Exploring the NRF2/HO-1 and NF-κB Pathways: Spirulina Nanoparticles as a Novel Approach to Combat Diabetic Nephropathy.

Arthrospira platensis has been the subject of plentiful studies due to its purported health advantages; nevertheless, additional investigation is required to determine whether several chronic diseases may be treated or avoided with its nanoform. Therefore, we set out to examine A. platensis nanoparticles (SNPs) to protect against kidney impairment caused by Streptozotocin (STZ) in diabetic rats, precisely focusing on its effect and the cellular intracellular pathways involved. Male Wistar rats were assigned into four groups: Group 1 was set as control, comprising the normal rats; group 2 was administered SNPs (0.5 mg/kg BW, once/day) orally for 84 consecutive days; group 3, STZ-diabetic rats were injected with STZ (65 mg/kg BW); and group 4, in which the diabetic rats were treated with SNPs. After inducing diabetes in rats for 84 days, the animals were euthanized. The results disclosed that SNP treatment substantially (P < 0.05) improved the glucose and glycated hemoglobin levels (HbA1c %), insulin, C-peptide, and cystatin C deterioration in diabetic rats. Furthermore, SNP administration significantly lowered (P < 0.05) nitric oxide (NO) and malondialdehyde (MDA) levels in renal tissue and enhanced kidney function metrics, as well as improved the antioxidant capacity of the renal tissue. In addition, oral SNPs overcame the diabetic complications concerning diabetic nephropathy, indicated by downregulation and upregulation of apoptotic and antiapoptotic genes, respectively, along with prominent modulation of the antiangiogenic marker countenance level, improving kidney function. SNP modulated the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 (NRF2/HO-1) pathways and inhibited the nuclear factor-κB (NF-κB) expression, strengthening the SNP pathways in alleviating diabetic nephropathy. The histopathology results corroborated the obtained biochemical and molecular observations, suggesting the therapeutic potential of SNPs in diabetic nephropathy via mechanisms other than its significant antioxidant and hypoglycemic effects, including modulation of antiangiogenic and inflammatory mediators and the NRF2/HO-1 pathways.

A rare rotated, medially displaced fracture-dislocation of the medial clavicle - Case report and review of the literature.

Clavicle fractures combined with sternoclavicular joint dislocations are very rare injuries that need to be addressed quickly and treated effectively due to the altered biomechanics of the shoulder girdle as well as to the potential damages to the surrounding "noble" anatomical structures. A diagnostic and therapeutic algorithm for such injuries has not yet been established. Computer Tomography with 3D reconstruction should be the diagnostic gold standard. In case of a highly displaced fracture and/or dislocation in an active patient, surgical treatment is advised in order to obtain proper bone and joint healing with satisfactory functional outcomes as well as to protect the surrounding anatomical structures from potential damages. We present the case of an 18-year-old male, skeletally mature patient, who had a fall while snowboarding. Subsequently he was diagnosed with a very uncommon combination of a displaced medial clavicle fracture and complete posterior Sterno-Clavicular dislocation with 111° rotation of the sternoclavicular fragment. We opted for surgery, decided to use "off-label" a 2.5 V-plate Ulna plate long (Medartis®) and to associate this procedure with a Sterno-Clavicular arthrodesis with tape-augmentation to stabilize the SC joint; this treatment strategy resulted in a good clinical outcome without any remaining instability and satisfactory ROM. We collected this case to describe this seldom combination, to show our treatment strategy and to advocate the creation of a standardized diagnostic and therapeutic algorithm. X-rays, Computer Tomography images and intraoperative photos are presented.

Retraction to "Silver-Doped Cadmium Selenide/Graphene Oxide-Filled Cellulose Acetate Nanocomposites for Photocatalytic Degradation of Malachite Green toward Wastewater Treatment".

[This retracts the article DOI: 10.1021/acsomega.1c02667.].

Effect of coconut oil on growth performance, carcass criteria, liver and kidney functions, antioxidants and immunity, and lipid profile of broilers.

