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A high fructose diet is a major cause of diabetes and various metabolic disorders, including fatty liver. In this study, we investigated the effects of resveratrol and vitamin D (VitD) treatments on endoplasmic reticulum (ER) stress, oxidative stress, inflammation, apoptosis, and liver regeneration in a rat model of type 2 diabetes mellitus, namely, T2DM Sprague-Dawley rats. This T2DM rat model was created through a combination treatment of a 10% fructose diet and 40 mg/kg streptozotocin (STZ). Resveratrol (1 mg/kg/day) and VitD (170/IU/week) were administered alone and in combination to both the diabetic and control groups. Immunohistochemical staining was performed to evaluate PCNA, NF-κB, TNF-α, IL-6, IL-1β, GRP78, and active caspase-3 in liver tissue. The TUNEL method and Sirius red staining were used to determine apoptosis and fibrosis, respectively. G6PD, 6-PGD, GR, and GST activities were measured to determine oxidative stress status. We found that the expressions of cytokines (TNF-α, IL-6, and IL-1β) correlated with NF-κB activation and were significantly increased in the T2DM rats. Increased GRP78 expression, indicating ER stress, increased in apoptotic cells, enhanced caspase-3 activation, and collagen accumulation surrounding the central vein were observed in the T2DM group compared with the other groups. The combination VitD + resveratrol treatment improved antioxidant defense via increasing G6PD, 6-PGD, GR, and GST activities compared to the diabetic groups. We concluded that the combined administration of resveratrol with VitD ameliorates the adverse effects of T2DM by regulating blood glucose levels, increasing antioxidant defense mechanisms, controlling ER stress, enhancing tissue regeneration, improving inflammation, and reducing apoptosis in liver cells. In conclusion, this study indicates that the combination treatment of resveratrol + VitD can be a beneficial option for preventing liver damage in fructose-induced T2DM.

Verbascum L. species are mainly used for inflammatory diseases and against malaria in traditional medicine. Therefore, we aimed to assess the in vivo anti-inflammatory, antinociceptive, and in vitro antimalarial activity of Verbascum latisepalum Hub.-Mor., Scrophulariaceac. The active methanolic extract was fractionated and the anti-inflammatory activity of the fractions was evaluated using a carragecnan-induced hind paw edema model. In addition, ap-benzoquinone-induced abdominal constriction test was employed in mice for the assessment of antinociccptivc activity. Two saponin glycosides, ilwensisaponin A and C, and three iridoid glucosides, aucubin, catalpol, and ajugol, in addition to a phenylethanoid glycoside, verbascoside, were isolated from the active fraction. The possible mechanisms of action were evaluated through molecular docking studies. Antimalarial properties of the methanolic extract were also tested in vitro by the parasite lactate dehydrogenase assay against Plasmodium falciparum, but any activity was detected.

We report one retinoblastoma patient with dual ophthalmic arteries (also known as "double ophthalmic arteries") arising from the internal carotid artery which fuse with each other inside the orbit. The caudal ophthalmic artery with larger caliber originated from the cavernous segment of internal carotid artery and passed through the superior orbital fissure. The cranial and tiny one arose more cranially from the supraclinoid internal carotid artery and passed through the optic canal. After superselective catheterization, frank anastomosis was shown between two ophthalmic arteries and the central retinal artery arose from the cranial one. To the best of our knowledge, this case is the first observation of a dual ophthalmic artery with cavernous/supracavernous origins fusing with each other proven by superselective ophthalmic angiography. Whether there is an anastomosis between two ophthalmic arteries is important for deciding which artery to be selected for intraarterial treatment. In cases of retinoblastoma, detailed angiographic analysis may be essential to examine the orbital arterial system and to avoid unexpected complications during intraarterial chemotherapy.

