Dunnett's Multiple Comparison Research Articles

Therapeutic effects of Artocarpus communis J.R.Forst. & G.Forst. Seeds on Letrozole-induced Polycystic Ovary Syndrome Wistar rats

BackgroundHerbal extracts are an effective treatment for polycystic ovarian syndrome (PCOS) and have been shown to improve insulin resistance, hyperandrogenism, sex hormones, ovulation, and PCOS symptoms. Artocarpus communis seed's potential effects on polycystic ovary syndrome (PCOS) have not been studied. PurposeThis research aims to investigate the beneficial effects of Artocarpus communis seeds on PCOS induced by letrozole in Wistar rats. MethodsTo induce PCOS, female Wistar rats weighing between 160g to 250g were administered letrozole (1 mg/kg) for 21 days. Subsequently, for 12 days, the rats were given the Artocarpus communis seed methanol extract, and its hexane, DCM, ethyl acetate and aqueous fractions (100 mg/kg body weight) and Clomiphene citrate (1 mg/kg body weight), a standard medication. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol levels were assessed using ELISA, and the expression of P53, insulin receptor substrate (IRS), type 2 17-HSD (17-HSD), fat mass and obesity-associated (FTO), and 11a-hydroxylase/17,20-desmolase (CYP11a) genes were investigated. The data were analyzed using one-way ANOVA, and a significance threshold of p<0.05 was set for Dunnett's Multiple Comparison Test. ResultsAdministration of the methanol extract of Artocarpus communis seed and its Hexane fraction led to a decrease in LH level and an increase in FSH and estradiol levels in the PCOS-induced animals. Furthermore, methanol extract, DCM, and ethyl acetate fraction normalize the expression of P53, insulin receptor substrate (IRS), type 2 17-HSD (17-HSD), fat mass and obesity-associated (FTO), and 11a-hydroxylase/17,20-desmolase (CYP11a) genes in PCOS rats cervix. ConclusionArtocarpus communis seed exhibited ameliorative effects on polycystic ovary conditions in Wistar rats, suggesting its potential use in the management of PCOS.

Sensory evaluation and chemical composition of Solanum nigrum and Solanum torvum herbal tea and spice.

Herbal teas are ingested for various purposes and by diverse populations across the globe. There is a growing recognition among individuals of the advantages associated with the use of this beverage, leading to a heightened demand for the manufacture of herbal tea derived from therapeutic plants. Spices on the other hand add flavour to food but could pose harm if it is high in phytates and oxalates. The objective of this study was to develop natural spices and herbal tea with health beneficial properties using Solanum nigrum and Solanum torvum berries. Herbal tea samples from S. nigrum were prepared by sorting berries, maceration, divided into two (fermenting at 18 °C and non-fermenting) and dried at 60 °C for 12 h in a hot oven. Spices from S. torvum and S. nigrum were prepared by removing the berries from the stalk, freeze-drying and smooth milling into fine powder. In addition, antinutrient, phytochemical and sensory evaluation studies were conducted on these spices and herbal teas. A nine-point hedonic scale was utilized for the purpose of conducting a consumer acceptability sensory evaluation test using 101 untrained panelists. Data was then analyzed by t-test, one-way analysis of variance (ANOVA) and the level of significance (p < 0.05) was assessed using Tukey's and Dunnett's multiple comparison tests. The panellists expressed a favourable perception towards Solanum nigrum unripe unfermented green herbal tea (6.65 ± 2.08) as compared to the other formulated teas due to the components working together in a way that produces a nice tea sample. Both Solanum nigrum and Solanum torvum spices contained various levels of catechins, saponins, flavonoids, oxalates, phytates and tannins comparable to literature. The herbal tea samples exhibited a range of catechin content, varying from 0.255 to 0.756 mg/g. The antioxidant activity of the various herbal tea samples ranged from 66.37 ± 0.24 to 78.53 ± 0.18 µg/mL GAE as determined by the DPPH free radical assay Fermented black herbal teas recorded higher total phenols (2.80 ± 0.09d), total flavonoids (21.84 ± 1.84c) and showed greater antioxidant activity (78.53 ± 0.18a) as compared to the unfermented green herbal teas. The process of fermentation resulted in a decrease in pH from 7.22 to 6.53 within a period of 12 h. The Total Titratable Acidity (TTA) grew as the fermentation period progressed, whereas the Total Soluble Solids (TSS) decreased. Phytates were the least antinutrients among the two Solanum species accounting for 0.02 mg/100 g and 0.03 mg/100 g in S. torvum berries (STBs) and (S. nigrum berries) SNBs respectively.