The aim of this study is to evaluate the beneficial effects of coconut essential oil on growth performance, carcass criteria, antioxidant status, and immune response of broiler chicks. A total of 192 un-sexed 7-days broiler chicks were divided into six treatment sets with four copies of 8 chicks per set. The groups were as follows: (1) basal diet (without additive), (2) basal diet plus 0.5 ml coconut essential oil/kg, (3) basal diet plus 1 ml coconut essential oil/kg, (4) basal diet plus 1.5 ml coconut essential oil/kg, (5) basal diet plus 2 ml coconut essential oil/kg and (6) basal diet plus 2.5 ml coconut essential oil/kg. The results showed that the most prevalent compound in coconut oil is 6-Octadecenoic acid (oleic acid) representing 46.44% followed 2(3H)-Furanone, dihydro-5-pentyl- (CAS) (11.36%), Hexadecanoic acid (CAS) (4.71%), and vanillin (2.53%). Dietary 1 and 1.5 ml of coconut oil improved significantly the body weight and gain of broiler chickens. Dietary supplementation of 1 ml of coconut oil improved significantly liver function compared to control and other treatment groups. The supplementation with 1 ml coconut oil significantly reduced TG and VLDL compared to control and other treatment groups, while no significant differences in TC, HDL, and LDL due to dietary coconut oil. The present findings showed that dietary coconut oil with 1 and 1.5 ml/kg feed improved significantly antioxidants status through increased antioxidant enzymes like SOD and GSH while decreasing significantly MDA levels compared to control and other treatment groups. Therefore, it was concluded that the diets of broiler chickens could be fortified with coconut oil with 1 or 1.5 ml to improve the growth, feed utilization, and antioxidant status of broiler chickens.

Citrus Waste as Source of Bioactive Compounds: Extraction and Utilization in Health and Food Industry.

The current research was conducted to extract the bioactive compounds from citrus waste and assess their role in the development of functional foods to treat different disorders. The scientific name of citrus is Citrus L. and it belongs to the Rutaceae family. It is one of the most important fruit crops that is grown throughout the world. During processing, a large amount of waste is produced from citrus fruits in the form of peel, seeds, and pomace. Every year, the citrus processing industry creates a large amount of waste. The citrus waste is composed of highly bioactive substances and phytochemicals, including essential oils (EOs), ascorbic acid, sugars, carotenoids, flavonoids, dietary fiber, polyphenols, and a range of trace elements. These valuable compounds are used to develop functional foods, including baked products, beverages, meat products, and dairy products. Moreover, these functional foods play an important role in treating various disorders, including anti-aging, anti-mutagenic, antidiabetic, anti-carcinogenic, anti-allergenic, anti-oxidative, anti-inflammatory, neuroprotective, and cardiovascular-protective activity. EOs are complex and contain several naturally occurring bioactive compounds that are frequently used as the best substitutes in the food industry. Citrus essential oils have many uses in the packaging and food safety industries. They can also be used as an alternative preservative to extend the shelf lives of different food products.

Cell Growth Inhibition, DNA Fragmentation and Apoptosis-Inducing Properties of Household-Processed Leaves and Seeds of Fenugreek (Trigonella Foenum-Graecum Linn.) against HepG2, HCT-116, and MCF-7 Cancerous Cell Lines.

