Dietary chamomile flowers extract improved performance and mitigated aflatoxin B1 toxicity in rabbits.

Aflatoxin B1 (AFB1) is among the poisonous mycotoxins that contaminate food and feed. Limited studies are available on the efficacy of chamomile (Cha) against oxidative stress, liver damage and pro-inflammatory response induced by AFB1. The present study aims to evaluate the effects of Cha on the performance and protective effects against AFB1 in growing rabbits. The experimental rabbits were divided into four different groups, including Cha (70 mg kg day-1), AFB1 (AF; 30 µg kg day-1), AFB1+Cha (AFLCha) and control (CON). The results indicated that the AFB1 treatment had lower values of performance, and carcass parameters compared to the Cha and AFLCha treatments. Furthermore, the Cha and AFLCha groups had lower values of liver and kidney function activities compared to the AFB1 treatment. The higher values of antioxidant enzymes were observed in Cha and AFLCha treatments than in the AFB1 treatment. AFB1 treatments had higher levels of malondialdehyde and liver functions with lower levels of antioxidant enzymes (glutathione and superoxide dismutase) compared to Cha and CON groups. In conclusion, dietary Cha could mitigate the oxidative stress of AFB1-induced liver deterioration.

New Thiazolyl-Pyrazoline Derivatives as Potential Dual EGFR/HER2 Inhibitors: Design, Synthesis, Anticancer Activity Evaluation and In Silico Study.

A new series of thiazolyl-pyrazoline derivatives (4a-d, 5a-d 6a, b, 7a-d, 8a, b, and 10a, b) have been designed and synthesized through the combination of thiazole and pyrazoline moieties, starting from the key building blocks pyrazoline carbothioamides (1a-b). These eighteen derivatives have been designed as anticipated EGFR/HER2 dual inhibitors. The efficacy of the developed compounds in inhibiting cell proliferation was assessed using the breast cancer MCF-7 cell line. Among the new synthesized thiazolyl-pyrazolines, compounds 6a, 6b, 10a, and 10b displayed potent anticancer activity toward MCF-7 with IC50 = 4.08, 5.64, 3.37, and 3.54 µM, respectively, when compared with lapatinib (IC50 = 5.88 µM). In addition, enzymatic assays were also run for the most cytotoxic compounds (6a and 6b) toward EGFR and HER2 to demonstrate their dual inhibitory activity. They revealed promising inhibition potency against EGFR with IC50 = 0.024, and 0.005 µM, respectively, whereas their IC50 = 0.047 and 0.022 µM toward HER2, respectively, compared with lapatinib (IC50 = 0.007 and 0.018 µM). Both compounds 6a and 10a induced apoptosis by arresting the cell cycle of the MCF-7 cell line at the G1 and G1/S phases, respectively. Molecular modeling studies for the promising candidates 6a and 10a showed that they formed the essential binding with the crucial amino acids for EGFR and HER2 inhibition, supporting the in vitro assay results. Furthermore, ADMET study predictions were carried out for the compounds in the study.

Screening for PIK3CA mutations among Saudi women with ovarian cancer.

The study aimed to screen for PIK3CA gene mutations among Saudi women with Ovarian Cancer. The study included 298 Saudi women with epithelial ovarian cancers (EOC). DNA sequence analysis was employed to screen for the mutations. DNA sequence analysis of a coding region of exon 9 and 20 of PIK3CA gene revealed mutations in 37/298 (12.4%) EOC patients. About 21/37(56.8%) somatic mutations were identified in exons 9, and 16/37(43.2%) in exon 20. All analysed mutations were missense mutations, the frequencies of which varied from 2.7% to 43.2%. PIK3CA mutation was found to be significantly associated with age (p = .023), grade (p = .001) and histological types (p = .032). Only 6.6% of serous carcinomas and 3.8% of endometrioid had PIK3CA mutation. The Mutated PIK3CA gene was significantly involved in the pathogenesis of EOC among Saudi women. PIK3CA gene mutation and overexpression represent important clinical implications for diagnosis, and prognosis, which can be utilised for better EOC management.Impact statementWhat is already known on this subject? The detailed molecular and genetic phenomenon underlying the progression of these tumours is still unclear. Recently, the pathogenesis of ovarian cancer has been attributed to mutations of PIK3CA.What do the results of this study add? Mutation in the PIK3CA gene leads to altered PI3K/AKT signalling pathways responsible for the progression of the epithelial ovarian cancer.What are the implications of these findings for clinical practice and/or further research? The Mutated PIK3CA gene was significantly involved in the pathogenesis of EOC among Saudi women. PIK3CA gene mutation and overexpression represent important clinical implications for diagnosis, and prognosis, which can be utilised for better EOC management.

