Body Mass Research Articles

The potency of <i>Elaeocarpus grandiflorus </i>Leaf Extract as Anti-obesity: <i>in vivo </i>and <i>in silico</i> Study

The research aims to determine the effect of ethanol extract of Elaeocarpus grandiflorus leaves extract as anti-obesity by in vivo and silico computational models. The pre-and -post-tests were carried out on 20 female Wistar rats, divided into 4 groups. The control group (K) received no treatment and the experimental groups were treated with E. grandiflorus extract of 200 mg/kg BW (P1), 400 mg/kg BW (P2), and 800 mg/kg BW (P3) for 14 days. The body weight, abdominal circumference, and abdominal fat mass were measured on Day 1 and Day 15. The results showed differences in body weight (p=0.02), abdominal circumference (p=0.01), and abdominal fat mass (p=0.00). In silico exploration, bioactive compounds of rutin, orientin, luteolin, vitexin, iso orientin, isovitexin, kaempferol, and quercetin were identified, and targeted ELAVL1, IGF1R, CREB1, AKT1, and PIK3R1 of the AMPK signaling pathway that involved in the anti-obesity mechanism. The high binding affinity values was rutin-EVAL1 (-9.3), orientin-ELAVL1 (-8.3), and quercetin- IGFR1 (-8.2). It can be concluded that the ethanol extract of E. grandiflorus leaves has the potential to be developed as an anti-obesity agent.

Relationship between parasitism with milk yield and body weight of Mafriwal cattle

Mafriwal cattle have good characteristics, but parasitism effects on their production have never been explored. This study aimed to determine the relationship between phenotypic markers of parasitism, namely packed cell volume (PCV), peripheral eosinophils count (PEC), nematode eggs (EPG), and coccidia oocyst (OPG) with the milk yield and body weight of Mafriwal cattle. Fecal and blood samples were collected from 242 cattle between 2021 and 2022. PCV and PEC were obtained from blood samples, while EPG and OPG were obtained from fecal samples. PCR was conducted to identify haemoparasite species. Milk yield data and the body weight of calves were also recorded. Spearman’s rank correlation showed that body weight has a negative correlation with PCV (r=-0.4; P<0.01) and a positive correlation with PEC (r=0.39; P<0.01) in 2022. Multiple linear regression models were used to determine the effect of phenotypic markers and year of sampling on milk yield and body weight. The best models were selected based on the lowest Akaike Information Criterion. Milk yield decreased significantly (P<0.001) from 2021 to 2022. An increase in PEC led to a significant reduction (P<0.001) in milk yield. Conversely, body weight increased significantly (P<0.001) from 2021 to 2022 and an increase in PCV caused a significant (P<0.001) reduction in body weight. Elevated EPG and OPG led to significant (P<0.01) reductions in body weight but the interaction between EPG and OPG has a significant positive (P<0.001) impact on body weight. Overall, the findings suggest that milk yield and body weight of Mafriwal cattle were significantly affected by parasitism thus necessitating the implementation of parasite control approaches.

Effect of standardized ileal digestible arginine:lysine on growth performance of 6 to 13-kg nursery pigs.