Household processing of fenugreek seeds and leaves, including soaking, germination, and boiling of the seeds, and air-drying of the leaves, has improved the levels of human consumption of the bitter seeds and increased the shelf life of fresh leaves, respectively. The potential anticancer activity of either unprocessed or processed fenugreek seeds or leaves and the relative expression of pro-apoptotic and anti-apoptotic genes of the studied cancerous cell lines exposed to IC50 crude extracts was investigated to observe the apoptotic-inducing property of this plant as an anticancer agent. The protein expression of IKK-α and IKK-ß, as inhibitors of NF-KB which exhibit a critical function in the regulation of genes involved in chronic inflammatory disorders, were studied in the tested cancerous cell lines. In this study, the anticancer activity of household-processed fenugreek leaves and seeds against HepG2, HCT-116, MCF-7, and VERO cell lines was measured using an MTT assay. DNA fragmentation of both HepG2 and MCF-7 was investigated by using gel electrophoresis. RT-PCR was used to evaluate the relative expression of each p53, caspase-3, Bax, and Bcl-2 genes, whereas ELISA assay determined the expression of caspase-3, TNF-α, and 8-OHDG genes. Western blotting analyzed the protein-expressing levels of IKK-α and IKK-ß proteins in each studied cell line. Data showed that at 500 µg mL-1, ADFL had the highest cytotoxicity against the HepG2 and HCT-116 cell lines. Although, each UFS and GFS sample had a more inhibitory effect on MCF-7 cells than ADFL. Gel electrophoresis demonstrated that the IC50 of each ADFL, UFS, and GFS sample induced DNA fragmentation in HepG2 and MCF-7, contrary to untreated cell lines. Gene expression using RT-PCR showed that IC50 doses of each sample induced apoptosis through the up-regulation of the p53, caspase-3, and Bax genes and the down-regulation of the Bcl-2 gene in each studied cell line. The relative expression of TNF-α, 8-OHDG, and caspase-3 genes of each HepG2 and MCF-7 cell line using ELISA assays demonstrated that ADFL, UFS, and GFS samples reduced the expression of TNF-α and 8-OHDG genes but increased the expression of the caspase-3 gene. Protein-expressing levels of IKK-α and IKK-ß proteins in each studied cell line, determined using Western blotting, indicated that household treatments decreased IKK-α expression compared to the UFS sample. Moreover, the ADFL and SFS samples had the most activity in the IKK-ß expression levels. Among all studied samples, air-dried fenugreek leaves and unprocessed and germinated fenugreek seeds had the most anti-proliferative and apoptotic-inducing properties against human HepG2, MCF-7, and HCT-116 cell lines, as compared to the VERO cell line. So, these crude extracts can be used in the future for developing new effective natural drugs for the treatment of hepatocellular, breast, and colon carcinomas.

Correction to "Silver-Doped Cadmium Selenide/Graphene Oxide-Filled Cellulose Acetate Nanocomposites for Photocatalytic Degradation of Malachite Green toward Wastewater Treatment".

[This corrects the article DOI: 10.1021/acsomega.1c02667.].

Silver-Doped Cadmium Selenide/Graphene Oxide-Filled Cellulose Acetate Nanocomposites for Photocatalytic Degradation of Malachite Green toward Wastewater Treatment.

Silver-doped cadmium selenide/graphene oxide (GO) (Ag-CdSe/GO) nanocomposites have been synthesized, loaded in cellulose acetate (CA) to form Ag-CdSe/GO@CA heterostructure nanofibers, and characterized in terms of structural, morphological, photocatalytic properties, among others. The photocatalytic degradation of malachite green (MG) was estimated using cadmium selenide-filled CA (CdSe@CA), silver-doped cadmium selenide-filled CA (Ag-CdSe@CA), cadmium selenide/GO-filled CA (CdSe/GO@CA), and silver-doped cadmium selenide/GO-filled CA (Ag-CdSe/GO@CA) nanocomposite materials. The Ag-CdSe/GO@CA nanocomposites exhibit and retain an enhanced photocatalytic activity for the degradation of MG dye. This amended performance is associated with the multifunctional supporting impacts of GO, Ag, and CA on the composite structure and properties. The superior photocatalytic activity is related to the fact that both Ag and GO can act as electron acceptors that boost the separation efficiency of photogenerated carriers and the loading of the combined nanocomposite (Ag-CdSe@GO) on CA nanofibers, which can augment the adsorption of electrons and holes and facilitate the movement of carriers. The stability of Ag-CdSe/GO@CA nanocomposite photocatalysts demonstrates suitable results even after five recycles. This study establishes an advanced semiconductor-based hybrid nanocomposite material for efficient photocatalytic degradation of organic dyes.

Neurotoxic, Hepatotoxic and Nephrotoxic Effects of Tramadol Administration in Rats.

