Exploration of the protective mechanisms of Icariin against cisplatin-induced renal cell damage in canines.

This study delves into the protective mechanisms of Icariin (ICA) against cisplatin-induced damage in Madin-Darby canine kidney (MDCK) cells. Comprising two distinct phases, the investigation initially employed a single-factor randomized design to ascertain the minimal cisplatin concentration eliciting MDCK cell damage, spanning concentrations from 0 to 16 mmol/L. Concurrently, various concentrations of ICA (ranging from 5 to 50 mmol/L) were combined with 1 mmol/L cisplatin to determine the most efficacious treatment concentration. Subsequent investigations utilized four treatment groups: control, 1 mmol/L cisplatin, 1 mmol/L cisplatin + 20 mmol/L ICA, and 1 mmol/L cisplatin + 25 mmol/L ICA, aimed at elucidating ICA's protective mechanisms. Findings from the initial phase underscored a significant reduction in MDCK cell viability with 1 mmol/L cisplatin in comparison to the control (P < 0.01). Notably, the inclusion of 20 and 25 mmol/L ICA substantively ameliorated MDCK cell viability under 1 mmol/L cisplatin (P < 0.01). Moreover, cisplatin administration induced an elevation in inflammatory factors, malondialdehyde (MDA), reactive oxygen species (ROS), and Bax protein levels, while concurrently suppressing superoxide dismutase (SOD), catalase (CAT), and Bcl-2 expression (P < 0.01). Conversely, supplementation of 20 and 25 mmol/L ICA demonstrated a marked increase in mitochondrial membrane potential and levels of SOD, CAT, and Bcl-2 (P < 0.01). These interventions effectively attenuated inflammatory responses and suppressed Bax protein expression (P < 0.05), consequently mitigating cisplatin-induced apoptosis in MDCK cells (P < 0.01). In summary, these findings elucidate the role of ICA in impeding apoptosis in cisplatin-induced MDCK cells by regulating inflammatory responses, oxidative stress, and autophagic protein expression.

The age-related metabolizable energy of cereal grains, oilseed meals, corn gluten meals, and feather meals for broilers.

A 2 × 3 factorial arrangement of treatments with two ages of broilers (11 to 14 or 25 to 28 d of age) and three samples of feed ingredients was utilized to compare metabolizable energy (ME) and ratio of ME to gross energy (GE) in each group of three cereal grains (CG, including one corn, two wheat flour), three oilseed meals (OM, including one soybean meal, one peanut meal, and one cottonseed meal), three corn gluten meals (CGM A, B, and C), and three feather meals (FM A, B, and C). Each treatment contained six replicates of four Arbor Acre male broilers in energy balance experiments. Trends toward interactions between age and source of CG were observed on the ME and ME/GE of CG (0.05

Databases lack true information on metabolizable energy (ME) values of feed ingredients for broilers across phases. The current study evaluated the effect of broiler age (11 to 14 d or 25 to 28 d) on ME of three cereal grains (CG, one corn, two wheat flour [WF]), three oilseed meals (OM, one soybean meal, one peanut meal, and one cottonseed meal), three corn gluten meals (CGM, three sources of CGM differed in crude protein content), and three feather meals (FM, one enzymatical hydrolyzed FM, one expanded FM, and one hydrolyzed FM). Our study demonstrated no interactive effects between broiler age and source of feed on ME of OM and FM, but detected interactive effects for CG and CGM. Thus, the effect of age on ME can depend on the type of feed and its chemical composition. In addition, the ME of WF and OM was not affected by age, but the ME of corn, CGM, and FM increased as broilers aged. These results indicate that the ME in starter diets with corn, CGM, and FM may be overestimated if the ME values of feed ingredients are obtained from growing broilers.

An automatically progressed computer-controlled simulated digestion system to predict digestible and metabolizable energy of unconventional plant protein meals for growing pigs.