Four hundred and eighty newly weaned pigs (PIC 337 × 1050; Genus, Hendersonville, TN) with an initial body weight (BW) of 6.20 ± 0.61kg were used in a dose-response study to investigate the impact of increasing standardized ileal digestible (SID) Arg:Lys on nursery pig growth performance. At weaning, pigs were placed into 48 pens with five barrows and five gilts per pen. Pens were randomly assigned to one of six dietary treatments. The experimental diets were formulated with increasing SID Arg:Lys, achieved by substituting corn starch, glycine, and L-alanine with L-arginine, resulting in SID Arg:Lys ranging from 45 to 145%. Diets were sub-limiting in SID Lys and exceeded all other essential amino acid requirements. The experimental diets were fed across two feeding phases from d 0 to 10 and 10 to 27, with adjustments made to account for the Lys requirement of the pigs. All pens were placed on a common diet for the remaining 14 days of the study to evaluate carryover effects. Pigs and feeders were weighed at the start and end of each phase to calculate average daily gain (ADG), average daily feed intake (ADFI), and feed efficiency (G:F). Data were analyzed according to a linear regression model, which included the linear and quadratic effects of SID Arg:Lys and initial BW. Pen was the experimental unit, and results were considered significant at P ≤ 0.05 and a tendency at 0.50 < P ≤ 0.10. From d 0 to 27, Arg:Lys tended to have a quadratic effect on ADFI (P = 0.058), where 97.00 ± 7.631% SID Arg:Lys maximized feed intake. Similarly, Arg:Lys had a quadratic impact on ADG (P = 0.046), where ADG was maximized at a SID Arg:Lys of 95.65 ± 7.165. Correspondingly, Arg:Lys had a quadratic effect on pig BW on d 27 (P = 0.014). These effects carried through the end of the study, where Arg:Lys quadratically impacted d 0 to 41 ADFI (P = 0.006), ADG (P = 0.077), and d 41 BW (P = 0.028). There was no evidence of an effect of SID Arg:Lys on G:F throughout the study (P ≥ 0.315). In conclusion, SID Arg:Lys quadratically impacted ADFI and ADG in 6 to 13kg nursery pigs, where ADFI was maximized at a SID Arg:Lys of 97.00% (95% CI [81.6, 112.4%]), and ADG was maximized at a SID Arg:Lys of 95.65% (95% CI [81.2, 110.1%]). Together, these data suggest that the SID Arg:Lys requirement of nursery pigs is at least 81%, based on the lower bounds of the 95% CI for maximum ADG and ADFI, and excessive Arg supplementation may negatively affect growth performance.

Ameliorative effects of gallic acid on tebuconazole–induced adverse effects in the cerebellum of adult albino rats: histopathological and immunohistochemical evidence

ABSTRACT Tebuconazole (TEB) is a common triazole sterol demethylation inhibitor fungicide utilized to manage a variety of diseases in crops like cereals, fruits, and vegetables. The aim of this work was to assess the effects of TEB on the structure of the cerebellum in adult albino rats and possible protective impact of co-administration of Gallic acid (GA). Four groups of forty adult male albino rats were randomly selected, and the rats in group I received corn oil through daily gavage for 4 weeks. Group II received GA dissolved in the normal saline at a dose of 100 mg/kg through daily gavage for 4 weeks, group III administered with TEB dissolved in corn oil at its acceptable daily intake dose (0.02 mg/kg body weight) through daily gavage for 4 weeks, group IV rats received both TEB and GA. For light microscopic, ultrastructural, and immunohistochemical investigations, cerebellar specimens were prepared. TEB exposure led to neuronal damage in the form of degenerated Purkinje cells with vacuolated cytoplasm, areas of lost Purkinje cells, the basket cells appeared vacuolated with degenerated neuropil, the granule cells clumped with congested areas between them, dilated cerebellar islands, weak positive bcl2 immunoreactions in the Purkinje cells, and numerous GFAP-positive astrocytes. GA mitigated TEB-mediated histological changes in the cerebellar cortex. We concluded that TEB caused Purkinje neurons in the rat cerebellar cortex to degenerate and undergo apoptosis. GA had a neuroprotective benefit against TEB toxicity in the rat cerebellar cortex.

Otolith morphometry and its role in determining the growth of Periophthalmus chrysospilos distributed in some coastal provinces in the Mekong Delta

This article first provided information on otolith shapes, the variation of otolith weight by sex, fish size, season, and sampling site, and the linear relationship between otolith weight and fish size. A total of 815 Periophthalmus chrysospilos specimens from Duyen Hai, Tra Vinh; Tran De, Soc Trang; Dong Hai, Bac Lieu; and Dam Doi, Ca Mau in the Mekong Delta ranged from 4.20 to 12.50 cm total length and from 1.26 to 16.88 g weight were analysed. The analysis results revealed that Ps. chrysospilos had a square otolith, deeply notched at the anterior apex and flat at the posterior apex. The weight of the left otolith showed a statistical difference according to survey factors, including gender, fish size, season, and sampling site. The otolith weight had a proportional relationship with to the total length, body weight, and head length of mudskippers (r2 =0.7~0.9), which meant that fish size could be predicted from the otolith weight and about 70-90% of the otolith weight of Ps. chrysospilos varied corresponded the growth of the fish.

