal the importance of nanoparticles in this modality but also narrates nanoparticle-mediated delivery of cancer antigens and therapeutic supplements. Moreover, the impact of nanoparticles on the immunosuppressive behavior of tumor environment has been discussed. The last part of this review deals with cancer immunotherapy using a combination of traditional interventional oncology approach and image-guided local immunotherapy against cancer. According to recent studies, cancer therapy can potentially be improved through nanoparticle-based immunotherapy. In addition, drawbacks associated with the currently used cancer immunotherapeutics can be fixed by using nanoparticles.

Leptin resistance and co-existing insulin resistance is considered as hallmark of diet-induced obesity. Here, we investigated therapeutic potential of hesperidin to improve leptin and insulin resistance using high fat diet (HFD)-induced obese experimental animal model. We also performed in silico studies to validate therapeutic effectiveness of hesperidin by performing protein-ligand docking and molecular dynamics simulation studies. Group 1 was identified as control group receiving vehicle only. Group 2 was marked as non-treated group receiving 60% HFD. While, other groups were treated daily with orlistat (120 mg/kg/d), hesperidin (55 mg/kg/d), combination of hesperidin (55 mg/kg/d) + orlistat (120 mg/kg/d). Hesperidin alone (P<0.001) and particularly in combination with orlistat (P<0.001), resulted in controlling the levels of HFD-altered biomarkers including random and fasting state of glycemia, leptin and insulin resistance. Similarly, hesperidin also improved the serum and tissue levels of leptin, interleukin-6 and tumor necrosis factor-alpha more significantly (P<0.05) when compared with that of orlistat. These results were found to be in accordance with the results of histopathological examination of pancreas, liver and adipose tissues. In-silico studies also proved that hesperidin binds to leptin receptor with higher affinity as compared to that of orlistat and induces the favorable variations in geometrical conformation of leptin receptor to promote its association with leptin which may lead to the cascades of reactions culminating the lipolysis of fats that may ultimately lead to cure obesity. The results of this study may be a significant expectation among the forthcoming treatment strategies for leptin and insulin resistance.

Background/Aims: Camel milk (CM) has shown beneficial anti-inflammatory actions in several experimental and clinical settings. So far, its effect on rheumatoid arthritis (RA) has not been previously explored. Thus, the current work aimed to evaluate the effects of CM in Adjuvant-induced arthritis and air pouch edema models in rats, which mimic human RA. Methods: CM was administered at 10 ml/kg orally for 3 weeks starting on the day of Freund’s adjuvant paw inoculation. The levels of TNF-α and IL-10 were measured by ELISA while the protein expression of NF-κBp65, COX-2 and iNOS was detected by immunohistochemistry. The expression of MAPK target proteins was assessed by Western blotting. Results: CM attenuated paw edema, arthritic index and gait score along with dorsal pouch inflammatory cell migration. CM lowered the TNF-α and augmented the anti-inflammatory IL-10 levels in sera and exudates of arthritic rats. It also attenuated the expression of activated NF-κBp65, COX-2 and iNOS in the lining of the dorsal pouch. Notably, CM inhibited the MAPK pathway signal transduction via lowering the phosphorylation of p38 MAPK, ERK1/2 and JNK1/2 in rat hind paws. Additionally, CM administration lowered the lipid peroxide and nitric oxide levels and boosted glutathione and total anti-oxidant capacity in sera and exudates of animals. Conclusion: The observed CM downregulation of the arthritic process may support the interest of CM consumption as an adjunct approach for the management of RA.

Calcitonin was discovered as a peptide hormone that was known to reduce the calcium levels in the systemic circulation. This hypocalcemic effect is produced due to multiple reasons such as inhibition of bone resorption or suppression of calcium release from the bone. Thus, calcitonin was said as a primary regulator of the bone resorption process. This is the reason why calcitonin has been used widely in clinics for the treatment of bone disorders such as osteoporosis, hypercalcemia, and Paget’s disease. However, presently calcitonin usage is declined due to the development of efficacious formulations of new drugs. Calcitonin gene-related peptides and several other peptides such as intermedin, amylin, and adrenomedullin (ADM) are categorized in calcitonin family. These peptides are known for the structural similarity with calcitonin. Aside from having a similar structure, these peptides have few overlapping biological activities and signal transduction action through related receptors. However, several other activities are also present that are peptide specific. In vitro and in vivo studies documented the posttreatment effects of calcitonin peptides, i.e., positive effect on bone osteoblasts and their formation and negative effect on osteoclasts and their resorption. The recent research studies carried out on genetically modified mice showed the inhibition of osteoclast activity by amylin, while astonishingly calcitonin plays its role by suppressing osteoblast and bone turnover. This article describes the review of the bone, the activity of the calcitonin family of peptides, and the link between them.

Background: Inflammation is a strong reaction of the non-specific natural immune system that helps to start protective responses against encroaching pathogens and develop typical immunity against intruding factors. However, prolonged inflammation may lead to chronic autoimmune diseases. For thousands of years, medicinal plants have served as an excellent source of treatment for chronic pathologies such as metabolic diseases. Purpose: The present study aims to evaluate the anti-inflammatory and anti-angiogenic potential of Moringa olifera Lam. extract ( MO ) and Moringa -loaded nanoclay films. Methods: The extract preparation was done through the maceration technique using absolute methanol (99.7%) and labelled as Mo. Me . Mo. Me- loaded nanoclay-based films were prepared by using pectin and sericin ( Table 1 ). The in vitro studies characterized the film thickness, moisture, and phytochemical contents. The in vivo anti-inflammatory tests involved using a cotton pellet-induced granuloma model assay. In addition, the chick chorioallantoic membrane (CAM) assay was employed for angiogenesis activity. Results: The phytochemical analysis of the extract confirmed the presence of alkaloids, glycosides, flavonoids and phytosterol. This extract contained quercetin in a large quantity. Cotton-pellet induced granuloma model study revealed a comparable ( p > 0.05) effect of a high dose of Mo. Me (500 mg/kg) as compared with standard drug. Noteworthy, data obtained through the RT-PCR technique manifested the dose-dependent anti-oedematous effect of Moringa olifera via downregulation of TNF-α and interleukin-1ß. The findings of the CAM assay exhibited a remarkable anti-angiogenic activity of Mo. Me loaded nanoclay films, showing diffused vasculature network in the macroscopic snapshot. Conclusion: Moringa olifera and its nanocomposite films have therapeutic potential against inflammation.