Tryptophan-tagged peptide from serine threonine-protein kinase of Channa striatus improves antioxidant defence in L6 myotubes and attenuates caspase 3-dependent apoptotic response in zebrafish larvae.

This study reports the antioxidant property and molecular mechanism of a tryptophan-tagged peptide derived from a teleost fish Channa striatus of serine threonine-protein kinase (STPK). The peptide was tagged with tryptophan to enhance the antioxidant property of STPK and named as IW13. The antioxidant activity of IW13 peptide was investigated using in vitro methods such as DPPH, ABTS, superoxide anion radical scavenging and hydrogen peroxide scavenging assay. Furthermore, to investigate the toxicity and dose response of IW13 peptide on antioxidant defence in vitro, L6 myotubes were induced with generic oxidative stress due to exposure of hydrogen peroxide (H2O2). IW13 peptide exposure was found to be non-cytotoxic to L6 cells in the tested concentration (10, 20, 30, 40 and 50 µM). Also, the pre-treatment of IW13 peptide decreased the lipid peroxidation level and increased glutathione enzyme activity. IW13 peptide treatment upregulated the antioxidant enzyme genes: GPx (glutathione peroxidase), GST (glutathione S transferase) and GCS (glutamine cysteine synthase), in vitro in L6 myotubes and in vivo in zebrafish larvae against the H2O2-induced oxidative stress. The results demonstrated that IW13 renders protection against the H2O2-induced oxidative stress through a cellular antioxidant defence mechanism by upregulating the gene expression, thus enhancing the antioxidant activity in the cellular or organismal level. The findings exhibited that the tryptophan-tagged IW13 peptide from STPK of C. striatus could be a promising candidate for the treatment of oxidative stress-associated diseases.

Cystic echinococcosis: Development of an intermediate host rabbit model for using in vaccination studies.

The aims of this study were an establishment of the domestic rabbit as an intermediate host for cystic echinococcosis (CE) and to evaluate the potency of the crude germinal layer and the protoscoleces antigens to protect against the CE. Firstly; Two groups of white Newzeland rabbits were infected orally either by 5000 active oncospheres or viable protoscoleces separately. After 20 weeks, the slaughtered rabbits showed the presence of hydatid cysts at different internal organs. Molecular detection of the resulted cysts was conducted. Secondly; 27 rabbits were divided into nine groups (n = 3). Groups 1 and 2 were immunized with the crude germinal layer antigen while the groups 3 and 4 were immunized with the crude protoscoleces antigen. Groups 5 and 6 received the adjuvant mineral oil. Groups 7 and 8 were used as positive control. The last 9 group was kept as a negative control. The obtained results showed a significant high protection percentage of 83.4% and high antibody titer was recorded in groups that received the crude germinal layer antigen comparing with the groups that immunized with the crude protoscoleces antigen as their protection percentage was 66.7% with lower IgG response. In conclusion, the domestic rabbits could be used as a laboratory model for CE. Developing of the germinal layer antigen is more immunogenic than the protoscoleces one and could be used as a promising vaccine. Attention should be directed towards the existing rabbit in the environment adjacent to infected dogs as it could be a part of Echinococcus life cycle.

Phorbol 12-Myristate 13-Acetate Induced Toxicity Study and the Role of Tangeretin in Abrogating HIF-1α-NF-κB Crosstalk In Vitro and In Vivo.

Phorbol 12-myristate 13-acetate (PMA) is a potent tumor promoter and highly inflammatory in nature. Here, we investigated the toxic effects of PMA on different model system. PMA (10 µg) caused chromosomal aberrations on the Allium cepa root tip and induced mitotic dysfunction. Similarly, PMA caused embryonic and larval deformities and a plummeted survivability rate on zebrafish embryo in a dose-dependent manner. Persistently, PMA treatment on immortalized human keratinocyte human keratinocyte (HaCaT) cells caused massive inflammatory rush at 4 h and a drop in cell survivability at 24 h. Concomitantly, we replicated a cutaneous inflammation similar to human psoriasis induced by PMA. Herein, we used tangeretin (TAN), as an antagonist to counteract the inflammatory response. Results from an in vivo experiment indicated that TAN (10 and 30 mg/kg) significantly inhibited PMA stimulated epidermal hyperplasia and intra-epidermal neutrophilic abscesses. In addition, its treatment effectively neutralized PMA induced elevated reactive oxygen species (ROS) generation on in vitro and in vivo systems, promoting antioxidant response. The association of hypoxia-inducible factor 1-alpha (HIF-1α)-nuclear factor kappa-light-chain-enhancer of activated b cells (NF-κB) crosstalk triggered by PMA enhanced PKCα-ERK1/2-NF-κB pathway; its activation was also significantly counteracted after TAN treatment. Conclusively, we demonstrated TAN inhibited the nuclear translocation of HIF-1α and NF-κB p65. Collectively, TAN treatment ameliorated PMA incited malignant inflammatory response by remodeling the cutaneous microenvironment.