A universal urinary cell gene signature of acute rejection in kidney allografts

IntroductionAcute rejection (AR) undermines the life-extending benefits of kidney transplantation and is diagnosed using the invasive biopsy procedure. T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), or concurrent TCMR + ABMR (Mixed Rejection [MR]) are the three major types of AR. Development of noninvasive biomarkers diagnostic of AR due to any of the three types is a useful addition to the diagnostic armamentarium. MethodsWe developed customized RT-qPCR assays and measured urinary cell mRNA copy numbers in 145 biopsy-matched urine samples from 126 kidney allograft recipients. We determined whether the urinary cell three-gene signature diagnostic of TCMR (Suthanthiran et al., 2013) discriminates patients with no rejection biopsies (NR, n = 50) from those with ABMR (n = 28) or MR (n = 20) biopsies. ResultsThe urinary cell three-gene signature discriminated all three types of rejection biopsies from NR biopsies (P < 0.0001, One-way ANOVA). Dunnett's multiple comparisons test yielded P < 0.0001 for NR vs. TCMR; P < 0.001 for NR vs. ABMR; and P < 0.0001 for NR vs. MR. By bootstrap resampling, optimism-corrected area under the receiver operating characteristic curve (AUC) was 0.749 (bias-corrected 95% confidence interval [CI], 0.638 to 0.840) for NR vs. TCMR (P < 0.0001); 0.780 (95% CI, 0.656 to 0.878) for NR vs. ABMR (P < 0.0001); and 0.857 (95% CI, 0.727 to 0.947) for NR vs. MR (P < 0.0001). All three rejection categories were distinguished from NR biopsies with similar accuracy (all AUC comparisons P > 0.05). ConclusionThe urinary cell three-gene signature score discriminates AR due to TCMR, ABMR or MR from NR biopsies in human kidney allograft recipients.

Comparative study of the bronchodilator efficacy and adverse effects of salbutamol and hyoscine butylbromide in horses with severe asthma.

Salbutamol and hyoscine butylbromide (HBB) are commonly used bronchodilators in horses with severe asthma (SA). To compare the bronchodilation potency, duration, and adverse effects of salbutamol and HBB in SA. Six horses in exacerbation of SA. The effects of inhaled salbutamol (1000 μg) and HBB (150 mg, IV) were compared in a randomized, blinded, crossover experiment. Lung function, intestinal borborygmi and heart rate were assessed before and sequentially until 180 minutes after drug administration, and analyzed with 2-way repeated-measures ANOVA and Dunnett's multiple comparison tests. Both treatments caused a similar improvement in lung function. Pulmonary resistance and reactance returned to baseline values within 30 minutes after HBB administration, whereas salbutamol improved reactance until 180 minutes (mean improvement at 180 minutes of 0.040 Kpa/L/s, 95% CI = 0.004 to 0.076; P = .02 for salbutamol and of 0.009 Kpa/L/s, 95% CI = -0.028 to 0.045; P = .98 for HBB for the resistance at 3 Hz and of 0.040 Kpa/L/s, 95% CI = 0.007 to 0.074; P = .01 for salbutamol and of 0.009 Kpa/L/s, 95% CI = -0.024 to 0.042; P = .97 for HBB for the reactance at 7 Hz). From 5 to 30 minutes after HBB administration, the heart rate accelerated (mean increase of 3.3 beats per minute, 95% CI = -6.6 to 13.1; P = .92 for salbutamol, and of 13.0 beats per minute, 95% CI = 3.6 to 22.4; P = .002 for HBB at 30 minutes) and the gut sounds decreased (mean reduction of 1.3, 95% CI = -0.1 to 2.8; P = .09 for salbutamol and of 2.8 for the gastrointestinal auscultation score, 95% CI = 1.4 to 4.3; P < .0001 for HBB at 30 minutes). Both drugs have a similar bronchodilator potency but with a longer duration for salbutamol. Gastrointestinal and cardiovascular effects were noted only with HBB, suggesting the preferential use of salbutamol to relieve bronchoconstriction in horses with asthma.