Nipocalimab in Early-Onset Severe Hemolytic Disease of the Fetus and Newborn

BackgroundIn early-onset severe hemolytic disease of the fetus and newborn (HDFN), transplacental transfer of maternal antierythrocyte IgG alloantibodies causes fetal anemia that leads to the use of high-risk intrauterine transfusions in order to avoid fetal hydrops and fetal death. Nipocalimab, an anti–neonatal Fc receptor blocker, inhibits transplacental IgG transfer and lowers maternal IgG levels.MethodsIn an international, open-label, single-group, phase 2 study, we assessed treatment with intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) administered from 14 to 35 weeks’ gestation in participants with pregnancies at high risk for recurrent early-onset severe HDFN. The primary end point was live birth at 32 weeks’ gestation or later without intrauterine transfusions as assessed against a historical benchmark (0%; clinically meaningful difference, 10%).ResultsLive birth at 32 weeks’ gestation or later without intrauterine transfusions occurred in 7 of 13 pregnancies (54%; 95% confidence interval, 25 to 81) in the study. No cases of fetal hydrops occurred, and 6 participants (46%) did not receive any antenatal or neonatal transfusions. Six fetuses received an intrauterine transfusion: five fetuses at 24 weeks’ gestation or later and one fetus before fetal loss at 22 weeks and 5 days’ gestation. Live birth occurred in 12 pregnancies. The median gestational age at delivery was 36 weeks and 4 days. Of the 12 live-born infants, 1 received one exchange transfusion and one simple transfusion and 5 received only simple transfusions. Treatment-related decreases in the alloantibody titer and IgG level were observed in maternal samples and cord blood. No unusual maternal or pediatric infections were observed. Serious adverse events were consistent with HDFN, pregnancy, or prematurity.ConclusionsNipocalimab treatment delayed or prevented fetal anemia or intrauterine transfusions, as compared with the historical benchmark, in pregnancies at high risk for early-onset severe HDFN. (Funded by Janssen Research and Development; UNITY ClinicalTrials.gov number, NCT03842189.)

Effects of Moringa oleifera leaf extract on growth performance, blood hematology, immunity, carcass, and meat quality of Mae Hong Son chicken

Moringa oleifera is a nutrient-rich plant with a wide range of beneficial effects on chicken and chicken products. Mae Hong Son chickens, a variety of Thai native poultry, are renowned for their exceptional meat quality, distinct flavor, and remarkable tenderness. Therefore, this present study aimed to investigate the effects of Moringa oleifera leaf extract (MOLE) on growth performance, blood hematology and immunity, carcass, and meat quality of Mae Hong Son chickens, respectively. Briefly, 200 birds of Mae Hong Son chickens were subsequently divided into 4 groups, each containing 50 birds. They were fed for 16 weeks with different supplementary as follows: 1. Control group 2. Placebo (maltodextrin + microcrystalline cellulose PH101) 3. 2% of MOLE extract supplementation and 4. 4% of MOLE extract supplementation. The results showed that T4 achieved the best outcomes in terms of body weight and average daily gain, while also having the lowest total white blood cell (WBC) count and the highest ND HI titer at 12 weeks old (p &lt; 0.05). On the other hand, T1 had the highest fat percentage and thiobarbituric acid reactive substances (TBARS) values in both the thigh and breast (p &lt; 0.05). Additionally, the shear force of T1 was the lowest, both in the thigh and breast (p &lt; 0.05). In summary, the potential of MOLE could improve growth performance, hematological parameters, immune response, and meat quality in Thai native chicken production.

Bifidobacterium animalis subsp. lactis CCFM1274 relieved allergic asthma symptoms by modifying intestinal tryptophan metabolism in mice.