The objective of this experiment was to develop a new computer-controlled simulated digestion system to predict the digestible energy (DE) and metabolizable energy (ME) of unconventional plant protein meals for growing pigs. Nine meals tested included 1 source of rapeseed meal, 4 sources of cottonseed meal, 2 sources of sunflower meal, and 2 sources of peanut meal. Twenty growing pigs (Duroc × [Landrace × Large White]) with an initial body weight (BW) of 41.7 ± 2.6 kg were allotted to a replicated 10 × 3 incomplete Latin square design to determine the DE and ME of 1 basal diet and 9 experimental diets formulated with 9 unconventional plant protein meals. The DE and ME values of unconventional plant protein meals were calculated by the difference method. The in vitro digestible energy (IVDE) of 1 basal diet, 9 experimental diets, and 9 unconventional plant protein meals were determined with 5 replicates of each sample in a complete randomized arrangement. The IVDE/DE or IVDE/ME ranged from 0.96 to 0.98 or 1.00 to 1.01, and the correlation coefficient between IVDE and DE or ME was 0.97 or 0.98 in 10 experimental diets. Accordingly, the IVDE/DE or IVDE/ME ranged from 0.86 to 1.05 or 0.96 to 1.20, and the correlation coefficient between IVDE and DE or ME was 0.92 or 0.91 in 9 unconventional plant protein meals. The coefficient of variation (CV) of IVDE was less than that of DE and ME in the experimental diets (0.43%, 0.80%, and 0.97% for CV of IVDE, DE and ME, respectively) and unconventional plant protein meals (0.92%, 4.84%, and 6.33% for CV of IVDE, DE and ME, respectively). The regression equations to predict DE from IVDE in 10 experimental diets and 9 unconventional plant protein meals were DE = 0.8851 × IVDE +539 (R 2 = 0.9411, residual standard deviation [RSD] = 23 kcal/kg DM, P < 0.01) and DE = 0.9880 × IVDE + 166 (R 2 = 0.8428, RSD = 182 kcal/kg DM, P < 0.01), respectively. There was no statistical difference in the slopes (P = 0.82) or intercepts (P = 1.00) of these 2 equations. Thus, 10 diets and 9 unconventional plant protein meals were pooled to establish the regression equation of DE on IVDE as: DE = 0.9813 × IVDE +187 (R 2 = 0.9120, RSD = 118 kcal/kg DM, P < 0.01). The regression equations to predict ME from IVDE in 10 experimental diets and 9 unconventional plant protein meals were ME = 0.9559 × IVDE +146 (R 2 = 0.9697, RSD = 18 kcal/kg DM, P < 0.01) and ME = 0.9388 × IVDE + 3 (R 2 = 0.8282, RSD = 182 kcal/kg DM, P < 0.01), respectively. There was no statistical difference in slopes (P = 0.97) but significant difference between the intercepts (P = 0.02) of these 2 equations. Our results indicate IVDE has similar response to the DE but different response to the ME in 10 experimental diets and 9 unconventional plant protein meals. Therefore, IVDE is more suitable to predict DE than ME of diets and unconventional plant protein meals for growing pigs.

A comparative evaluation on the energetic values and digestibility of fatty acids in rice bran oil and palm oil for broilers.

The objective of this study was to compare the digestibility of energy and fatty acids (FA) in rice bran oil (RBO) and palm oil (PO) fed to growing Arbor Acre (AA) broilers. A corn-soybean meal basal diet and the basal diet supplemented with 8% RBO or PO were evaluated. A total of 72 AA male broilers (initial BW = 1,173 ± 6 g; age = 22 d) were randomly divided to 3 dietary treatments with 6 replicates of 4 broilers in each. The growth performance and the ME and FA digestibility in oils were compared with a balance experiment of broilers from d 22 to 28. The ME of the RBO diet was greater (P < 0.05) than PO diet and basal diet, and the ME of the PO diet was greater (P < 0.05) than basal diet. However, no statistical difference was observed in the ME intake of broilers fed basal, RBO, and PO diets. To maintain daily ME intake, broilers ingested more basal diet relative to other diets, resulting in increased CP intake (P < 0.01) and retention (P < 0.01) than broilers fed diets supplemented with RBO and PO. This finding resulted in greater (P < 0.01) BWG and ADG from d 22 to 28 for broilers fed the basal diet relative to other diets, but there was no difference for BWG and ADG across oil sources. However, broilers fed RBO had numerically greater BWD and ADG than those fed PO, likely because the RBO provided greater AME, AMEn, AME/GE, AMEn/GE (P < 0.01) as well as ether extract (EE) digestibility (P = 0.0536) relative to PO. The digestibility of palmitic (C16:0), stearic (C18:0), oleic (C18:1), and linoleic (C18:2) were greater (P < 0.01) in RBO than PO, which positively influenced the energy values for RBO. These results indicate RBO has greater ME and digestibility of EE and FA, which positively influenced the growth performance of AA broilers. Therefore, RBO can be used to replace PO in broiler diets.

Identification and management of GCK-MODY complicating pregnancy in Chinese patients with gestational diabetes.