Synergistic Anti-Breast-Cancer Effects of Combined Treatment With Oleuropein and Doxorubicin In Vivo.

CONTEXT: Breast cancer is a leading cause of cancer fatalities among women worldwide. Of the more than 80% of patients who receive adjuvant chemotherapy, approximately 40% relapse. The majority of these patients die of disseminated metastatic disease, which emphasizes the need for new therapeutic strategies. OBJECTIVE: The study intended to investigate the anticancer effects of oleuropein (OL) and doxorubicin (DOX) individually and in combination on breast tumor xenografts and also to evaluate the molecular pathways involved. DESIGN: The research team designed in vivo (animal) and in vitro (cell culture) studies. SETTING: The study was performed in the College of Science of King Saud University in the University Center for Women Students (Riyadh, Saudi Arabia). ANIMALS: The study involved 40 female, nude mice (BALB/c OlaHsd-foxn1). INTERVENTION: The mice were injected subcutaneously with MDA-MB-231 human breast cancer cells. After the growth of tumors, the animals were randomly divided into 4 groups to receive intraperitoneal injections: (1) group 1 (control group)-dimethyl sulfoxide, (2) group 2 (intervention group)-50 mg/kg of OL, (3) group 3 (intervention group)-2.5 mg/kg of DOX, and (4) group 4 (intervention group)-1.5 mg/kg of DOX, immediately followed by 50 mg/kg of OL. The OL was extracted from Manzanillo olive trees (Olea europaea) grown in Tabouk, Saudi Arabia. OUTCOME MEASURES: The measures included the isolation and primary culture of the tumor xenografts, apoptosis analysis by annexin V, cellular lysate preparation, and immunoblotting. RESULTS: The volume of the tumor increased aggressively, reaching 173 mm3 in the control animals in a time-dependent manner. On the other hand, a sharp drop, to 48.7 mm3, in the volume of the tumor was observed with the 2 drugs combined, a more than 3-fold decrease. The effect was mediated through the induction of apoptosis via the mitochondrial pathway. The combined treatment downregulated the antiapoptosis and proproliferation protein, nuclear factor-kappa Β, and its main oncogenic target cyclin D1. Furthermore, it inhibited the expression of BCL-2 and survivin. This inhibition could explain the cooperative suppression of the proliferation of breast tumor xenografts and the induction of apoptosis by the combined effect of the compounds used. CONCLUSIONS: The key findings clearly indicate the synergistic efficacy of DOX with natural and nontoxic OL against breast tumor xenografts.

Probiotics and yogurt modulate oxidative stress and fibrosis in livers of Schistosoma mansoni-infected mice.

BACKGROUND: Considerable morbidity, mortality, and economic loss result from schistosomiasis infection. Deposition of Schistosoma eggs in the hepatic portal vein is considered as the main causative agent for the development of liver fibrosis and subsequent liver cirrhosis. Probiotics are exogenous and beneficial microorganisms to living hosts against the harmful effect of many parasites. Strong evidence suggests the importance of probiotics in the control strategy of helminth. The ultimate goal of this study is to evaluate the protective effect of probiotics and yogurt on Schistosoma mansoni-induced oxidative stress and hepatic fibrosis in mice. METHODS: Mice were infected by tail immersion of schistosomal cercariae followed by an oral treatment with either probiotics or yogurt for one week before infection and immediately post-infection. Mice were scarified on day 56 following infection with S. mansoni and liver sample were obtained. RESULTS: We showed that oral administration of probiotics or yogurt revealed a significant reduction in worm number, egg load, and granuloma size in liver tissue, which is mainly assigned to the decreased expression level of matrix metalloproteinases 9 (MMP-9) in liver tissue. A significant reduction in the oxidative stress markers-induced by S. mansoni infection including lipid peroxidation and nitrite/nitrate was also detected. The level of some antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) and reduced glutathione was greatly enhanced. Furthermore, treatment with probiotics or yogurt inhibited apoptosis in hepatic tissue, which is mainly assigned to the decreased expression level of caspases-3 in liver tissue. CONCLUSION: Our findings represent the promising anti-schistosomal activities of probiotics and yogurt.