Approximately two-thirds of patients with asthma, a common inflammatory airway disease, are thought to present with allergies. Probiotics and tryptophan metabolites are becoming increasingly important in treating allergic asthma. This study aimed to identify potential probiotic strains and tryptophan metabolites that could alleviate asthma symptoms. Based on in vitro fermentation experiments, we evaluated variations in probiotic capacity to metabolize tryptophan. Of the eight tested strains, Bifidobacterium animalis subsp. lactis CCFM1274 produced relatively high levels of indole-3-carboxaldehyde (I3C). A mouse model of allergic asthma was established by oral administration of ovalbumin (OVA) and was subjected to oral administration of probiotics. The results demonstrated that treatment with CCFM1274 reduced the tendency for body weight loss and mortality in OVA-induced asthmatic mice. Ingestion of CCFM1274 improved the infiltration of perivascular and peribronchial inflammatory cells in the lung sections stained with hematoxylin and eosin (H&E). This outcome was accompanied by a reduction in the serum levels of OVA-specific immunoglobulin E (OVA-sIgE) and in the levels of IL-10 and IL-17 in the bronchoalveolar lavage fluid (BALF). The linear discriminant analysis effect size (LEfSe) of the gut microbiota showed that CCFM1274 increased the relative abundance of Bifidobacterium. In conclusion, CCFM1274 remodeled intestinal tryptophan metabolism in mice and contributed to the improvement of allergic asthma.

The dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist tirzepatide effects on body weight evolution, adiponectin, insulin and leptin levels in the combination of obesity, type 2 diabetes and menopause in mice.

Tirzepatide (Tzp), a novel dual agonist glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1, is approved for treating insulin resistance and obesity, and menopausal women consuming a high-calorie diet are a target to study the Tzp effect. Therefore, we aimed to allometrically scale body weight (BW) in Tzp-treated obese diabetic menopausal mice. Three-month-old C57BL/6 female mice had bilateral ovariectomy (Ovx) or a sham procedure and for 12 weeks were fed a control diet or a high-fat and high sucrose diet (n = 120/each group [control (C), obese diabetic (Od), Ovx (O), sham (S), Tzp (T)]). Tzp was subcutaneously administered (10 nmol/kg) or vehicle once a day for an additional 4 weeks. The analysis considered log-transformed data and the allometric equation log y = log a + b log x. Od and OdO showed more upward slopes than C and CO. In C, BW was non-allometric by T administration. Od and OdO showed slightly positive slopes (more prominent in OdO than Od). OdT and OdOT showed negative slopes, significant intercepts, and more robust Pearson coefficients than untreated ones. A potent drug effect was seen with BW allometric decline. Interactions between diet versus Ovx and diet versus Tzp affected weight gain. Diet versus Ovx versus Tzp affected food intake. A model was developed to show three usual factors observed in mature women. Notably, Tzp improved the metabolism and weight loss of OdO mice. Tzp-treated mice showed negative allometric BW across treatment time, which is a quantitative assessment that allows better comparison between results.

Adequate Dose of Levothyroxine for Thyroid-Stimulating Hormone Suppression after Total Thyroidectomy in Patients with Differentiated Thyroid Cancer.

The adequate dose of levothyroxine (LT4) for patients who have undergone total thyroidectomy (TT) for differentiated thyroid cancer (DTC) is uncertain. We evaluated the LT4 dose required to achieve mild thyroid-stimulating hormone (TSH) suppression in DTC patients after TT. The electronic medical records of patients who underwent TT for DTC and received mild TSH suppression therapy were reviewed. Linear regression analysis was performed to evaluate the association between LT4 dose (μg/kg) and an ordinal group divided by body mass index (BMI). We also evaluated the trend in LT4 doses among groups divided by BMI and age. In total, 123 patients achieved mild TSH suppression (0.1 to 0.5 mIU/L). The BMI variable was divided into three categories: <23 kg/m2 (n=46), ≥23 and <25 kg/m2 (n=30), and ≥25 kg/m2 (n=47). In the linear regression analysis, BMI was negatively associated with the LT4 dose after adjusting for age and sex (P<0.001). The LT4 doses required to achieve mild TSH suppression based on the BMI categories were 1.86, 1.71, and 1.71 μg/kg, respectively (P for trend <0.001). Further analysis with groups divided by age and BMI revealed that a higher BMI was related to a lower LT4 dose, especially in younger patients aged 20 to 39 (P for trend=0.011). The study results suggest an appropriate LT4 dose for mild TSH suppression after TT based on body weight in patients with DTC. Considering body weight, BMI, and age in estimating LT4 doses might help to achieve the target TSH level promptly.