The current study was performed to study the tramadol HCL toxic effects on the brain, liver, and kidney of adult male rats. Forty male adult albino rats were divided into 4 groups; the first one was considered as a control group, the others were orally administrated with 25, 50, and 100 b.wt. representing therapeutic, double therapeutic, and 4 times therapeutic doses, respectively, of tramadol HCL daily for 1 month. Serum and brain, hepatic, and renal tissues were collected for biochemical and molecular investigations. Tramadol HCL resulted in a significant increase in the brain serotonin, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and malonyldialdehyde (MDA) levels with a significant decrease in the reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. At the same line, hepatic and renal 8-OHdG and MDA levels showed a significant increase with a significant decrease in reduced glutathione (GSH), CAT, and SOD activities. In addition, hepatic and renal function parameters including serum alanine amino transferase (ALT), aspartate amino transferase (AST), urea, and creatinine were increased in a dose-dependent manner. At the molecular levels, hepatic cytochrome P5402E1 (CYP2E1), renal Kidney Injury Molecule-1 (KIM-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) showed also a significant increase in the expression levels. Histopathological evaluation of the brain confirmed the above biochemical results. In conclusion, tramadol HCL induced neurotoxic, hepatotoxic, and nephrotoxic effects in a manner relative to its concentration by affecting brain serotonin levels and hepatic and renal function, with the production of DNA damage and oxidative stress.

Hormonal and molecular alterations induced by sub-lethal toxicity of zinc oxide nanoparticles on Oreochromis niloticus.

This study was carried out to determine the biochemical and molecular potential effects of Zn-ONPs sub-lethal toxicity on the hormonal profile of Oreochromis niloticus (O. niloticus). One hundred and fifty O. niloticus juvenile female were used in this experiment; Ninety for determination of LC50 and other 60 fish were divided into 3 groups with 20 fish each (two replicate in each group). Group I used as control group whereas other groups treated with 1/20 and 1/30 of LC50 respectively for 4 days. Serum, pituitary gland, hepatic, pancreatic and muscular tissues were obtained for hormonal and molecular evaluation. Serum growth hormone (GH), thyroid stimulating hormone (TSH), triiodothyronine (T3), tetraiodothyronine (T4), follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone and insulin hormones were significantly decreased with a significant increase in both Adrenocorticosteroid hormone (ACTH) and cortisol levels with no change in serum glucagon levels. On molecular levels there were a significant down regulation in transcriptional levels of GH, Insulin like growth factor I (IGF-I), insulin and Insulin receptor-A (IRA genes. These results suggested that, hormonal and molecular alterations can be used as an early biomarkers for Zn-ONPs toxicity in fish.

Nanocurcumin improved glucose metabolism in streptozotocin-induced diabetic rats: a comparison study with Gliclazide.

In the present study, the biochemical effect of nanocurcumin (nanoCUR) compared with Gliclazide (GLZ) on the diabetic rats was studied. Forty male albino rats (Sprague Dawley) weighted 110 ± 20 g were used. Rats were randomly separated into two groups. Control, received no treatment. Streptozotocin (STZ)-induced diabetic groups take 5 ml/kg of STZ in normal saline daily for 30 days, further divided into diabetic non-treated group, did not receive any treatment: diabetic group treated by nanoCUR, received 15 mg/kg/day of nanoCUR orally for 30 days; diabetic group treated by GLZ, received 2 mg/kg/day of GLZ for 30 days. The mean body weights of all rats were registered and serum samples were collected for determination of fasting blood glucose (FBG), insulin concentration, liver glucokinase (GK), and glycogen synthase (GS) activities. Liver tissues were collected for determination of mRNA expression of insulin (INS), insulin receptor A (IRA), glucokinase (GK), and glucose transporter 2 (GLUT2). The results revealed a significant reduction of body weight in diabetic rats, with no significant differences in nanoCUR and GLZ groups. There was a decline in FBG levels and significant elevation of INS levels, GK, and GS activities in diabetic rats received nanoCUR and GLZ. mRNA expression of INS, IRA, GK, and GLUT2 significantly upregulated in diabetic rats received nanoCUR and GLZ. The amazing observation was a non-significant difference in all measured parameters between nanoCUR and GLZ groups. In conclusion, nanoCUR is able to improve cellular uptake of glucose, the hepatic insulin signaling, and insulin sensitivity in diabetic rats. Its effect was similar to standard hypoglycemic drug (GLZ).

Panax ginseng improves glucose metabolism in streptozotocin-induced diabetic rats through 5' adenosine monophosphate kinase up-regulation.

