Slow Weight Research Articles

Protective effects and mechanisms of HuDiChangRong capsule on TNBS-induced ulcerative colitis in mice

Ethnopharmacological relevanceUC, characterized by chronic inflammation primarily affecting the colon and rectum, follows a protracted relapsing course marked by inflammation and an abundance of free radicals at the onset. Hudichangrong Capsule (HDCRC), a traditional Chinese medicinal formula, has long been employed in the treatment of UC and chronic bacillary dysentery, exhibiting positive therapeutic outcomes and a high rate of cure in clinical practice. Aim of the studyThe precise mechanism underlying its efficacy for UC remains elusive. Our objective was to investigate the anti-inflammatory effect and underlying mechanisms of HDCRC on TNBS-induced UC. Materials and methodsHere, we introduced HDCRC and induced UC using TNBS. SPF BALB/c mice were divided into 6 groups as follows: control group, colitis model group, colitis treated with sulfasalazine (400 mg/kg) group, and colitis treated with HDCRC (156, 312, and 624 mg/kg) groups. To assess the effects of HDCRC on colitis, we measured body weight loss, disease activity index (DAI), colon length, tissue damage, degree of inflammation, immune capacity, and oxidative stress. Additionally, we evaluated the TLR-4/MyD88 pathway and its downstream signaling using immunohistochemistry, real-time qPCR, and Western blot. Network pharmacology was used for main target prediction. 16s rRNA was employed for gut microbiota detechtion and UPLC-QTOF-MS was used for its and its metabonomics. ResultsHDCRC significantly slowed weight loss, ameliorated DAI, restored colon length, alleviated TNBS-induced tissue damage. It exerted the therapeutic effects via reducing oxidative stress, restoring immune balance, normalizing the inflammatory mediator levels and restoring intestinal barrier integrity. Furthermore, HDCRC mainly alleviate UC via suppressing the TLR-4/MyD88 pathway and its downstream signaling. The key components of the downstream pathway, including TLR-4, MyD88, NF-κB p65, ERK, p-JNK, p38, p-JAK1, JAK1, p-STAT3, and STAT3, were improved, thereby ameliorating the TNBS-induced injury. In addition, HDCRC could regulate gut microbiota (eg. Erysipelaloclostridium,etc.) and its metabonomics (eg. Vitamin B6 metabolism) in UC mice. ConclusionsIn conclusion, HDCRC exerts a protective effect against TNBS-induced UC in mice by inhibiting the TLR-4/MyD88 pathway and its downstream signaling, and partially JAK1/STAT3, suppressing oxidative stress, regulating immunity, restoring intestinal barrier integrity, and regulating gut microbiota and its metabonomics.

Common Characteristics Between Frailty and Myotonic Dystrophy Type 1: A Narrative Review.

Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disorder often considered a model of accelerated aging due to the early appearance of certain age-related clinical manifestations and cellular and molecular aging markers. Frailty, a state of vulnerability related to aging, has been recently studied in neurological conditions but has received considerably less attention in neuromuscular disorders. This narrative review aims to describe 1) the common characteristics between Fried's frailty phenotype criteria (muscular weakness, slow gait speed, weight loss, exhaustion/fatigue, and low physical activity) and DM1, and 2) the psychological and social factors potentially contributing to frailty in DM1. This review gathered evidence suggesting that DM1 patients meet four of the five frailty phenotype criteria. Additionally, longitudinal studies report the deterioration of these criteria over time in DM1. Patients also exhibit psychological/cognitive and social factors that might contribute to frailty. Monitoring frailty criteria in the DM1 population could help to implement timely preventions and interventions to reduce the disease burden and severity of frailty symptoms.

Genomic and pathogenicity analysis of two novel highly pathogenic recombinant NADC30-like PRRSV strains in China, in 2023.