Antischistosomal and anti-inflammatory activity of garlic and allicin compared with that of praziquantel in vivo.

BACKGROUND: Schistosomiasis is an acute and chronic zoonotic parasitic disease caused by trematode worms. The host inflammatory response to schistosome eggs leads to perioval granulomata formation, mainly in the liver and intestine. This study investigated the potential antischistosomal and anti-inflammatory activity of both garlic extract and allicin on liver fibrotic markers in BALB/c mice with schistosomiasis (S. mansoni infection) compared with that of the commonly used drug, praziquantel (PZQ). METHODS: In this study, 140 female BALB/c mice (7-weeks old) were divided into seven groups with 20 mice each. Six groups were infected with S. mansoni cercariae and treated with garlic, allicin, or PZQ. The seventh group was the negative control. Twenty-four hours after the final treatment, the mice were euthanised and perfused for worm recovery. The liver and intestines were harvested for parasitological and histological assessment and to analyse the proinflammatory cytokine mRNA expression. RESULTS: Prophylactic administration of garlic and allicin to the infected mice significantly reduced the worm burden. Serum concentrations of liver fibrosis markers and proinflammatory cytokines were also reduced. PZQ was the most efficacious for reduction in the number of worms. These results are similar to those normally obtained using PZQ. CONCLUSIONS: Crushed garlic homogenate and allicin are potential complementary treatments that may be used with PZQ.

Protective Effect of Fragaria ananassa Crude Extract on Cadmium-Induced Lipid Peroxidation, Antioxidant Enzymes Suppression, and Apoptosis in Rat Testes.

Cadmium is a deleterious environmental pollutant that threats both animals and human health. Oxidative stress and elevated levels of reactive oxygen species (ROS) have recently been reported to be the main cause of cellular damage as a result of cadmium exposure. We investigate, here, the protective effect of strawberry crude extracts on cadmium-induced oxidative damage of testes in rats. Four groups (n = 8) of 32 adult male Wistar rats weighing 160-180 g were used. The control group received 0.9% saline solution all over the experimental period (5 days). Group 2 was intraperitoneally injected with 6.5 mg/kg CdCl2. Group 3 was provided only with an oral administration of strawberry methanolic extract (SME) at a dose of 250 mg/kg. Group 4 was treated with SME before cadmium injection with the same mentioned doses. It was shown that cadmium exposure results in a significant decrease in both relative testicular weight and serum testosterone level. Analyzing the oxidative damaging effect of cadmium on the testicular tissue revealed the induction of oxidative stress markers represented in the elevated level of lipid peroxidation (LPO), nitric oxide (NO), and a decrease in the reduced glutathione (GSH) content. Considering cadmium toxicity, the level of the antioxidant enzyme activities including catalase (CAT), superoxide dismutase (SOD2), glutathione peroxidase (GPx1), and glutathione reductase (GR) were markedly decreased. Moreover, gene expression analysis indicated significant upregulation of the pro-apoptotic proteins, bcl-2-associated-X-protein (BAX), and tumor necrosis factor-α (TNFA) in response to cadmium intoxication, while significant downregulation of the anti-apoptotic, B-cell lymphoma 2 (BCL2) gene was detected. Immunohistochemistry of the testicular tissue possessed positive immunostaining for the increased level of TNF-α, but decreased number of proliferating cell nuclear antigen (PCNA) stained cells. Administration of SME debilitated the deleterious effect of cadmium via reduction of both LPO and NO levels followed by a significant enhancement in the gene expression level of CAT, SOD2, GPX1, GR, nuclear factor-erythroid 2-related factor 2 (NFE2L2), heme oxygenase-1 (HMOX1), Bcl-2, and PCNA. In addition, the SME treated group revealed a significant increase in the level of testosterone and GSH accompanied by a marked decrease in the gene expression level of Bax and TNF-α. In terms of the summarized results, the SME of Fragaria ananassa has a protective effect against cadmium-induced oxidative damage of testes.

Ceratonia siliqua pod extract ameliorates Schistosoma mansoni-induced liver fibrosis and oxidative stress.