Effects of simulated glyphosate drift to native prairie plants and canola-compatible Brassicaceae species of North Dakota, United States

This study evaluated effects to native plant and weedy Brassicaceae species growing in areas potentially affected by drift of glyphosate used with glyphosate-resistant canola (Brassica napus). Ten native grass and forb species were selected based on importance in prairie areas of North Dakota, US; and four introduced Brassicaceae species (Brassica juncea, Brassica nigra, Brassica rapa, and Sinapis arvensis ssp. arvensis) were selected based on their ability to cross with B. napus. Greenhouse-grown seedlings were treated with 0 (carrier control), 0.00056, 0.0032, 0.018 and 0.1 × a field application rate (FAR) of 829 g ha−1 acid glyphosate (g acid equivalent or a.e. ha−1), along with no spray plants; with each treatment repeated in two experiments. Shoot dry weight and height were measured 14 days after treatment, and data were subjected to analysis of variance or covariance followed by a Dunnett's multiple comparison test to obtain No-Observed-Adverse-Effect-Rates (NOAERs) for both parameters. A Weibull regression was used to obtain the rate producing a 25% reduction (ER25) for shoot dry weight or height for a limited number of species and experiment combinations. Based on NOAER values for both shoot dry weight and height, most native species had reductions in growth with 0.1 × FAR resulting in NOAERs of 0.018 × FAR for at least one experiment. Nassella viridula was the most sensitive native species, with a NOAER of 0.0032 × FAR for shoot dry weight and one experiment for height. The Brassicaceae species responded similarly to glyphosate as the native species, with NOAER values ranging from 0.0032 to 0.018 × FAR. Only four species had valid regression analyses for shoot dry weight or height resulting in ER25 values between 0.007 and 0.054 × FAR. Pascopyrum smithii and Schizachyrium scoparium were not affected by glyphosate as indicated by NOAER values. This study indicated that drift concentrations between approximately 0.003, but more commonly ≥0.1 × FAR (2.49 and 82.9 g ha−1 acid glyphosate, respectively) may affect the growth and potential competitiveness of selected native plant species, and Brassicaceae species sexually compatible with glyphosate-resistant B. napus in North Dakota.

Therapeutic role of miR-26a on cardiaorenal injury in mice model of angiotensin-II induced chronic kidney disease through inhibition of LIMS1/ILK pathway.

Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. We generated a microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t-test were used to analyze the data. Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.

Alteration of Neurotrophic Factors and Innervation in Extraocular Muscles of Individuals With Concomitant Esotropia.

To determine whether neurotrophic factors and innervation in extraocular muscles (EOMs) were altered in different types of concomitant esotropia, and to explore the possible association between neurotrophic factors and innervation of EOMs in humans. Patients with concomitant esotropia who required strabismus surgery were recruited from January to December 2022. Lateral rectus EOMs were obtained from patients, and controls were obtained from deceased organ donors. Immunofluorescence (IF) was performed to detect innervation of EOMs (neurofilament and synaptophysin), and immunohistochemistry (IHC) was used to detect the neurotrophic factors insulin-like growth factor-1 (IGF-1), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and neurotrophin-3 (NT-3). The positive IHC results were further verified using western blotting (WB). One-way ANOVA followed by a Dunnett's multiple comparison post hoc test was used for continuous variables and the χ2 test for categorical variables. Spearman correlation analysis was used for the correlation analysis. We collected lateral rectus EOM samples from acute and chronic types of concomitant esotropia and controls. Consistent with IHC, WB showed that IGF-1 was significantly increased in patients with acute acquired comitant esotropia or essential infantile esotropia compared with controls. In IF, synaptophysins were significantly increased only in acute acquired comitant esotropia compared with controls. Furthermore, Spearman correlation analysis showed that the correlation between IGF-1 and synaptophysin was borderline (P = 0.057) for patients with acute acquired comitant esotropia. Our study highlights the role of IGF-1 and altered innervation of EOMs in acute acquired comitant esotropia, suggesting that an effect of increased IGF-1 on nerve innervation may temporarily cause a compensatory increase in the strength of lateral rectus muscles.

Hypoglycemic, antidiabetic and toxicological evaluation of leaf extract of Xylopia parviflora (A. rich.) Benth