Porcine reproductive and respiratory syndrome viruses (PRRSVs) exhibit high mutability and recombination, posing challenges to their immunization and control. This study isolated two new PRRSV strains, GD-7 and GX-3, from samples collected in Guangdong and Guangxi in 2023. Whole-genome sequencing, along with phylogenetic and recombination analyses, confirmed that GD-7 and GX-3 are natural novel recombinant strains of NADC30 PRRSV. Moreover, we established a pathogenicity model for piglets and sows based on the two isolates. The results of piglet pathogenicity revealed that both GD-7 and GX-3 caused clinical symptoms such as fever, loss of appetite, depression, and slow weight gain. Moreover, we observed that the mortality rate of GD-7-inoculated group piglets was 33.3%, which was similar to that of piglets infected with other highly pathogenic PRRSV strains and exceeded the mortality rate of most NADC30-like PRRSV. In pregnant sow models, the survival rate of sows in the GD-7 group was 75%, in contrast to the GX-3 group, where no sow mortality was observed, and both strains resulted in abortion, mummified fetuses, and stillbirths. These results highlight the elevated pathogenicity of these recombinant strains in sows, with GD-7 mainly causing sows to abort, and GX-3 mainly causing sows to give birth to mummified fetuses. This study introduces two distinct clinical recombinant PRRSV strains that differ from the prevalent strains in China. This research furthers our understanding of the epidemiology of PRRSV and underscores the significance of ongoing monitoring and research in the face of evolving virus strains. Moreover, these discoveries act as early warnings, underscoring the necessity for active control and immunization against PRRSV.IMPORTANCESince the discovery of NADC30-like PRRSV in China in 2013, it has gradually become the dominant strain of PRRSV in China. NADC30-like PRRSV exhibits high recombination characteristics, constantly recombining with different strains, leading to the emergence of numerous novel strains. Of particular importance is the observation that NADC30-like PRRSV with different recombination patterns exhibits varying pathogenicity, which has a significant impact on the pig farming industry. This emphasizes the necessity of monitoring and responding to evolving PRRSV strains to develop effective immunization and control strategies. In this paper, we conducted pathogenicity studies on the isolated NADC30-like PRRSV and analyzed the differences in the genomes and pathogenicity of the different strains by recording clinical symptoms, temperature changes, detoxification tests, and changes in viremia and histopathology in infected pigs. This was done to provide a theoretical basis for the epidemiological situation and epidemic prevention and control of PRRSV.

Failure to Thrive, Metabolic Acidosis, and Diarrhea in a 7-Week-Old Infant.

A 7-week-old infant presented to the emergency department with fussiness, decreased oral intake, loose stool, and respiratory distress for 2 days. The patient was born full-term with an uncomplicated birth history but had a history of slow weight gain. He was alert, but toxic-appearing at presentation, hypothermic with signs of dehydration, and with respiratory failure. He was found to have severe anion gap metabolic acidosis, hypokalemia, elevated lactate, and hyperammonemia. He responded well to initial resuscitation and was admitted to the ICU for intravenous electrolyte replacement, bowel rest, and respiratory support. A workup was pursued for failure to thrive with severe malnutrition, hyperammonemia, hyperlactatemia, anemia, vitamin D deficiency, and electrolyte abnormalities. After stabilization, he was restarted on enteral feeds and had a recurrence of loose stool and severe electrolyte abnormalities, which were refractory to enteral supplementations and required readmission to the ICU. His hospital course extended several weeks, included several subspecialty consultations, and ended with a surprising diagnosis of exclusion based on his clinical response to therapy.

Evaluate the results of anesthesia and resuscitation of minimally invasive surgery for pediatric patients with ventricular septal defect at Cardiovascular Center, E hospital in 2022

Objective: Minimally invasive surgery has recently been implemented safely and effectively on children. The study aimed to evaluate the results of anesthesia and resuscitation in pediatric patients with ventricular septal defects (VSD) undergoing minimally invasive surgery. Methods: A cross-sectional study from January 1, 2021 to June 30, 2022 on 65 patients underwent minimally invasive surgery to repair ventricular septal defect, at Cardiovascular Center, E Hospital. Result: A toltal of 65 children aged from 1 month to 34 months, mean weight of 9.0 ± 6.3kg, mean height of 73.6 ± 22.1cm, with main clinical symptoms of slow weight gain (62.5%) and grade I heart failure (87.7%). The most common VSD location was perimembranous VSD (67.7%) with an mean size of 5.7±2.6 mm. The mean surgical time was 175 minutes with cardiopulmonary bypass time and aortic cross-clamp time of 77.5 and 53.0 minutes, respectively. Postoperative hemodynamic parameters changed statistically significantly compared to pre-operation: blood pressure decreased, heart rate increased, lactate level increased, P/F ratio decreased, blood potassium level decreased. The patient mainly needed to use 1 vasopressor, 1 type of sedative analgesic, continuous diuresis, and prophylactic antibiotics with a vasopressor withdrawal time of 34.2 hours, a sedation withdrawal time of 13.35 hours, and a sedative withdrawal time of 13.35 hours. Intubation time of 20.8 hours (minimum 2 hours) and length of stay ICU was 3.8 days. Postoperative complications were low, mainly pneumonia (9.2%) and residual shunt (9.2%), and no death was observed. Conclusion: Minimally invasive ventricular septal defect surgery showed that the anesthesia and surgical process did not change much, with relatively fast post-operative recovery results, short medication time, quick recovery, and no recording severe complications.