Effect of different LED light colors on welfare, performance, some behavioral patterns, and blood parameters of Muscovy ducks

BackgroundThe current study was conducted to assess the impact of different LED light colors on welfare indicators in Muscovy ducks. These welfare parameters encompassed growth performance, specific behaviors, tonic immobility (TI), feather score, haematological, and serum biochemical parameters. Eighty-four healthy unsexed Muscovy ducklings aged two weeks were randomly assigned to four groups (3replicates/group; each replicate contains 7 birds) based on different LED light colors. The first group was raised under white light, the second under red light, the third under blue light, and the fourth under yellow light. To assess the impact of various LED light colors on welfare, growth performance indicators (body weight, body weight gain, feed intake, and feed conversion ratio) were measured. Behavioral patterns including feeding, drinking, standing, walking, sitting, feather pecking, and other activities were recorded. Tonic immobility test (TI) and feather condition scoring were conducted at 3, 6, and 10 weeks of age. At the end of the study blood samples were collected for hematological and serum biochemical analyses.ResultsThe results revealed that using blue, yellow, and red colors had no adverse effect on the final body weight of the ducks (P > 0.05). Unlike to red light, blue light significantly reduced feather pecking, TI time and cortisol concentrations and improved the feather condition score (P ≤ 0.05).ConclusionsThe current findings suggest that the application of blue light effectively improves welfare indices and has no detrimental impact on the growth performance of Muscovy ducks thereby positively contributing to their welfare.

Safety evaluation of Indocalamus Iatifolius McClure leaves based on acute toxicity, harmful metals, and 9 organochlorine residue determination

To investigate the safety of Indocalamu Iatifolius McClur leaves sold in the market, a study was conducted using Indocalamu Iatifolius McClur leaves randomly collected from an online store and a large supermarket. Acute toxicity experiments were performed on mice, and their body weight was monitored for 14 days after administration. After the observation period, blood samples were collected for biochemical analysis, and organ pathology was examined. Then, the content of copper (Cu), lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), and the residues of nine organochlorine pesticides in Indocalamu Iatifolius McClur leaves were measured according to the National Food Safety Standard (GB/T5009-2003) and the pesticide residue determination methods in the 2020 edition of the Chinese Pharmacopoeia. The results showed that the mice in the Indocalamu Iatifolius McClur leaves (online store) group experienced mortality and severe liver and lung damage. The levels of lead, cadmium, mercury, arsenic, and the nine organochlorine pesticides met the relevant standards and regulations. However, the copper content in the Indocalamu Iatifolius McClur leaves (online store) group was nearly 80 times higher than that in the supermarket group. Mice in the Indocalamu Iatifolius McClur leaves (supermarket) group remained healthy without any abnormalities, and the levels of harmful metals and organochlorine pesticides complied with the standards and regulations. The study suggests the need for regulatory policies and safety standards for the sale of Indocalamu Iatifolius McClur leaves.

PTER is a N-acetyltaurine hydrolase that regulates feeding and obesity.

Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1-3. In endogenous taurine metabolism, dedicated enzymes are involved in the biosynthesis of taurine from cysteine and in the downstream metabolism of secondary taurine metabolites4,5. One taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by stimuli that alter taurine or acetate flux, including endurance exercise7, dietary taurine supplementation8 and alcohol consumption6,9. So far, the identities of the enzymes involved in N-acetyltaurine metabolism, and the potential functions of N-acetyltaurine itself, have remained unknown. Here we show that the bodymassindexassociated orphan enzyme phosphotriesterase-related (PTER)10 is a physiological N-acetyltaurine hydrolase. In vitro, PTER catalyses the hydrolysis of N-acetyltaurine to taurine and acetate. In mice, PTER is expressed in the kidney, liver and brainstem. Genetic ablation of Pter in mice results in complete loss of tissue N-acetyltaurine hydrolysis activity and a systemic increase in N-acetyltaurine levels. After stimuli that increase taurine levels, Pter knockout mice exhibit reduced food intake, resistance to diet-induced obesity and improved glucose homeostasis. Administration of N-acetyltaurine to obese wild-type mice also reduces food intake and body weight in a GFRAL-dependent manner. These data place PTER into a central enzymatic node of secondary taurine metabolism and uncover a role for PTER and N-acetyltaurine in body weight control and energy balance.