Precise differentiation of glucokinase (GCK) monogenic diabetes from gestational diabetes mellitus (GDM) is critical for accurate management of the pregnancy outcome. We screened GCK-MODY complicating pregnancies in Chinese GDM patients, explored the pathogenesis of novel GCK mutations, and evaluated the patients' pregnancy outcome and management. The GCK gene from 411 GDM patients was screened with PCR-direct sequencing and multiplex ligation-dependent probe amplification (MLPA) and 15 GCK mutations were identified. We also retrospectively analyzed a total of 65 pregnancies from 21 GCK-MODY families, wherein 41 were from 15 maternal families and 24 were from six paternal families. Bioinformatic analysis and biochemical functional study were conducted to identify novel GCK mutations. In total, we identified 21 GCK mutations: 15 from the 411 GDM patients and six from 24 fathers. Of th Asp78Asn (GAC → AAC), Met87Arg (ATG → AGG), Leu451Val (CTT → GTT), Leu451Pro (CTG → CCG) and 1019 + 20G > A e mutations, five, i.e., were novel and deleterious, with markedly decreased enzyme activity and thermal stability. The unaffected offspring of GCK mutation-affected mothers were heavier than affected offspring (p < 0.001). Of 21 insulin-treated affected mothers, 10 had maternal hypoglycemia (47.6%) and seven had perinatal complications (33.3%), and the affected offspring of the insulin-treated affected mothers had significantly lower birth weights than that of the 20 diet-control affected mothers (p = 0.031). In this study, the prevalence of GCK-MODY complicating pregnancy in Chinese GDM patients was 3.6% (15/411). The defective GCK may contribute to the hyperglycemia in GCK-MODY. Insulin therapy is not beneficial for GCK-MODY complicating pregnancy and therefore should not be recommended.

Identification of Ala2Thr mutation in insulin gene from a Chinese MODY10 family.

More than 80% of maturity-onset diabetes of the young (MODY) in Chinese is genetically unexplained. To investigate whether the insulin gene (INS) mutation is responsible for some Chinese MODY, we screened INS mutations causing MODY10 in MODY pedigrees and explored the potential pathogenic mechanisms. INS mutations were screened in 56 MODY familial probands. Structure-function characterization and clinical profiling of identified INS mutations were conducted. An INS mutation, at the position 2 alanine-to-threonine substitution (A2T), was identified and co-segregated with hyperglycemia in a MODY pedigree. The A2T mutation converted an α-helix into a ß-sheet at the N-terminal of the signal peptide (SP) of preproinsulin. The A2T mutation did not affect preproinsulin translocation across endoplasmic reticulum (ER) membrane, but impaired its SP cleavage within the ER. In INS-1 cells transfected with an A2T mutant, glucose-stimulated insulin secretion (GSIS) was significantly decreased, while BiP luciferase activities were significantly increased compared to that of wild type (WT). We identified an INS-A2T mutation cosegregating with diabetes in a Chinese MODY pedigree. This mutation severely impaired SP cleavage and thus blocked the formation of proinsulin, resulting in enhanced ER stress, which may be responsible for decreased insulin secretion and subsequently, the onset of MODY10.

Ectopic TSH-secreting pituitary tumor: a case report and review of prior cases.

BACKGROUND: Ectopic TSH-secreting pituitary adenoma (TSH-oma) is a very unusual disorder. To date, there are only four cases reported. It is difficult to distinguish ectopic cases from both regular TSH-omas and resistance to thyroid hormone (RTH). CASE PRESENTATION: A newly identified case of ectopic TSH-oma arising from the nasal pharynx was described, and reports of four prior cases were reviewed. The patient was a 41-year-old male who developed what appeared to be typical hyperthyroidism and atrial fibrillation in 2009. Thyroid function tests showed elevated basal levels of free T3 (FT3, 24.08 pmol/L), free T4 (FT4, 75.73 pmol/L), and serum TSH (7.26 µIU/ml). Both TSH-oma and resistance to thyroid hormone syndrome were considered. TRH stimulating test was negative, whereas octreotide inhibition test showed a reduction in TSH by 30.8%. Furthermore, a large space-occupying lesion located at the nasopharynx was found by computed tomography and magnetic resonance imaging (MRI). A normal pituitary was visualized. Ectopic TSH-oma was preliminarily established. Using an endoscopic endonasal approach, the tumor was resected. Histological features and immunophenotypes were consistent with those of TSH-secreting tumor. The levels of both free thyroxine and TSH returned to normal ranges the day after surgery and remained within normal range for 48 months. CONCLUSIONS: Although exceedingly rare, ectopic TSH-oma should be considered for patients with inappropriate secretion of TSH with hyperthyroidism and pituitary tumor undetectable by computed tomography and MRI. To our knowledge, this is the first case followed up more than 4 years. The characteristics and successful interventions summarized in this report provide a guideline for clinicians.