BACKGROUND: Schistosomiasis is a prevalent parasitic disease found predominantly in tropical and sub-tropical areas of the developing world, with the second highest socioeconomic and public health burden despite strenuous control efforts. In the present study, we aimed to investigate the ameliorative effects of Ceratonia siliqua pod extract (CPE) on liver fibrosis and oxidative stress in mice infected with Schistosoma mansoni. METHODS: The schistosomal hepatopathologic mouse model was established by tail immersion with schistosomal cercaria. The extract was given daily for 10 days beginning 42 days post-infection. Liver samples were obtained from mice sacrificed 9 weeks after infection. Liver histopathological changes were observed with hematoxylin-eosin and Masson trichrome staining. RESULTS: Typical schistosomal hepatopathologic changes were induced in the untreated mice. However, the oral administration of CPE was effective in reducing worm number and the egg load in the liver. This treatment also decreased granuloma size and collagen deposition by inhibiting tissue inhibitor of metalloproteinases-2 (TIMP-2) expression. Schistosomal infection induced oxidative stress by increasing lipid peroxidation (LPO) and nitrite/nitrate (nitric oxide; NO) production along with concomitant decreases in glutathione (GSH) and various antioxidant enzymes, including superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. However, treatment of mice with CPE at 300 or 600 mg/kg inhibited LPO and NO production, increased GSH content, and restored the activities of the antioxidant enzymes compared with untreated infected mice. Furthermore, treatment with CPE inhibited apoptosis, as indicated by the reduced Bax expression in hepatic tissue. CONCLUSION: These data indicated that extracts from Ceratonia siliqua pods may play an important role in combating schistosomal hepatopathology and may inhibit granuloma formation and liver fibrosis through down-regulation of TIMP-2 expression.

The protective properties of melatonin against aluminium-induced neuronal injury.

Aluminium (Al) toxicity is closely linked to the pathogenesis of Alzheimer's disease (AD). This experimental study investigated the neuroprotective effect of melatonin (Mel; 10 mg/kg bwt) on aluminium chloride (AlCl3 ; 34 mg/kg bwt) induced neurotoxicity and oxidative stress in rats. Adult male albino Wistar rats were injected with AlCl3 for 7 days. The effect on brain structure, lipid peroxidation (LPO), nitric oxide (NO) levels, glutathione (GSH) content, antioxidant enzymes (SOD, CAT, GPx and GR), apoptotic proteins (Bax and Bcl-2) and an apoptotic enzyme (caspase-3) was investigated. No apparent changes occurred following the injection of melatonin. Melatonin pretreatment of the AlCl3 -administered rats reduced brain damage, and the tissues appeared like those of the control rats. Compared to treatment with AlCl3 , pretreatment with melatonin decreased LPO and NO levels and increased the GSH content and antioxidant enzyme activity. Moreover, melatonin increased the levels of the anti-apoptotic protein, Bcl-2, decreased the levels of the pro-apoptotic protein, Bax, and inhibited caspase-3 activity. Therefore, our results indicate that melatonin may provide therapeutic value against aluminium-induced oxidative stress and histopathological alternations in the rat brain and that these effects may be related to anti-apoptotic and antioxidant activities.

Protective effects of pomegranate (Punica granatum) juice on testes against carbon tetrachloride intoxication in rats.

BACKGROUND: Pomegranate fruit has been extensively used as a natural medicine in many cultures. The present study was aimed at evaluating the protective effects of pomegranate (Punica granatum) juice against carbon tetrachloride (CCl4)-induced oxidative stress and testes injury in adult Wistar rats. METHODS: Twenty eight Wistar albino male rats were divided equally into 4 groups for the assessment of protective potential of pomegranate juice. Rats of group I (control) received only vehicles and had free access to food and water. Rats of groups II and IV were treated with CCl4 (2 ml/kg bwt) via the intraperitoneal route once a week for ten weeks. The pomegranate juice was supplemented via drinking water 2 weeks before and concurrent with CCl4 treatment to group IV. Group III was supplemented with pomegranate juice for twelve weeks. The protective effects of pomegranate on serum sex hormones, oxidative markers, activities of antioxidant enzymes and histopathology of testes were determined in CCl4-induced reproductive toxicity in rats. RESULTS: Pomegranate juice showed significant elevation in testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) those depleted by the injection of CCl4. Activity levels of endogenous testesticular antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) and glutathione (GSH) contents were increased while lipid peroxidation (LPO) and nitric oxide (NO) were decreased with pomegranate juice. Moreover, degeneration of germ and Leydig cells along with deformities in spermatogenesis induced after CCl4 injections were restored with the treatment of pomegranate juice. CONCLUSION: The results clearly demonstrated that pomegranate juice augments the antioxidant defense mechanism against carbon tetrachloride-induced reproductive toxicity and provides evidence that it may have a therapeutic role in free radical mediated diseases.