5' AMP-activated protein kinase (AMPK), insulin receptors and transporters are distorted in diabetes mellitus. In this study, the effect of Panax ginseng was assessed on glucose manipulating enzymes activities and gene expression of AMPK, IRA and GLUT2 in streptozotocin-induced diabetic male rats. Forty male albino rats were randomly divided to four groups 10 rats of each, group I, normal control group (received saline orally); group II, normal rats received 200 mg/kg of Panax ginseng orally; group III, Streptozotocin (STZ) -induced diabetic rats and group IV, STZ-induced diabetic rats received 200 mg/kg of Panax ginseng orally. The duration of experiment was 30 days. Results showed the ability of Panax ginseng to induce a significant decrease in the blood glucose and increase in the serum insulin levels, hepatic glucokinase (GK), and glycogen synthase (GS) activities with a modulation of lipid profile besides high expression levels of AMPK, insulin receptor A (IRA), glucose transporting protein-2 (GLUT-2) in liver of diabetic rats. In conclusion, the obtained results point to the ability of Panax ginseng to improve the glucose metabolism in diabetic models.

Patient-controlled analgesia with and without transverse abdominis plane and rectus sheath space block in cirrhotic patients undergoing liver resection.

BACKGROUND AND AIMS: Optimal pain control can be a challenge in cirrhotic patients. The aim was to compare the analgesic efficacy and side effects of intravenous fentanyl patient-controlled analgesia (PCA) with and without bupivacaine boluses in transversus abdominis plane (TAP) and rectus sheath space (RSB) in cirrhotics undergoing liver surgery. MATERIAL AND METHODS: A double-blinded randomized controlled trial (n = 55, child's A) was conducted. Catheters were inserted surgically in TAP and rectal sheath space during surgical closure. Fentanyl PCA + TAP + RSB group (gp) (n = 30): (0.2 ml/kg of 0.25% bupivacaine, 8 hourly) was compared with fentanyl PCA gp (n = 25): [0.2 ml/kg of saline (placebo) injected in catheters 8 hourly] for 48 h postoperatively. Plasma bupivacaine was measured with an enzyme-linked immunosorbent assay at 10 min, 30 min, 1 h, 2 h, and 4 h after each injection and 30 min before next injection. RESULTS: Fentanyl consumption was reduced in (PCA + TAP + RSB) gp compared to PCA gp (Day 1: 325.4 ± 169.1 vs. 1034 ± 231.7, Day 2: 204.44 ± 62.9 vs. 481.6 ± 158.3 µg, P < 0.05). Both groups demonstrated effective pain control at rest [Visual Analog Scales (VAS) <3), but on movement pain control with bupivacaine was better (P < 0.05). Increased demand for rescue opioids was observed prior to next scheduled bupivacaine injection in 10/30 patients on Day 1 and 2/30 on Day 2, in association with a reduced bupivacaine serum levels compared to 10 min after injection (47.6 ± 22.7 vs. 93.6 ± 61.0 ng/ml, respectively, P < 0.05). Bupivacaine did not exceed referred toxic levels. CONCLUSION: Repeated bupivacaine TAP and RSB with PCA fentanyl improved pain control, reduced opioids demand with no toxicity. Time interval between injections needs to be reduced to avoid breakthrough pain.

Association of MHC IIA polymorphisms with disease resistance in Aeromonas hydrophila-challenged Nile tilapia.

The major histocompatibility complex (MHC) genes show high polymorphisms in vertebrates depending on animal immunity status. Herein, MHC class IIA gene in Aeromonas hydrophila-challenged Nile tilapia was screened for presence of polymorphisms using sequencing. Twelve nucleotides deletion polymorphism was determined with a PCR product size of 267 bp in the resistant fish and 255 bp in the control and susceptible/diseased fish. Additionally, a non-synonymous right frameshift c.712 T > G (P. 238 * > G) SNP was detected at the stop codon (*). SNP-susceptibility association analysis revealed that fish carrying GG genotype and allele G were high susceptible (risk) for A. hydrophila, and had lower immune response as indicated by significant reduction in non-specific immune parameters (total protein, globulin, IgM, phagocytic activity, phagocytic index, and lysosome activity) and mRNA level of MHC IIA, interleukin 1 beta (IL1ß), tumor necrosis factor alfa (TNFα), and toll-like receptor 7 (TLR7) in the spleen and head kidney. Thus, G allele could be considered as a risk (recessive or mutant) allele for c. 712 T > G (P. 238 * > G) SNP and so selection of Nile tilapia with protective allele (T) for this SNP could improve the disease resistant of the fish.