Coronavirus Disease-19 (COVID-19) is a highly contagious infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The development of rapid antigen tests has contributed to easing the burden on healthcare and lifting restrictions by detecting infected individuals to help prevent further transmission of the virus. We developed a state-of-art rapid antigen testing system, named DIAGNOVIR, based on immune-fluorescence analysis, which can process and give the results in a minute. In our study, we assessed the performance of the DIAGNOVIR and compared the results with those of the qRT-PCR test. Our results demonstrated that the sensitivity and specificity of the DIAGNOVIR were 94% and 99.2%, respectively, with a 100% sensitivity and 96.97% specificity, among asymptomatic patients. In addition, DIAGNOVIR can detect SARS‑CoV‑2 with 100% sensitivity up to 5 days after symptom onset. We observed that the DIAGNOVIR Rapid Antigen Test’s limit of detection (LoD) was not significantly affected by the SARS‑CoV‑2 variants including Wuhan, alpha (B1.1.7), beta (B.1.351), delta (B.1.617.2) and omicron (B.1.1.529) variants, and LoD was calculated as 8 × 102, 6.81 × 101.5, 3.2 × 101.5, 1 × 103, and 1 × 103.5 TCID50/mL, respectively. Our results indicated that DIAGNOVIR can detect all SARS-CoV-2 variants in just seconds with higher sensitivity and specificity lower testing costs and decreased turnover time.

Type 2 Diabetes Mellitus is a chronic metabolic disease that causes endothelial damage and is an important risk factor for atherosclerosis. In the present study vitamin D3 supplementation in rats was used to determine the role of Osteoprotegerin (OPG)/Receptor activator kB ligand (RANKL) signalling in endothelial damage and changes in the expression levels of genes involved in this pathway. We hypothesized that vitamin D3 supplementation affects OPG and RANKL activity in the aorta. Diabetes was induced in rats via injections of 40 mg/kg of streptozotocin followed by a high fructose (10%) diet. Group 2 (healthy) and 4 (diabetic) received 170 IU/kg of vitamin D3 weekly for 5 weeks, while Group 1 (healthy) and 2 (diabetic) received sterile saline. The aortas of each group were collected to analyse mRNA expression using the real-time PCR method and also to evaluate magnesium and calcium levels using inductively coupled plasma mass spectrometry. Opg and Il-1b expression levels were significantly associated with both diabetes and vitamin D3 supplementation in the aortas of the study groups (p ≤ 0.05). Opg mRNA expression was also found to correlate with both Icam-1 and Nos3 mRNA expression levels (r = 0.699, p = 0.001 and r = 0.622, p = 0.003, respectively). In addition, when mineral levels in the aortic tissues were compared among all groups, it was found that the interaction of diabetes and vitamin D3 supplementation significantly affected Mg levels and Mg/Ca ratios. It is concluded that vitamin D3 supplementation has a modulatory effect on OPG/RANKL activity in the vessel wall by ameliorating endothelial damage in diabetes. This effect may contribute to the regulation of cytokine-mediated vascular homeostasis and mineral deposition in the aorta; therefore, further comprehensive studies are proposed to demonstrate this relationship.

Supercapacitors are becoming more popular in the field of energy storage day by day. Thanks to their superior features such as fast charge–discharge, high capacities, and stable structures. Especially, supercapacitors designed using biomass as the electrode material are more preferred in this field because they are cheap, abundant, environmentally friendly, high capacity, and have a long cycle life. In this study, two supercapacitor cells were developed using freshwater algae biomass. In the first stage, supercapacitor electrodes were prepared by Co-doped Chlorella vulgaris (Chl-Co), and in the second stage, electrodes were prepared by Co-doped to H3PO4-washed Chlorella vulgaris (Chl-Co-H3PO4). 6 M KOH solution was used as the electrolyte. Electrochemical characterization results of the electrodes were obtained very close to the ideal supercapacitor characteristic. The capacitance values of the Chl-Co electrode were measured as 80 F/g for 1 A/g, but after the activation by H3PO4, the capacitance rose to 169.7 F/g for 1 A/g. The produced electrodes are promising for energy storage in terms of environmental pollution, cost, stability, and capacity.