SGLT-2 inhibitors and nephrolithiasis risk: a meta-analysis.

Sodium-glucose cotransporter (SGLT)-2 inhibitors are novel anti-diabetic medications with potential beneficial effects on cardiovascular and renal outcomes, metabolic parameters, and body weight. In addition to the beneficial effects on renal functions, including estimated glomerular filtration rate and reduction in proteinuria, recent studies have investigated the potential role of SGLT-2 inhibitor therapy on nephrolithiasis development. Nephrolithiasis, a condition affecting almost 10% of the general population at least once during a lifetime, is a common disorder with considerable risk for acute and chronic kidney injury and relatively few effective therapeutic options. We have performed a literature search through multiple databases, including PubMed, Ovid/Medline, Web of Science, Scopus, and Cochrane Library. We have followed the systematic review and meta-analysis guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses.We have included a total of 11635698 patients who experienced nephrolithiasis from six clinical trials to conduct this meta-analysis study. In the pooled analysis, nephrolithiasis occurred in 1,27% of patients from the SGLT2i group (n=739197), compared to 1,56% of patients (n=10896501) from the control arm (active control, placebo or no therapy). We have included a total of 11635698 participants who experienced nephrolithiasis from a total of six clinical studies with nephrolithiasis rates of 1,27% in the SGLT2i group (n=739197), compared to 1,56% in the control arm (n=10896501). SGLT-2 inhibitor therapy has been associated with a lower risk for nephrolithiasis compared to placebo (OR 0.61, 95% CI, 0.53-0.70, p<0.00001) or active therapy such as glucagon-like peptide 1 and dipeptidyl peptidase-IV inhibitors (OR 0.66, 95% CI, 0.47-0.93, p=0.02). We have demonstrated a lower risk of nephrolithiasis risk with SGLT-2 inhibitor therapy compared to placebo or active control. Potential underlying mechanisms include osmotic diuresis leading to a reduction in the concentration of lithogenic substances, anti-inflammatory and anti-fibrotic effects, and an increase in urine pH. There is a clear need for future large-scale randomized clinical trials evaluating such associations for better understanding.

Growth response of post weaned F1 Friesian × Borena (Bos taurus × Bos indicus) crossbred growing heifers fed on wheat straw-based densified complete feed block.

This experiment was designed to investigate the effect of feeding wheat-straw based densified complete feed block (DCFB) on daily weight gain, feed intake, digestibility and feed conversion rate in growing heifer calves. Eight weaned F1 Frisian*Borena (Bos taurus × Bos indicus) crossbred calves (92.5 ± 27.5kg body weight) and 5 months of age were randomly distributed into four groups, each with two animals evaluated under 4 × 4 double Latin Square Design for 240 days. The control treatment was natural pasture hay (NPH) and concentrate mix (CM) fed conventionally in a way that covers 50:50% requirements on dry matter (DM) bases and DCFB prepared by mixing wheat straw (WS) to concentrates mixture in the ratio of 50:50 (T2), 40:60 (T3) and 30:70 (T4), respectively. Each heifer group was fed on each diet for 60 days. At the end of each period the last 7 days were used to collect feed and feacal samples. However, the heifers were weighed each 15 days to estimate daily growth performances. It was found that significant (P < 0.05) differences among groups in average daily gain, feed conversion rate, feed intake and digestibility. The densification of WS and feeding in the form of feed block generally improved feed DM and nutrient intake and digestibility. The increase in the proportion of CM in the DCFBs also increased the DM and nutrient intake and digestibility. Heifer growth rate was higher (P < 0.05) in T1, T3 and T4 diets than T2 groups. Feed conversion ratio was higher (P < 0.05) both in T3 and T4 compared to T1 and T2. The total cost of production per each gram body weight gained was recorded higher (P < 0.05) for calves in the T2 group compared to calves in T1, T3 and T4. In conclusion, maintaining post weaned F1 heifer calves on DCFB composed of wheat straw and a commercial calf's concentrate based diet in the ratio of 40 to 60 would both biologically and economically feasible.