The evolving role of protein disulfide isomerase A3 in Egyptian bladder cancer patients.

BACKGROUND: Protein disulfide isomerase A3 (PDIA3), an endoplasmic reticulum protein, is expressed in bladder of BC patients. However, its role in BC has been elusive till now. OBJECTIVES: This study was conducted to assess whether PDIA3 gene expression was associated with increased odds of BC, in particular muscle-invasive BC (MIBC). METHODS: Ninety three patients underwent cystoscopy and bladder tumors were biopsied and histologically assessed. Data collected including: patient demographics and clinical characteristics. Biochemical markers: hypoxia inducible factor 1-alpha (HIF-1 α), interleukin 6 (IL-6), advanced oxidation protein products (AOPP), Malondialdehyde (MDA), 8-hydroxy 2-deoxyguanosine (8-OHdG), and reduced glutathione (GSH) and molecular marker PDIA3 gene expression were measured. RESULTS: According to the tumor grade and stage, 36 patients were found to have MIBC, 27 patients have non MIBC (NMIBC) and 30 patients have no bladder lesions (control group). PDIA3 gene expression level had the largest contribution to a multivariable model for predicting BC, which achieved 89.0% predictive accuracy. The AUC for discriminating MIBC significantly increased from 0.644 to 0.938 when biochemical markers were replaced by molecular PDIA3 marker in the final model. CONCLUSIONS: Using PDIA3 expression along with prior information of patient's age, bilharzial history with gross hematuria, can help clinicians predict BC, discriminate MIBC and decide consequently the most promising therapeutic management in Egyptian population.

Oxidative Stress in the Muscles of the Fish Nile Tilapia Caused by Zinc Oxide Nanoparticles and Its Modulation by Vitamins C and E.

The effects of zinc oxide nanoparticles (ZnONPs) on antioxidants in Nile tilapia muscles and the protective role of vitamins C and E were examined. Two hundred males of Nile tilapia were held in aquaria (10 fishes/aquarium). Fishes were divided into 5 groups: 40 fishes in each group; the first group was the control; the 2nd and 3rd groups were exposed to 1 and 2 mg/L of ZnONPs, respectively; and the 4th and 5th group were exposed to 1 and 2 mg/L of ZnONPs and treated with a (500 mg/kg diet) mixture of vitamin C and E mixture (250 mg/kg diet of each). Muscles were collected on the 7th and 15th day of treatments. Muscle malondialdehyde, reduced glutathione levels, superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GR), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) activities were measured after treatments. Relative quantification of SOD, CAT, GR, GPx, and GST mRNA transcripts was detected in the muscles. Results showed that MDA and GSH concentration; SOD, CAT, GR, GPx, and GST activities; and mRNA expression were significantly decreased in groups exposed to ZnONPs. Vitamins C and E significantly ameliorated the toxic effects of ZnONPs. In conclusion, vitamins C and E have the ability to ameliorate ZnONP oxidative stress toxicity in Nile tilapia.

Association of CYP19A1 gene polymorphisms with anoestrus in water buffaloes.

Cytochrome P450 aromatase (encoded by the CYP19A1 gene) regulates oestrogen biosynthesis and so plays an essential role in female fertility. We investigated the genetic association of CYP19A1 with the risk of anoestrus in Egyptian water buffaloes. A total of 651 animals (326 anoestrous and 325 cycling) were used in this case-control study. Using single-strand conformation polymorphisms and sequencing, four single nucleotide polymorphisms (SNPs) were detected; c.-135T>C SNP in the 5'UTR and three non-synonymous SNPs: c.559G>A (p. V187M) in Exon 5, c.1285C>T (p. P429S) and c.1394A>G (p. D465G) in Exon 10. Individual SNP-anoestrus association analyses revealed that genotypes (CC, AA and GG) and alleles (C, A and G) of the -135T>C, c.559G>A and c.1394A>G SNPs respectively were high risk for anoestrus. A further analysis confirmed that these three SNPs were in linkage disequilibrium. Additionally, haplotypes with two (TAG/122 and CAA/221) or three (CAG/222) risk alleles were significantly associated with susceptibility to anoestrus, lower blood levels of both oestradiol and antioxidant enzymes (superoxide dismutase, glutathione peroxidase (GPX) and catalase) and downregulated expression levels of CYP19A1, oestrogen receptor α and Gpx3 in the ovary, as well as increased serum level of malondialdehyde. This suggests the occurrence of a high incidence of oxidative ovarian damage and subsequently ovarian inactivity in buffaloes carrying risk alleles. Therefore, with this study we suggest the selection of buffaloes with protective alleles at these SNPs to improve the reproductive efficiency of the herd.