Cadmium, a ubiquitous environmental toxicant, disrupts testicular function and fertility. The dipeptidyl peptidase-4 inhibitor linagliptin has shown pronounced anti-inflammatory and anti-apoptotic features; however, its effects against cadmium-evoked testicular impairment have not been examined. Herein, the present study investigated targeting inflammation, apoptosis, and autophagy by linagliptin for potential modulation of cadmium-induced testicular dysfunction in rats. After 60 days of cadmium chloride administration (5 mg/kg/day, by gavage), testes, epididymis, and blood were collected for analysis. The present findings revealed that linagliptin improved the histopathological lesions, including spermatogenesis impairment and germ cell loss. Moreover, it improved sperm count/motility and serum testosterone. The favorable effects of linagliptin were mediated by curbing testicular inflammation seen by dampening of HMGB1/TLR4 pathway and associated lowering of nuclear NF-κBp65. In tandem, linagliptin suppressed the activation of NLRP3 inflammasome/caspase 1 axis with consequent lowering of the pro-inflammatory IL-1β and IL-18. Jointly, linagliptin attenuated testicular apoptotic responses seen by Bax downregulation, Bcl-2 upregulation, and suppressed caspase 3 activity. With respect to autophagy, linagliptin enhanced the testicular autophagy flux seen by lowered accumulation of p62 SQSTM1 alongside upregulation of Beclin 1. The observed autophagy stimulation was associated with elevated AMPK (Ser487) phosphorylation and lowered mTOR (Ser2448) phosphorylation, indicating AMPK/mTOR pathway activation. In conclusion, inhibition of testicular HMGB1/TLR4/NLRP3 pro-inflammatory axis and apoptosis alongside stimulation of autophagy were implicated in the favorable actions of linagliptin against cadmium-triggered testicular impairment.

Chemotherapeutics can induce oxidative stress, inflammation, apoptosis, mitochondrial dysfunction, and abnormalities in neurotransmitter metabolism leading to toxicity. Because there have been no therapeutic strategies developed to target inflammation and oxidative stress, there is a continuing need for new and improved therapy. As a result, there has been increasing interest in complementary and alternative medicine with anticancer potential. Studies have shown that the antioxidant activities and anti-inflammatory effects of citrus fruits are promising natural phytochemicals in the development of new anticancer agents. Tangeretin is a naturally polymethoxylated flavone compound extracted from the citrus peel that has shown significant intestinal absorption and adequate bioavailability, with the added benefit of promoting longevity. In addition, tangeretin is known to exhibit considerable selective toxicity to many types of cancer cell proliferation such as ovarian, brain, blood, and skin cancer. Evidence indicates that tangeretin acts through several mechanisms including growth inhibition, induction of apoptosis, autophagy, antiangiogenesis, and estrogenic-like effects. Furthermore, tangeretin works through mitigating levels of inflammatory mediators in the immune system. Using tangeretin in combination with clinically applied anticancer drugs could be a good strategy for increasing the efficiency of these agents and protecting noncancerous cells from damage caused by chemotherapy. The purpose of this review is to highlight the protective effects of a novel natural product, tangeretin against chemotherapeutic-induced toxicity. The development of chemoprevention strategies can lead to significant health care improvement in cancer survivors. Thus, study outcomes may attract more investigators to conduct tangeretin-related research and find out potentially significant impacts on health care of cancer patients and decreased health problems associated with chemotherapeutics-induced toxicity.

Renal damage is a devastating adverse effect for cyclosporine; a widely used immunosuppressant drug. The present work examined the potential of camel milk, a natural agent with marked anti-inflammatory/antioxidant properties, to attenuate cyclosporine-induced renal injury. The kidney tissue was examined with the aid of Western blotting, immunohistochemistry, biochemical assays, including colorimetric and ELISA kits. The present findings revealed that camel milk (10 mL/kg/day; for 3 weeks by gavage) significantly lowered serum creatinine, BUN, and KIM-1 renal dysfunction markers. Mechanistically, camel milk inhibited renal inflammation, as seen by significant decrease of the pro-inflammatory cytokines (MCP-1, TNF-α, IL-1β, and IL-18) and extracellular degradation signals (MMP-2 and MMP-9) and enhanced the generation of the anti-inflammatory IL-10. Moreover, it inhibited the upstream pro-inflammatory p38/ERK/JNK MAPK pathway by lowering the phosphorylation of the 3 subfamilies of MAPKs (p38 MAPK, JNK1/2, and ERK1/2). Furthermore, camel milk curbed the NF-κB pathway activation by downregulating the protein expression of activated NF-κBp65, p-NF-κBp65, and p-IκBα proteins. Additionally, camel milk inhibited renal oxidative stress by lowering the MPO activity and augmenting the reduced/oxidized glutathione ratio and total antioxidant capacity. These findings propose that camel milk may be a promising agent that inhibits cyclosporine-triggered renal inflammation via curtailing the p38/ERK/JNK MAPK and NF-κB pathways, matrix metalloproteinases, and pro-inflammatory cytokines.