Determination of heavy metal concentration in African pike (Hepsetus odoe) from Alape River, Southwestern Nigeria

Aquatic ecosystems in Nigeria face significant environmental challenges because of anthropogenic activities, resulting in heavy metal contamination. Fish body weight and length and heavy metal concentrations in African pike (Hepsetus odoe) from Alape River, Igbokoda, Ilaje Local Government Area of Ondo State, Southwestern Nigeria, were investigated. Copper (Cu), Cadmium (Cd), Iron (Fe), Manganese (Mn), Nickel (Ni), and Lead (Pb) concentrations were measured in the gills, intestines, and trunks of the fish over six months (i.e., from May 2022 to October 2022) using an atomic absorption spectrophotometer (Buck Scientific’s 210VGP). Significant variations in heavy metal concentrations were observed across different months and organs. The order of concentrations for the six months, from highest to lowest, was Fe (2.26 mg/kg) > Ni (0.37 mg/kg) > Cu (0.23 mg/kg) > Mn (0.27 mg/kg) > Pb (0.05 mg/kg) > Cd (0.01 mg/kg). Higher concentrations were generally observed in the gills and intestines in May and June, whereas elevated levels were observed in the gills in September and October. These concentrations were compared with the maximum permissible limits established by the Food and Agriculture Organization and the World Health Organization for fish consumption, and all measured heavy metal concentrations were determined to be below the permissible limits. Body weight ranged from 172 to 362 g, and length ranged from 15.7 cm to 23.5 cm. The regression coefficient (b) ranged from − 0.134 to 0.204, indicating a relatively weak length–weight relationship. The condition factor (K) exhibited variations in the overall health and well-being of the fish. Based on these findings, the consumption of African pike from the Alape River is currently considered safe for humans, regardless of fish size, with all of the heavy metal concentrations within the permissible limits. However, continuous monitoring is crucial to ensure the ongoing safety of aquatic ecosystems and human health.

Electroacupuncture alleviates diabetes-induced mechanical allodynia and downregulates bradykinin B1 receptor expression in spinal cord dorsal horn.

Diabetic neuropathic pain (DNP) is one of the most prevalent symptoms of diabetes. The alteration of proteins in the spinal cord dorsal horn (SCDH) plays a significant role in the genesis and the development of DNP. Our previous study has shown electroacupuncture could effectively relieve DNP. However, the potential mechanism inducing DNP's genesis and development remains unclear and needs further research. This study established DNP model rats by intraperitoneally injecting a single high-dose streptozotocin; 2 Hz electroacupuncture was used to stimulate Zusanli (ST36) and Kunlun (BL60) of DNP rats daily from day 15 to day 21 after streptozotocin injection. Behavioral assay, quantitative PCR, immunofluorescence staining, and western blotting were used to study the analgesic mechanism of electroacupuncture. The bradykinin B1 receptor (B1R) mRNA, nuclear factor-κB p65 (p65), substance P, and calcitonin gene-related peptide (CGRP) protein expression were significantly enhanced in SCDH of DNP rats. The paw withdrawal threshold was increased while body weight and fasting blood glucose did not change in DNP rats after the electroacupuncture treatment. The expression of B1R, p65, substance P, and CGRP in SCDH of DNP rats was also inhibited after the electroacupuncture treatment. This work suggests that the potential mechanisms inducing the allodynia of DNP rats were possibly related to the increased expression of B1R, p65, substance P, and CGRP in SCDH. Downregulating B1R, p65, substance P, and CGRP expression levels in SCDH may achieve the analgesic effect of 2 Hz electroacupuncture treatment.

Genotypic and phenotypic characterisation of three local chicken ecotypes of Ghana based on principal component analysis and body measurements.