Assessment of oxidative stress and tissue damage in Echinococcus granulosus naturally infected bovine liver.

Echinococcus granulosus is a zoonotic parasite infects many livestock species, especially cattle, sheep, goat and buffalo, causing cystic echinococcosis. The aim of this study was to demonstrate the presence of the parasite and parasitic tissue damage histopathologically and to determine the role of oxidative stress in the tissue damage through the immunohistochemical detection of the oxidative damage-marker malondialdehyde (MDA) and the antioxidant response-marker superoxide dismutase (SOD). The material of the study consisted of 20 liver samples with Echinococcus cysts and 10 E.granulosus- negative healthy liver samples obtained from different cattle at various times from slaughterhouses in Kirikkale province, Turkey. Histopathologically, Echinococcus cysts of various sizes were observed along with the surrounding fibrous connective tissue. Giant cells, mononuclear cells, and eosinophilic leukocytes were found between the fibrous connective tissue and the cyst. In the parenchymal tissue distant from the cyst, inflammatory changes were observed, including vacuolation and necrosis in hepatocytes, congestion and dilation sinusoidal capillaries. Immunohistochemically, MDA immunopositivity was observed in both hepatocytes surrounding the cyst and areas distant from the cyst, while SOD immunopositivity was mainly detected in fibrous connective tissue and hepatocytes surrounding the Echinococcus cysts. A significant increase in MDA immunoreactivity was observed in E.granulosus s.l.-infected livers. Although no statistically significant change was observed in SOD immunopositivity in the liver tissues with cystic echinococcosis, regional variations were noted. Germinal layer (GL) of Echinococcus cyst showed immunopositive staining for MDA, while laminated layer (LL) exhibited immunonegative staining. To the authors' best understanding, this study represents a pioneering effort in showcasing and evaluating the immunoreactivities of MDA and SOD within the liver tissue afflicted with Echinococcus cysts. Simultaneously, the examination extends to encompass tissue damage and the infiltration of inflammatory cells. This study highlights the role of oxidative stress in the pathogenesis of Cystic Echinococcosis (CE) and the need for further investigation of antioxidant defense mechanisms and their regional variations.

Serum 25-Hydroxyvitamin D Is Inversely Associated with Nasopharyngeal Carcinoma: A Hospital-Based Matched Case-Control Study in Malaysia.

Serum 25(OH)D deficiency consistently demonstrated molecular mechanisms through which chronic inflammation is associated with the risk of nasopharyngeal carcinoma (NPC). This study aimed to determine the association between serum 25(OH)D and NPC. A matched case-control study was conducted at two local hospitals. A total of 300 histologically confirmed NPC cases were matched with controls for age, gender, and ethnicity, and assessed for vitamin D status and other nutritional factors. Mean Vitamin D concentration was significantly lower among cases compared to controls (63.17 ± 19.15 nmol/L and 67.34 ± 23.06 nmol/L) (t = -2.41, p = 0.016). Multiple conditional logistic regression analysis indicated that higher levels of serum 25(OH)D were associated with reduced odds of NPC (AOR = 0.73, 95% CI = 0.57-0.94, p = 0.016) controlling for confounders including BMI, physical activity, smoking status, alcohol consumption, consumption of food high in vitamin D, salted fish consumption, and family history of NPC. There was a significant association between inadequate serum 25(OH)D status with accumulation of four risk factors and increased odds of getting NPC using polynomial regression analysis. Increased NPC odds ratios were observed after sequential accumulation of additional risk factors with the presence of inadequate serum 25(OH)D status (OR = 0.54, 95% CI = 0.27, 4.77, p = 0.322, OR = 1.04, 95% CI = 0.64, 1.72, p = 0.267, OR = 1.15, 95% CI = 0.73, 1.80, p = 0.067, OR = 1.93, 95% CI = 1.13, 3.31, p = 0.022, and OR = 5.55, 95% CI = 1.67, 10.3, p < 0.001 respectively). Future research in Malaysia should involve both prospective cohort studies and randomized controlled trials to confirm and further clarify the role of vitamin D in NPC outcomes.