Physical frailty, genetic predisposition, and incident arrhythmias.

Cross-sectional evidence suggests a possible link between frailty and atrial fibrillation (AF). It remains unclear whether frailty and incident arrhythmias are longitudinally associated. This study aimed to determine whether the frailty phenotype is longitudinally associated with incident arrhythmias, especially AF. In this prospective cohort of UK Biobank, individuals with arrhythmias at baseline, those without data for frailty phenotype, and no genetic data were excluded. Five domains of physical frailty, including weight loss, exhaustion, low physical activity, low grip strength, and slow gait speed, were assessed. A total of 142 single-nucleotide polymorphisms was used to calculate the polygenic risk score (PRS) for AF. Hospital inpatient records and death records were used to identify incident arrhythmias. This study included 464154 middle-aged and older adults (mean age 56.4±8.1years, 54.7% female) without arrhythmia at baseline. During a median follow-up of 13.4years (over 5.9 million person-years), 46454 new-onset arrhythmias cases were recorded. In comparison with non-frailty, the multivariable-adjusted hazard ratios (HRs) of AF were 1.12 (95% CI: 1.09, 1.15, P<0.0001) and 1.44 (95% CI: 1.36, 1.51, P<0.0001) for participants with pre-frailty and frailty, respectively. Similar associations were observed for other arrhythmias. We found that slow gait speed presented the strongest risk factor in predicting all arrhythmias, including AF (HR 1.34, 95% CI: 1.30, 1.39), bradyarrhythmias (HR 1.30, 95% CI: 1.22, 1.37), conduction system diseases (HR 1.29, 95% CI: 1.22, 1.36), supraventricular arrhythmias (HR 1.32, 95% CI: 1.19, 1.47), and ventricular arrhythmias (HR 1.37, 95% CI: 1.25, 1.51), with all P values <0.0001. In addition to slow gait speed, weight loss (HR 1.13, 95% CI: 1.09, 1.16, P<0.0001) and exhaustion (HR 1.11, 95% CI: 1.07, 1.14, P<0.0001) were significantly associated with incident AF, whereas insignificant associations were observed for physical activity (HR 1.03, 95% CI: 0.996, 1.08, P=0.099) and low grip strength (HR 1.00, 95% CI: 0.97, 1.03, P=0.89). We observed a significant interaction between genetic predisposition and frailty on incident AF (P for interaction <0.0001), where those with frailty and the highest tertile of PRS had the highest risk of AF (HR 3.34, 95% CI: 3.08, 3.61, P<0.0001) compared with those with non-frailty and the lowest tertile of PRS. Physical pre-frailty and frailty were significantly and independently associated with incident arrhythmias. Although direct causal inference still needs to be further validated, these results suggested the importance of assessing and managing frailty for arrhythmia prevention.

Outcomes of Percutaneous Endoscopic Gastrostomy in Huntington's Disease at a Tertiary Center.

Clinically assisted nutrition and hydration via percutaneous endoscopic gastrostomy (PEG) is a therapeutic option to ameliorate the difficulties associated with enhanced catabolism, weight loss, and dysphagia in Huntington's disease (HD). The objective is to provide insights into demographics, staging (Shoulson-Fahn), complications, weight trajectories, and survival rates in people with HD (pwHD) who underwent PEG. This retrospective study included 705 consecutive pwHD who attended our HD clinic between July 2006 and March 2024, of whom 52 underwent PEG. A control group (n = 52), comprising pwHD without PEG, were closely matched for sex, stage, age, CAG length, and disease burden score at PEG. The study was registered as a service evaluation at the National Hospital for Neurology and Neurosurgery. PEG prevalence was 15.0% (n = 52/347) among manifest pwHD: 4.8% (n = 3/62) for Stage 3; 33.3% (n = 16/48) for stage 4; and 44.1% (n = 30/68) for stage 5. Commonest indications were dysphagia, weight loss, and inadequate oral intake. Complications included chest infection, tube dislodgement, and peristomal and skin infections. Modeling of weight trajectories after PEG found no difference between PEG and non-PEG groups. Mortality rate was 34.6% (n = 18/52) in the PEG and 36.5% (n = 19/52) in the non-PEG groups (P = 0.84). Treatment duration (until study endpoint or death) was 3.48 years (interquartile range = 1.71-6.02; range = 0.23-18.8), with 65.4% (n = 34/52) alive at the study endpoint. PEG in pwHD at-risk for weight loss may help slow weight loss. Prospective studies are required to strengthen PEG decision-making in pwHD. PEG survival was much longer than other dementias, highlighting the need to consider PEG independently in pwHD.