BackgroundAlmost all Xylopia species have a long history of being used therapeutically in China due to their potent antioxidant properties. Xylopia parviflora (X. parviflora) is a relatively novel plant comprised mainly of beta-pinene, which has a rich history in Chinese medicine and is a principal active constituent in numerous Chinese herbs such as Rakkyo, the Chinese onions, Huasi Baidu Fang and Ru Xiang which are all native to China. ObjectiveThe study evaluated the antidiabetic potentials of the methanol leaf extract of X. parviflora and its toxicity profile. MethodsA modified version of the OECD guidelines was used to conduct acute and sub-chronic toxicity tests on the plant extract. The extract's effects on glucose, haematological, and biochemical components were evaluated using standard procedures. Using glibenclamide (10 mg/kg) and distilled water as positive and negative controls, the extract was tested for its antidiabetic activity in diabetic rats with streptozotocin induction at 50, 150, and 300 mg/kg for 28 days. Furthermore, vital organs underwent histopathological examination. Analysis of Variance (ANOVA) and the Dunnett multiple comparison tests were used for the statistical analysis, with a significance level of p < 0.05 ResultsPreliminary phytochemical analysis of the leaf extract revealed the presence of tannins, flavonoids, saponins, alkaloids, terpenoids, deoxy-sugars, and anthraquinones. The extract's median lethal dose (LD50) was greater than 2000 mg/kg in mice. Although it significantly reduced blood glucose levels in normal rats at 150 and 300 mg/kg doses, it had no toxic effects on the haematological and biochemical components of the collected blood samples. The extract produced an antidiabetic, non-dose-dependent impact on day seven at all the tested doses in streptozotocin-induced rats. On days 14, 21, and 28, however, glibenclamide and extract activity at all tested doses were comparable. At 200 mg/kg, the extract did not affect the histology of the liver, brain, kidney, or pancreas, but at 400 and 800 mg/kg, it had a slight and severe impact on these organs, respectively. ConclusionAccording to the study's findings, X. parviflora has antihyperglycemic activity and is non-toxic at low doses but may be harmful at high doses.

Effects of Topoisomerase II alpha Inhibition on Oral Cancer Cell Metabolism and Cancer Stem Cell Function.

Topoisomerase IIα (TOP2A), is an enzyme involved in DNA replication, transcription, recombination, and chromatin remodeling and is found in a variety of cancers. However, the role of TOP2A regulation in oral cancer progression is not fully explained. We investigated the effect of TOP2A inhibition on cell survival, metabolism, and cancer stem cell self-renewal function in oral cancer cells. Oral carcinoma cell line SCC25 was cultured in complete DMEM/F12 media and treated with 5μM of Etoposide (Topoisomerase II inhibitor) for 48h. The critical parameters of cellular metabolism, including extracellular acidification rate (ECAR) and mitochondrial oxidative phosphorylation based on the oxygen consumption rate of cancer cells were assessed using Seahorse assay. Western blotting was performed to assess the proteins that are associated with proliferation (Survivin, IL-6) and cancer stem cell function (Oct4, Sox2) in cell lysates prepared from control and etoposide treated groups. Statistical analysis was performed using One-way ANOVA with Dunnett's multiple comparisons test. The protein expression of TOP2A was significantly (P<0.05) inhibited by etoposide. Additionally, TOP2A inhibition decreased the mitochondrial respiratory parameters including basal respiration, maximal respiration and ATP production. However, TOP2A inhibition has no impact on glycolytic function. Moreover, the proliferative marker survivin and IL-6 showed a significant (P<0.05) decrease after TOP2A inhibition. Conversely, the protein expression of cancer stem cell markers Oct-4 and Sox 2 were not altered. These results indicate that inhibition of TOP2A is more efficacious by decreasing the mitochondrial metabolic reprogramming and thereby downregulating the key anti-apoptotic and pro-survival mediators. Thus, TOP2A represents an ideal therapeutic target and offers a potential treatment strategy for OSCC.

The antimicrobial activity of an antiseptic soap against Candida Albicans and Streptococcus Mutans single and dual-species biofilms on denture base and reline acrylic resins.

To evaluate the effect of antiseptic soap on single and dual-species biofilms of Candida albicans and Streptococcus mutans on denture base and reline resins. Samples of the resins were distributed into groups (n = 9) according to the prevention or disinfection protocols. In the prevention protocol, samples were immersed in the solutions (Lifebuoy, 0.5% sodium hypochlorite solution and PBS) for 7, 14 and 28 days before the single and dual-species biofilms formation. Overnight denture disinfection was simulated. In the disinfection protocol, samples were immersed in the same solutions during 8 hours after the single and dual-species biofilms formation. Antimicrobial activity was analyzed by counting colony-forming units (CFU/mL) and evaluating cell metabolism. Cell viability and protein components of the biofilm matrix were evaluated using confocal laser scanning microscopy (CLSM). Data were submitted to ANOVA, followed by Tukey's post-test (α = 0.05) or Dunnett's T3 multiple comparisons test. In the prevention protocol, Lifebuoy solution effectively reduced the number of CFU/mL of both species. In addition, the solution decreased the cell metabolism of the microorganisms. Regarding disinfection protocol, the Lifebuoy solution was able of reduce approximately of 2-3 logs for all the biofilms on the denture base and reline resin. Cellular metabolism was also reduced. The images obtained with CLSM corroborate these results. Lifebuoy solution was effective in reducing single and dual-species biofilms on denture base and reline resins.