An insight review on the neuropharmacological effects, mechanisms of action, pharmacokinetics and toxicity of mitragynine.

Mitragynine is one of the main psychoactive alkaloids in Mitragyna speciosa Korth. (kratom). It has opium-like effects by acting on µ-, δ-, and κ-opioid receptors in the brain. The compound also interacts with other receptors, such as adrenergic and serotonergic receptors and neuronal Ca2+ channels in the central nervous system to have its neuropharmacological effects. Mitragynine has the potential to treat diseases related to neurodegeneration such as Alzheimer's disease and Parkinson's disease, as its modulation on the opioid receptors has been reported extensively. This review aimed to provide an up-to-date and critical overview on the neuropharmacological effects, mechanisms of action, pharmacokinetics and safety of mitragynine as a prospective psychotropic agent. Its multiple neuropharmacological effects on the brain include antinociceptive, anti-inflammatory, antidepressant, sedative, stimulant, cognitive, and anxiolytic activities. The potential of mitragynine to manage opioid withdrawal symptoms related to opioid dependence, its pharmacokinetics and toxic effects were also discussed. The interaction of mitragynine with various receptors in the brain produce diverse neuropharmacological effects, which have beneficial properties in neurological disorders. However, further studies need to be carried out on mitragynine to uncover its complex mechanisms of action, pharmacokinetics, pharmacodynamic profiles, addictive potential, and safe dosage to prevent harmful side effects.

Synthesis and antiproliferative evaluation of novel 3,5,8-trisubstituted coumarins against breast cancer.

Aim: This study focused on designing and synthesizing novel derivatives of 3,5,8-trisubstituted coumarin. Results: The synthesized compounds, particularly compound 5, exhibited significant cytotoxic effects on MCF-7 cells, surpassing staurosporine, and reduced toxicity toward MCF-10A cells, highlighting potential pharmacological advantages. Further, compound 5 altered the cell cycle and significantly increased apoptosis in MCF-7 cells, involving both early (41.7-fold) and late stages (33-fold), while moderately affecting necrotic signaling. The antitumor activity was linked to a notable reduction (4.78-fold) in topoisomerase IIß expression. Molecular modeling indicated compound 5's strong affinity for EGFR, human EGF2 and topoisomerase II proteins. Conclusion: These findings highlight compound 5 as a multifaceted antitumor agent for breast cancer.

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Impact of Nanoencapsulated Rosemary Essential Oil as a Novel Feed Additive on Growth Performance, Nutrient Utilization, Carcass Traits, Meat Quality and Gene Expression of Broiler Chicken.

This study evaluated the effect of free and nanoencapsulated rosemary essential oil (REO) as an antibiotic alternative in broiler diets on growth performance, nutrient digestibility, carcass traits, meat quality and gene expression. Four hundred twenty day-old commercial broiler chicks (VENCOBB) were randomly allocated to seven dietary treatments, each having four replicates of fifteen chicks. The dietary treatments comprised control (CON) fed a basal diet only, AB (basal diet + 10 mg enramycin/kg), CS (basal diet + 150 mg chitosan nanoparticles/kg), REOF100 and REOF200 (basal diet + 100 mg and 200 mg free REO/kg, respectively), and REON100 and REON200 (basal diet + 100 mg and 200 mg nanoencapsulated REO/kg, respectively). Overall (7-42 d), REON200 showed the highest (p < 0.001) body weight gain (1899 g/bird) and CON had the lowest gain (1742 g/bird), while the CS, REOF100 and REOF200 groups had a similar gain, but lower than that of the AB and REON100 groups. Feed intake was not affected by dietary treatments. Overall, the feed efficiency increased (p = 0.001) by 8.47% in the REON200 group and 6.21% in the AB and REON100 groups compared with the CON. Supplementation of REO improved (p < 0.05) dry matter and crude protein digestibility, with the highest values in REON100 and REON200. Ether extract, crude fiber, calcium and phosphorus digestibility values showed no difference among the groups. The dressing, breast, thigh % increased (p < 0.05) and abdominal fat % decreased (p < 0.001) more in the REON200 group than with other treatments and CON. In breast meat quality, water holding capacity and extract reserve volume increased (p < 0.05) while drip loss and cholesterol content decreased (p < 0.05) in REON100 and REON200. No change was observed in the breast meat color among dietary treatments and CON. The REON100 and REON200 groups had reduced (p < 0.05) meat lipid peroxidation as depicted by the decreased levels of TBARS, free fatty acids and peroxide value compared to other treatments and CON. The expression of the Mucin 2, PepT1 and IL-10 genes was upregulated (p < 0.001) and TNF-α downregulated (p < 0.001) by dietary addition of REO particularly in the nanoencapsulated form compared with the CON. In conclusion, nanoencapsulated REO, especially at 200 mg/kg diet, showed promising results as an antibiotic alternative in improving the performance, nutrient digestibility, carcass traits, meat quality and upregulation of growth and anti-inflammatory genes.