Rho-kinase inhibitors from adlay seeds.

Rho-kinase enzymes are one of the most important targets recently identified in our bodies. Several lines of evidence indicate that these enzymes are involved in many diseases and cellular disorders. ROCK inhibitors may have clinical applications for cancer, hypertension, glaucoma, etc. Our study aims to identify the possible involvement of Rho-kinase inhibition to the multiple biological activities of adlay seeds and provide a rationale for their folkloric medicines. Hence, we evaluated Rho-kinase I and II inhibitory activity of the ethanol extract and 28 compounds derived from the seeds. A molecular docking assay was designed to estimate the binding affinity of the tested compounds with the target enzymes. The results of our study suggest a possible involvement of Rho-kinase inhibition to the multiple biological activities of the seeds. Furthermore, the results obtained with the tested compounds revealed some interesting skeletons as a scaffold for design and development of natural Rho-kinase inhibitors.

Impact of terlipressin infusion during and after live donor liver transplantation on incidence of acute kidney injury and neutrophil gelatinase-associated lipocalin serum levels: A randomized controlled trial.

BACKGROUND AND AIM: Acute kidney injury (AKI) with liver transplantation (LT) is not uncommon. Impact of terlipressin infusion on AKI, hemodynamics, and plasma concentration of neutrophil gelatinase-associated lipocalin (NGAL) was studied. METHODS: Patients (n=50) were randomized (NCT02059460, USA) into two equal groups: terlipressin vs Controls. Terlipressin (1-4 µg/kg/h) was administrated for 5 days. Intraoperative transesophageal Doppler for hemodynamic management. Renal functions, peak portal vein blood flow velocity (PPV), and hepatic artery resistive index (HARI) were recorded. Plasma NGAL (pNGAL) was measured baseline, 2 and 24 hours postreperfusion. RESULTS: Hepatitis C virus (HCV) was the main etiology. Age, sex, model of end-stage liver disease (MELD), and renal functions were comparable. Postoperative AKI incidence and NGAL concentrations were comparable (P>.05) between terlipressin and controls groups (44% vs 48% and 112.5±9 vs 93.1±8 ng/mL), respectively, but intraoperative NGAL in both groups increased significantly 2 hours postreperfusion (P<.05). The three NGAL readings were comparable (P>.05) between AKI (n=23) and non-AKI developers (n=27). Mean arterial blood pressure (MAP) was maintained in both groups with less systemic vascular resistance (SVR) fluctuations with terlipressin. Median norepinephrine consumption was lower in terlipressin vs controls (8 vs 12 mg; P=.04). The PPV and HARI were not affected by terlipressin at any stage (P>.05). CONCLUSION: Postliver transplant AKI was not prevented by terlipressin use nor predicted by NGAL levels.

Melanogenesis inhibitors from Coix lacryma-jobi seeds in B16-F10 melanoma cells.

An adenine derivative, 9-ß-D-glucopyranosyl adenine, reported for the first time from a natural source, in addition to nine known compounds were isolated from the seeds of Coix lacryma-jobi. Their structures were elucidated based on extensive spectroscopic and chemical studies. The isolated compounds and the ethanol extract have been assayed for melanin inhibition using B16-F10 melanoma cell line. The results of our study suggested the potential use of Coix lacryma-jobi seeds as a skin whitening agent and reveal the seeds to be a rich source of important phytochemicals with melanogenesis inhibitory activity. Among the isolated compounds, coixol (2) and 2-O-ß-glucopyranosyl-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (8) exhibited potent melanogenesis inhibitory activity with no obvious melanocytotoxicity. The rest of the compounds showed weak to moderate activity.