Voice Pathologies and the General Population’s Perception

To examine how the general population perceives voice pathology based on subjective qualities. Descriptive, cross-sectional, survey-based study. This is an IRB-approved Qualtrics survey on Amazon MTurk for respondents ages 18 and older. Ten subjects with voice pathologies supplied voice recordings of the Rainbow Passage to be assessed by the respondents. Respondents then assessed the voice conditions on perceived qualities of intelligence, leadership ability, and employability. One-way analysis of variance (ANOVA) and Dunnett's multiple comparison test with Sidak correction compared the mean scores of the samples (alpha=0.05). A total of 1754 responses were included in the final dataset. The female control voice was scored as more likely to be a Fortune 500 leader as well as more intelligent, friendly, attractive, and employable when compared to the female vocal fry and muscle tension dysphonia (MTD) recordings (P<0.0001). Conversely, the male MTD was the only male pathology that received a significantly lower score on friendliness, attractiveness, Fortune 500 leader status and employability than the male control (P=0.0102, P=0.0007, P=0.0338, and P=0.0039, respectively). This study demonstrates the more critical appraisal of voice pathologies of female patients compared to their male counterparts. People with voice disorders are perceived as being less successful, a disadvantage to potential leadership and career opportunities.

Tissue Stabilization, Bacterial Adhesion, and Stem Cell Viability in Trans-cinnamaldehyde-conditioned Dentin

IntroductionThis laboratory study aimed to evaluate the effect of trans-cinnamaldehyde (TC) conditioning on dentin tissue stabilization, bacterial adhesion, and stem cell toxicity. MethodsDentin beams (n = 204) from extracted human molars were demineralized in phosphoric acid and treated with TC (2.5, 5, and 7.5%), 50% ethanol-water mixture (vehicle control) or 2.5% glutaraldehyde (GA) (positive control) for 30 minutes. Demineralized but untreated specimens served as the negative control. After treatment, collagen crosslinking was characterized by measuring the elastic modulus (Er) and hardness (n = 5). Biodegradation resistance was examined by determining the loss of dry mass (n = 8), hydroxyproline release (n = 4) and scanning electron microscopy (n = 2), after exposure to bacterial collagenase. Inhibition of bacterial adhesion was investigated by colony counting assay (n = 12) and scanning electron microscopy (n = 2). Viability of stem cells of the apical papilla on TC-conditioned dentin was determined using the Cell Counting Kit-8 assay (n = 8). Data were statistically analyzed using one-way analysis of variance (ANOVA) test followed by Dunnett's multiple comparisons at a significance level of 5%. ResultsTC-conditioned dentin showed a concentration-dependent increase in Er and hardness. The Er and hardness of 5% and 7.5% TC-conditioned dentin were significantly greater than that of the negative control and vehicle control groups (P < .05). There was no significant difference in the biodegradation resistance between GA and 5% TC-conditioned dentin (P > .05). TC-conditioned dentin showed a well-preserved collagen fibril network with clear cross-banding, comparable to GA-conditioned dentin. All concentrations of TC inhibited bacterial adhesion on dentin, significantly greater than the negative control (P < .05). There was no reduction in viability of stem cells of the apical papilla viability on TC-conditioned dentin compared to the negative control (P > .05). ConclusionsTC conditioning stabilized the dentin and protected it from enzymatic degradation. TC prevented bacterial adhesion on the dentin but maintained stem cell viability.

Intra-articular triamcinolone acetonide injection results in increases in systemic insulin and glucose concentrations in horses without insulin dysregulation.