BackgroundThe multiplede novocopy number variant (MdnCNV) phenotype is described by having four or more constitutionalde novoCNVs (dnCNVs) arising independently throughout the human genome within one generation. It is a rare peri-zygotic mutational event, previously reported to be seen once in every 12,000 individuals referred for genome-wide chromosomal microarray analysis due to congenital abnormalities. These rare families provide a unique opportunity to understand the genetic factors of peri-zygotic genome instability and the impact ofdnCNV on human diseases.MethodsChromosomal microarray analysis (CMA), array-based comparative genomic hybridization, short- and long-read genome sequencing (GS) were performed on the newly identified MdnCNV family to identifyde novomutations includingdnCNVs,de novosingle-nucleotide variants (dnSNVs), and indels. Short-read GS was performed on four previously published MdnCNV families fordnSNV analysis. Trio-based rare variant analysis was performed on the newly identified individual and four previously published MdnCNV families to identify potential genetic etiologies contributing to the peri-zygotic genomic instability. Lin semantic similarity scores informed quantitative human phenotype ontology analysis on three MdnCNV families to identify gene(s) driving or contributing to the clinical phenotype.ResultsIn the newly identified MdnCNV case, we revealed eightde novotandem duplications, each ~ 1 Mb, with microhomology at 6/8 breakpoint junctions. Enrichment ofde novosingle-nucleotide variants (SNV; 6/79) andde novoindels (1/12) was found within 4 Mb of thednCNV genomic regions. An elevated post-zygotic SNV mutation rate was observed in MdnCNV families. Maternal rare variant analyses identified three genes in distinct families that may contribute to the MdnCNV phenomenon. Phenotype analysis suggests that gene(s) withindnCNV regions contribute to the observed proband phenotype in 3/3 cases. CNVs in two cases, a contiguous gene duplication encompassingPMP22andRAI1and another duplication affectingNSD1andSMARCC2, contribute to the clinically observed phenotypic manifestations.ConclusionsCharacteristic features ofdnCNVs reported here are consistent with a microhomology-mediated break-induced replication (MMBIR)-driven mechanism during the peri-zygotic period. Maternal genetic variants in DNA repair genes potentially contribute to peri-zygotic genomic instability. Variable phenotypic features were observed across a cohort of three MdnCNV probands, and computational quantitative phenotyping revealed that two out of three had evidence for the contribution of more than one genetic locus to the proband’s phenotype supporting the hypothesis ofde novomultilocus pathogenic variation (MPV) in those families.

With the increasing concerns about the safety of chemical synthetic substances being added to food products, companies are beginning to search for natural sources of antimicrobials. Because essential oils were proven to have antimicrobial properties, they can be used as food preservatives. The mixture of essential oils may have a more potent antimicrobial profile compared to any single essential oil. Hence, the purpose of this work was to determine the chemical composition and inhibitory effects of Origanum compactum L. and Mentha piperita L. (Lamiaceae) essential oils alone or in combination against Staphylococcus aureus ATCC 29,213 and Escherichia coli ATCC 25,922. It is the first time reporting a combination of these two essential oils to control foodborne pathogens type Escherichia coli and Staphylococcus aureus. The major constituents of O. compactum essential oil were determined as carvacrol, thymol, p-cymene, and α-terpinene. Regarding M. piperita essential oil, menthofuran, menthol, methyl acetate, 1,8 cineole, and β-pinene were the major compounds. The mixture of essential oils presented a strong synergistic effect against E. coli, decreasing the minimum inhibitory concentration (MIC) of O. compactum from 0.0625% to 0.015625% (v/v) and the MIC of M. piperita from 1% to 0.125% (v/v). It was concluded that a mixture of essential oils provides a better antimicrobial effect against tested bacteria than that of the essential oils alone.