Lacticaseibacillus rhamnosus Strains for Alleviation of Irritable Bowel Disease and Chronic Fatigue Syndrome.

Lacticaseibacillus rhamnosus is applied as a probiotic to alleviate various metabolic, gastrointestinal, and psychological symptoms and diseases, and its probiotic effectiveness is strain-specific. In this study, we obtained 21 strains of Ls. rhamnosus, and their genomes were sequenced. We defined the pan- and core-genomes of Ls. rhamnosus. Phenotypes such as the assimilation of carbohydrates and antibiotic resistance were experimentally characterized and associated with genome annotations. Nine strains were selected and tested for growth rates, tolerance to acidity/alkalinity and bile acids, the production of short-chain fatty acids, and competition with pathogenic microbes. Strains WL11 and WL17 were targeted as potential probiotics and were applied in mouse model tests for the alleviation of chronic fatigue syndrome (CFS) and irritable bowel syndrome (IBS). The results showed that WL11 and WL17 effectively alleviated slow body weight gain, anxiety, poor memory, and cognitive impairment in CFS mouse models. They also reduced the expression of pro-inflammatory factors, such as TNF-α and IL-6, and alleviated intestinal peristalsis, visceral hypersensitivity, and anxiety-like behavior in IBS mouse models. This study reports new Ls. rhamnosus strain resources and their effect on alleviation of both IBS and CFS symptoms with mouse models; the probiotic functions of those strains in human patients remain to be further tested.

Effects of rapid or slow body weight reduction on glucose tolerance during equivalent weight loss in rats fed high-fat diet

Effects of rapid or slow body weight reduction on glucose tolerance during equivalent weight loss in rats fed high-fat diet

Anti-obesity effects of potential probiotic Lactobacillus strains isolated from Mongolian fermented dairy products in high-fat diet-induced obese rodent model.

This study aims to investigate the anti-obesity properties of lactic acid bacteria (LAB) isolated from fermented dairy products such as "Airag" and "Khoormog" in Mongolia. These traditional dairy products are widely used in Mongolia and believe in having potential probiotic, anti-diabetes, anti-cancer, and anti-tuberculosis properties and are made from unheated two-humped camel milk and mare milk, respectively. We chose three LAB strains based on their probiotic characteristics, including tolerance of gastric and bile acids. Then we checked the anti-obesity activity of probiotic strains in vivo. An animal model was evaluated in twenty male C57BL/6J mice by inducing obesity with a high-fat diet (HFD), which was divided into five groups: regular diet group (Negative control), HFD group (Positive control), HFD with Lacticaseibacillus paracasei X-1 (X-1), Lacticaseibacillus paracasei X-17 (X-17), and Limosilactobacillus fermentum BM-325 (BM-325). For six weeks, 5 × 109 colony-forming units (CFU) of bacteria were given orally to the LAB-fed groups. Fasting blood glucose (FBG), lipid profiles, organ index, and organ morphology were all measured. The probiotic strains suppressed growth in adipose cell volume, stabilized FBG, reduced liver cell degeneration, and slowed HFD-induced body weight gain. The results suggest that some strains increase general metabolism while lowering body weight.

Effects of electroacupuncture with "intestinal disease prescription" on NLRP3 inflammasome and intestinal mucosal barrier in rats with acute ulcerative colitis.