Corticosteroids are a commonly used, inexpensive intra-articular treatment for osteoarthritis which may increase the risk for laminitis in horses due, in part, to hyperinsulinaemia. Humans with metabolic syndrome experience increases in insulin and glucose concentrations post-injection, but responses in horses are unknown. To determine the effect of a single intra-articular (IA) dose of triamcinolone acetate (TA) on blood insulin and glucose concentrations. Before-after study. Ten horses with normal insulin regulation as assessed by an oral sugar test received 18 mg of TA into one middle carpal joint. Insulin and glucose concentrations were evaluated at baseline and 4, 6, 8, 24, 48, and 72 h following IA corticosteroid injection. Differences from baseline were evaluated using a repeated measures ANOVA with Dunnett's multiple comparison testing or a Friedman test with Dunn's correction (significant at p < 0.05). Mean ± SD blood insulin concentration post IA TA injection was increased at 6 h (15.8 ± 3.1 μIU/mL, p = 0.01), 24 h (23 ± 5.8 μIU/mL, p ≤ 0.001), and 48 h (29 ± 13 μIU/mL, p ≤ 0.01) compared to baseline (10 ± 12.3 μIU/mL), with the peak at 48 h. Median ± 95% CI blood glucose concentration post IA TA injection was increased at 6 h (112.7 ± 20.3 mg/dL, p = 0.006), 8 h (112.9 ± 21.4 mg/dL, p = 0.004), 24 h (122.6 ± 14.6, p ≤ 0.0001), and 48 h (123.5 ± 15.4 mg/dL, p ≤ 0.0001) compared to baseline (89.2 ± 6.6 mg/dL), with the peak at 48 h. Only horses with normal insulin regulation were evaluated. Blood insulin and glucose concentrations modestly increased for 48 h following IA TA.

An Experimental Study on the Analgesic Action of Padmak Agad

Padmak Agad is indicated in all types of Luta and Keet Visha. According to Acharya Vagbhatta, heaviness in head and eyes, coma, dizziness, dyspnoea, pain, swelling, fever, itching and anorexia are common symptoms of all Keeta Damsha. Several synthetic and plant origin analgesic are being tested for their efficacy and potency on different animal model including hot plate, tail flick, tail clip, cold pain, filament pain, tail immersion technique, acetic acid induced writhing test, formalin induced writhing test etc. Material and Methods: Tail clip model and Hot plate model were selected for the present study. Eighteen Swiss albino mice had been divided in to three groups each group contain six mice. First group was negative control group; second group was test drug group while third group was standard group. Test drug was given to the group 2 for 7 days O.D. Result: When we performed the tail clip test, response time of group 1, 2, 3 were 4.40±1.853, 14.07±9.309, 40.68±11.759 seconds respectively. In Hot Plate model, calculated response time of group 1, 2, 3 were 2.93±0.667, 5.46±0.911, 6.04±0.857 seconds respectively. When we used Dunnett's multiple comparisons test to compare the group 1 to group 2 and group 1 to group 3, there was statistically no significant role of test drug in tail clip model and hot plate model. Discussion and Conclusion: No effect of Padmak Agad is found in tail clip model. Padmak Agad is effective in hot plate model but not up to significant level.

Role of pelitinib in the regulation of migration and invasion of hepatocellular carcinoma cells via inhibition of Twist1

BackgroundOverexpression of Twist1, one of the epithelial-mesenchymal transition-transcription factors (EMT-TFs), is associated with hepatocellular carcinoma (HCC) metastasis. Pelitinib is known to be an irreversible epidermal growth factor receptor tyrosine kinase inhibitor that is used in clinical trials for colorectal and lung cancers, but the role of pelitinib in cancer metastasis has not been studied. This study aimed to investigate the anti-migration and anti-invasion activities of pelitinib in HCC cell lines.MethodsUsing three HCC cell lines (Huh7, Hep3B, and SNU449 cells), the effects of pelitinib on cell cytotoxicity, invasion, and migration were determined by cell viability, wound healing, transwell invasion, and spheroid invasion assays. The activities of MMP-2 and -9 were examined through gelatin zymography. Through immunoblotting analyses, the expression levels of EMT-TFs (Snail1, Twist1, and ZEB1) and EMT-related signaling pathways such as mitogen-activated protein kinases (MAPKs) and Akt signaling pathways were measured. The activity and expression levels of target genes were analyzed by reporter assay, RT-PCR, quantitative RT-PCR, and immunoblotting analysis. Statistical analysis was performed using one-way ANOVA with Dunnett's Multiple comparison tests in Prism 3.0 to assess differences between experimental conditions.ResultsIn this study, pelitinib treatment significantly inhibited wound closure in various HCC cell lines, including Huh7, Hep3B, and SNU449. Additionally, pelitinib was found to inhibit multicellular cancer spheroid invasion and metalloprotease activities in Huh7 cells. Further investigation revealed that pelitinib treatment inhibited the migration and invasion of Huh7 cells by inducing Twist1 degradation through the inhibition of MAPK and Akt signaling pathways. We also confirmed that the inhibition of cell motility by Twist1 siRNA was similar to that observed in pelitinib-treated group. Furthermore, pelitinib treatment regulated the expression of target genes associated with EMT, as demonstrated by the upregulation of E-cadherin and downregulation of N-cadherin.ConclusionBased on our novel finding of pelitinib from the perspective of EMT, pelitinib has the ability to inhibit EMT activity of HCC cells via inhibition of Twist1, and this may be the potential mechanism of pelitinib on the suppression of migration and invasion of HCC cells. Therefore, pelitinib could be developed as a potential anti-cancer drug for HCC.