Supplementation of Saussurea costus root alleviates sodium nitrite-induced hepatorenal toxicity by modulating metabolic profile, inflammation, and apoptosis.

Sodium nitrite (NaNO2) is a widely used food ingredient, although excessive concentrations can pose potential health risks. In the present study, we evaluated the deterioration effects of NaNO2 additives on hematology, metabolic profile, liver function, and kidney function of male Wistar rats. We further explored the therapeutic potential of supplementation with S. costus root ethanolic extract (SCREE) to improve NaNO2-induced hepatorenal toxicity. In this regard, 65 adult male rats were divided into eight groups; Group 1: control, Groups 2, 3, and 4 received SCREE in 200, 400, and 600 mg/kg body weight, respectively, Group 5: NaNO2 (6.5 mg/kg body weight), Groups 6, 7 and 8 received NaNO2 (6.5 mg/kg body weight) in combination with SCREE (200, 400, and 600 mg/kg body weight), respectively. Our results revealed that the NaNO2-treated group shows a significant change in deterioration in body and organ weights, hematological parameters, lipid profile, and hepatorenal dysfunction, as well as immunohistochemical and histopathological alterations. Furthermore, the NaNO2-treated group demonstrated a considerable increase in the expression of TNF-α cytokine and tumor suppressor gene P53 in the kidney and liver, while a significant reduction was detected in the anti-inflammatory cytokine IL-4 and the apoptosis suppressor gene BCL-2, compared to the control group. Interestingly, SCREE administration demonstrated the ability to significantly alleviate the toxic effects of NaNO2 and improve liver function in a dose-dependent manner, including hematological parameters, lipid profile, and modulation of histopathological architecture. Additionally, SCREE exhibited the ability to modulate the expression levels of inflammatory cytokines and apoptotic genes in the liver and kidney. The phytochemical analysis revealed a wide set of primary metabolites in SCREE, including phenolics, flavonoids, vitamins, alkaloids, saponins and tannins, while the untargeted UPLC/T-TOF-MS/MS analysis identified 183 metabolites in both positive and negative ionization modes. Together, our findings establish the potential of SCREE in mitigating the toxic effects of NaNO2 by modulating metabolic, inflammatory, and apoptosis. Together, this study underscores the promise of SCREE as a potential natural food detoxifying additive to counteract the harmful impacts of sodium nitrite.

ADAMTS-13 and HMGB1-induced oxidative stress in Taenia multiceps-infected animals.

This study investigated the cytotoxic effects of oxidative stress (OS), high mobility group box 1 (HMGB1), ADAMTS (A disintegrin and metalloproteinase with thrombospondin motifs), and neuropathology associated with coenurus cerebralis (Taenia multiceps). ADAMTS-13, HMGB1, glutathione reductase (GR), copper/zinc superoxide dismutase (Cu/Zn SOD), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) expression levels were studied. The study found that ADAMTS-13 (P < 0.005), HMGB1 (P < 0.005), GR (P < 0.005), Cu/Zn SOD (P < 0.005), and 8-OHdG (P < 0.005) levels were significantly higher in T. multiceps (c. cerebralis)-infected animals compared to healthy control animals. This study's most important finding was that HMGB1 up-regulation in neurons, endothelial cells, and glial cells can directly cause brain parenchymal destruction and that HMGB1-mediated oxidative stress plays a crucial role in the neuropathogenesis of coenurosis. The results also showed that increased levels of ADAMTS-13 may play a pivotal role in regulating and protecting the blood-brain barrier integrity and neuroprotection. These findings also suggest that ADAMTS-13 and HMGB1 compete in the prevention or formation of microthrombi, which was regarded as a remarkable finding. ADAMTS-13 and HMGB1 are valuable biomarkers for disease risk assessment, estimating host neuropathy following T. multiceps (c. cerebralis) exposure, and providing a new therapeutic target. This is the first study to show that HMGB1 and ADAMTS-13 are expressed in reactive cells and are associated with neuroimmunopathology in coenurosis.