This study aimed to characterise three Ghanaian local chicken ecotypes, namely, Interior Savannah, Forest, and Coastal Savannah, based on morphological data and single nucleotide polymorphism (SNP) genotypes. Morphological data including body weight, shank length, body girth, back length, thigh length, beak length, comb length, and wattle length were collected from 250 local chickens. DNA isolated from blood of 1,440 local chickens was used for SNP genotyping with the Affymetrix chicken 600k SNP chip. Principal component analysis showed that Forest and Coastal Savannah birds were closely related. Generally, all three ecotypes exhibited high genetic diversity, especially birds from the Interior Savannah zone. Morphological characterisation showed that ecotype (p = 0.016) and sex (p = 0.000) had significant effects on body weight. Birds of the Interior Savannah ecotype were the heaviest (p = 0.004), with mean weights of 1.23 kg for females and 1.40 kg for males. Sex also had a strong significant effect on most of the morphological measurements, but the sex * ecotype interaction effect was not significant. Very few of the feather phenotypes previously reported to be associated with heat resistance-frizzle (2%) and naked neck (1.6%)-were found in the studied populations. It is concluded that the three local ecotypes are genetically diverse but with similar morphological features and the information provided would be useful for future selection decisions.

Blocking CTLA-4 promotes pressure overload-induced heart failure via activating Th17 cells.

Targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) with specific antibody offers long-term benefits for cancer immunotherapy but can cause severe adverse effects in the heart. This study aimed to investigate the role of anti-CTLA-4 antibody in pressure overload-induced cardiac remodeling and dysfunction. Transverse aortic constriction (TAC) was used to induce cardiac hypertrophy and heart failure in mice. Two weeks after the TAC treatment, mice received anti-CTLA-4 antibody injection twice a week at a dose of 10 mg/kg body weight. The administration of anti-CTLA-4 antibody exacerbated TAC-induced decline in cardiac function, intensifying myocardial hypertrophy and fibrosis. Further investigation revealed that anti-CTLA-4 antibody significantly elevated systemic inflammatory factors levels and facilitated the differentiation of T helper 17 (Th17) cells in the peripheral blood of TAC-treated mice. Importantly, anti-CTLA-4 mediated differentiation of Th17 cells and hypertrophic phenotype in TAC mice were dramatically alleviated by the inhibition of interleukin-17A (IL-17A) by an anti-IL-17A antibody. Furthermore, the C-X-C motif chemokine receptor 4 (CXCR4) antagonist AMD3100, also reversed anti-CTLA-4-mediated cardiotoxicity in TAC mice. Overall, these results suggest that the administration of anti-CTLA-4 antibody exacerbates pressure overload-induced heart failure by activating and promoting the differentiation of Th17 cells. Targeting the CXCR4/Th17/IL-17A axis could be a potential therapeutic strategy for mitigating immune checkpoint inhibitors-induced cardiotoxicity.

Nedosiran population pharmacokinetic and pharmacodynamic modelling and simulation to guide clinical development and dose selection in patients with primary hyperoxaluria type 1.

To characterize pharmacokinetic and pharmacodynamic profiles of nedosiran in patients with primary hyperoxaluria type 1 (PH1), identify influential covariates and confirm therapeutic doses. A population pharmacokinetic (PK)/pharmacodynamic (PD) (POP-PKPD) model was developed to characterize the concentration-time course of nedosiran and the corresponding effect on 24-h urinary oxalate (Uox). Simulations of dosing to achieve clinically meaningful reduction in Uox in children, adolescents and adults with PH1 were performed. Analyses included PK data from 143 healthy participants and PH1/PH2 patients, and PD data from 46 PH1 patients. Nedosiran PK was described by a two-compartment model with dual n-transit absorption and parallel linear and nonlinear elimination. The relationship between nedosiran exposure and Uox was described by an indirect response model. Body weight, estimated glomerular filtration rate (eGFR) and disease status were identified as influential covariates for the POP-PK model. The simulation results supported a weight-banded dosing regimen of nedosiran sodium in adolescents and adults (≥12 years) with PH1 of 170 mg (weight ≥50 kg) and 136 mg (weight <50 kg), in children (6-11 years) with PH1 of 3.5mg/kg, and no dose adjustments for PH1 patients with relatively preserved kidney function (eGFR ≥ 30 mL/min/1.73m2). Following the proposed dosing regimens, the simulated median fold-changes in PK AUC0-τ,ss were acceptable (≤1.51 fold-change) and ~71% of PH1 patients across all age groups achieved near-normal Uox (<0.6mmol) by week 52. The final POP-PKPD model characterizes observed nedosiran PK and Uox data. Simulations support nedosiran dosing regimens in PH1 patients aged ≥6years with relatively preserved kidney function.