Effects of Angiotensin-converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on the Immune System of Pseudomonas aeruginosa Challenged Hamsters

The severe cases of coronavirus disease 2019 observed in patients with hypertension and diabetes mellitus disease have created controversy as to why this was the case and the role of angiotensin receptor blockers (ARBs) and angiotensin enzyme inhibitors was not ruled out as a contributing factor. The objective of this study was to investigate the effects of angiotensin converting enzyme inhibitors (ACEIs) and ARBs on respiratory immunity. The study used a Syrian hamster as an animal model to study the effects of ARBs and ACEIs on the immune system of Pseudomonas aeruginosa-challenged hamsters; fever was a response variable. The hamsters were randomly separated into three groups of six. One group was administered enalapril, another with losartan, and the last group was administered water for 30 days. After 30 days, the hamsters were inoculated with 0.2 mL of 1.5 × 108 cfu/mL of P. aeruginosa. After 18 h from the inoculation time, the temperature was taken every 2 h for 36 h. The temperature in all groups ranged from 35.5°C to 37.2°C with an average of 36.1°C and there was no mortality recorded at the end of 14 days. The results were analyzed using Dunnett multiple comparisons analysis of variance using Statistical Package for the Social Sciences version 27. There were no significant differences in temperature between hamsters treated with enalapril or losartan and those treated with water (control). In addition, no hamster developed fever. In conclusion, enalapril and losartan may not negatively affect the respiratory immunity. Effects of ACEIs and ARBs on the immune system of P. aeruginosa challenged hamsters.

Investigating the synergistic potential of TRAIL and SAHA in inducing apoptosis in MOLT-4 cancer cells

IntroductionT-cell acute lymphoblastic leukemia is characterized by its fast progression rate and high complications. TRAIL can be used to trigger apoptosis in cancer cells with minimal effects on normal cells, but most of cancer cells develop resistance to this agent through various mechanisms. HDAC inhibitors like SAHA can be used to make cancer cells more susceptible to TRAIL-induced apoptosis. In this study, this hypothesis was tested on MOLT-4 cancer cell line. Materials and methodsThe cells were divided into six groups including the control group, TRAIL 50 nM, TRAIL 100 nM, SAHA 2 μM, SAHA 2 μM + TRAIL 50 nM, and SAHA 2 μM + TRAIL 100 nM. Apoptosis was evaluated by flowcytometry after 24, 48 and 72 h. The expression levels of c-flip, DR4, DR5, CHOP, NF-κB, STAT3, Akt, and PI3K genes were investigated by quantitative real-time PCR. Data were analyzed using two-way variance analysis with Tukey's and Dunnett's multiple comparisons tests, and statistical significance was defined as having a p-value less than 0.05. ResultsGroups exposed to the combination of SAHA with TRAIL demonstrated the maximum apoptosis in MOLT-4 cells by increasing the expression of DR4, DR5, and CHOP and decreasing the expression of c-flip, STAT3, PI3k, Akt, and NF-kB genes. ConclusionIt can be concluded that SAHA increases the sensitivity of MOLT-4 cells to TRAIL-mediated apoptosis, which can be used as a strategy to overcome resistance to TRAIL in leukemic patients.

Changes in blood pressure, oxygen saturation, hemoglobin concentration, and heart rate among low-altitude migrants living at high altitude (5380 m) for 360 days.

This article aimed to study the adjustment and adaptation of resting systolic blood pressure (SBP), diastolic blood pressure (DPB), oxygen saturation (SpO2 ), hemoglobin concentration ([Hb]), and heart rate (HR) in low-altitude migrants during a 1-year stay at high altitude. Our study enrolled 35 young migrants who were exposed to a hypoxia environment at 5380 m altitude on the Qinghai Tibetan Plateau between June 21, 2017, and June 16, 2018. We set 14-time points (the 1st-10th, 20th, 30th, 180th, and 360th day after arriving at 5380 m) for obtaining the measurements of resting SBP, DBP, HR, SpO2, and [Hb] and compared them with the control values recorded prior to migration. Variables with continuous data were summarized as means (SD). One-way repeated measures ANOVA without assuming sphericity was carried out to test whether the mean values (SBP, DBP, HR, SpO2 , and [Hb]) on different days were different significantly. Furthermore, Dunnett's multiple comparisons test was carried out to determine the time points whose values were significantly different from the control values. SBP and DBP were continually increasing within d1-3 and peaked on the 3rd day, then steadily declined from d3 to d30. SBP fell back to the control values on d10 (p > 0.05), and DBP fell back to the control values on d20 (p > 0.05). A significant decline occurred on d180 (p < 0.05). Both SBP and DBP were lower than the control values on d180 (p < 0.05), and this trend was maintained to d360. There were similar characteristics of HR and BP in the time course at HA. HR on d1-3 was increasing (p < 0.05) compared to the control values, after which it fell back to the control values on d180 (p > 0.05), and this trend was maintained to d360. SpO2 was the lowest on d1 and lower than the control value throughout the study at HA (p < 0.05). [Hb] increased after long-term exposure (180 and 360 days) to HA (p < 0.05). Our study continuously monitored lowlanders at 5380 m in Tibet, and is perhaps the only longitudinal study of migrants conducted at an altitude above 5000 m during a 1-year period. Our study provides new information on the adjustment and adaptation of [Hb], SpO2 , SBP, DBP, and HR in high-altitude plateau migrants during a 360-day stay at an altitude of 5380 m.

Antioxidant and Ameliorative Effects of Basella alba L. On Letrozole-Induced Polycystic Ovarian Syndrome in Rats

Basella alba L. (BA) is utilized in Nigeria to manage Polycystic Ovarian Syndrome (PCOS),&nbsp;according to an ethnobotanical study. However, this claim has not been supported by any scientific data. This study investigated the effect of the methanol leaf extract of the plant in alleviating polycystic ovary conditions in rats. The methanol extract of BA was subjected to a brine shrimp lethality assay. Total Phenolic Content (TPC), Total Flavonoid Content (TFC), and the DPPH assay were used to measure antioxidant activity. To induce PCOS in thirty female Wistar rats (180-200 g), letrozole (1 mg/kg) was used. For 15 days, BA leaf methanol extract (100 mg/kg body weight) and Clomiphene citrate (1 mg/kg body weight), a standard medication, were given. Microscopically, the ovaries underwent histopathological investigation. ELISA was used to assess luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol levels. One-way ANOVA was used to analyze the data, and P &lt; 0.05 was set as the threshold for Dunnett's Multiple Comparison Test. LC50 value for the extract was 17.29±0.15 μg/mL. The DPPH radical scavenging activity of the ethyl acetate fraction was the highest. When PCOS animals were given BA, the ovarian stroma was normal and the granular cells were leutinized. The level of estradiol increased but the level of LH was not significantly different between the BA-treated group (0.23±0.03 mIU/mL) and the untreated PCOS group (0.23±0.01 mIU/mL). Basella alba leaf displayed ameliorative effects on polycystic ovary conditions in rats. This support the use of this plant in the management of PCOS.

Understanding the Pathogenesis of Red Mark Syndrome in Rainbow Trout (Oncorhynchus mykiss) through an Integrated Morphological and Molecular Approach.

Red mark syndrome (RMS) is a widespread skin disorder of rainbow trout in freshwater aquaculture, believed to be caused by a Midichloria-like organism (MLO). Here, we aimed to study the pathologic mechanisms at the origin of RMS by analyzing field samples from a recent outbreak through gene expression, MLO PCR, quantitative PCR, and a histopathological scoring system proposed for RMS lesions. Statistical analyses included a One-Way Analysis of Variance (ANOVA) with a Dunnett's multiple comparisons test to assess differences among gene expression groups and a nonparametric Spearman correlation between various categories of skin lesions and PCR results. In short, the results confirmed the presence of a high quantity of 16S gene copy numbers of Midichloria-like organisms in diseased skin tissues. However, the number of Midichloria-like organisms detected was not correlated to the degree of severity of skin disease. Midichloria-like organism DNA was found in the spleen and head kidney. The spleen showed pathologic changes mainly of hyperplastic type, reflecting its direct involvement during infection. The most severe skin lesions were characterized by a high level of inflammatory cytokines sustaining and modulating the severe inflammatory process. IL-1 β, IL-6, IL-10, MHC-II, and TCR were upregulated in severe skin lesions, while IL-10 was highly expressed in moderate to severe ones. In the moderate form, the response was driven to produce immunoglobulins, which appeared crucial in controlling the skin disease's severity. Altogether our results illustrated a complex immune interaction between the host and Midichloria-like organism.