To observe the effects of electroacupuncture (EA) with "intestinal disease prescription" on the intestinal mucosal barrier and NLRP3 inflammasome in rats with dextran sulfate sodium (DSS)-induced acute ulcerative colitis (UC), and explore the underlying mechanism of EA with "intestinal disease prescription" for the treatment of UC. Thirty-two healthy male SPF-grade SD rats were randomly divided into a blank group, a model group, a medication group, and an EA group, with 8 rats in each group. Except for the blank group, the UC model was established by administering 5% DSS solution for 7 days. After modeling, the rats in the medication group were treated with mesalazine suspension (200 mg/kg) by gavage, while the rats in the EA group were treated with acupuncture at bilateral "Tianshu" (ST 25), "Shangjuxu" (ST 37) and "Zhongwan" (CV 12), with the ipsilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37) connected to the electrodes of the EA instrument, using disperse-dense wave, with a frequency of 10 Hz/50 Hz, and each intervention lasted for 20 minutes. Both interventions were performed once daily for 3 days. The general conditions of rats were observed daily. After intervention, the disease activity index (DAI) score was calculated; colon tissue morphology was observed using HE staining; serum levels of pro-inflammatory cytokines (interleukin [IL]-18, IL-1β) were measured by ELISA; protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in colon tissues was detected by Western blot; positive expression of zonula occludens-1 (ZO-1) and Occludin in colon tissues was examined by immunofluorescence. Compared with the blank group, the rats in the model group exhibited poor general conditions, slow body weight gain, shortened colon length (P<0.01), increased DAI score and spleen index (P<0.01), elevated serum IL-18 and IL-1β levels, and increased protein expression of NLRP3, ASC, and Caspase-1 in colon tissues (P<0.01), along with decreased positive expression of ZO-1 and Occludin in colon tissues (P<0.01). Compared with the model group, the rats in the medication group and the EA group exhibited improved general conditions, accelerated body weight gain, increased colon length (P<0.05), reduced DAI scores and spleen indexes (P<0.05), decreased serum IL-18 and IL-1β levels, and lower protein expression of NLRP3, ASC and Caspase-1 in colon tissues (P<0.05), as well as increased positive expression of ZO-1 and Occludin in colon tissues (P<0.05). There were no significant differences in the above indexes between the medication group and the EA group (P>0.05). Compared with the blank group, the rats in the model group exhibited disrupted colon mucosal morphology, disordered gland arrangement, and atrophy of crypts, along with significant inflammatory cell infiltration. Compared with the model group, the rats in both the medication group and the EA group showed relatively intact colon mucosal morphology, with restored and improved gland and crypt structures, and reduced inflammatory cell infiltration. EA with "intestinal disease prescription" has a significant therapeutic effect on DSS-induced UC, possibly by regulating the expression of NLRP3 inflammasome and proteins related to the intestinal mucosal barrier, thereby alleviating symptoms of ulcerative colitis.

The Inhibitory Effect of Early Pregnancy Factor on Red Meat Neu5Gc-Mediated Antibody Production in CMAH-/- Mice.

The meat derived from mammals such as cows, sheep, and pigs is commonly referred to as red meat. Recent studies have shown that consuming red meat can activate the immune system, produce antibodies, and subsequently develop into tumors and cancer. This is due to the presence of a potential carcinogenic compound in red meat called N-ethanol neuraminic acid (Neu5Gc). Neu5Gc is a common sialic monosaccharide in mammals, synthesized from N-acetylneuraminic acid (Neu5Ac) in the body and typically present in most mammals. However, due to the lack of the CMAH gene encoding the cytidine 5'-monophosphate Neu5Ac hydroxylase, humans are unable to synthesize Neu5Gc. Compared to primates such as mice or chimpanzees, the specific loss of Neu5Gc expression in humans is attributed to fixed genome mutations in CMAH. Although Neu5Gc cannot be produced, it can be introduced from specific dietary sources such as red meat and milk, so it is necessary to use mice or chimpanzees that knock out the CMAH gene instead of humans as experimental models. Further research has shown that early pregnancy factor (EPF) has the ability to regulate CD4+T cell-dependent immune responses. In this study, we established a simulated human animal model using C57/BL6 mice with CMAH gene knockout and analyzed the inhibitory effect of EPF on red meat Neu5Gc-induced CMAH-/- C57/BL6 mouse antibody production and chronic inflammation development. The results showed that the intervention of EPF reduced slow weight gain and shortened colon length in mice. In addition, EPF treatment significantly reduced the levels of anti Neu5Gc antibodies in the body, as well as the inflammatory factors IL-6 and IL-1β, TNF-α and the activity of MPO. In addition, it also alleviated damage to liver and intestinal tissues and reduced the content of CD4 cells and the expression of B cell activation molecules CD80 and CD86 in mice. In summary, EPF effectively inhibited Neu5Gc-induced antibody production, reduced inflammation levels in mice, and alleviated Neu5Gc-induced inflammation. This will provide a new re-search concept and potential approach for developing immunosuppressants to address safety issues related to long-term consumption of red meat.

Epidemiological investigation of coccidiosis and associated risk factors in broiler chickens immunized with live anticoccidial vaccines in China.

Coccidiosis is a costly intestinal disease of chickens caused by Eimeria species. This infection is associated with high mortality, reduced feed efficiency, and slowed body weight gain. The diagnosis and control of coccidiosis becomes challenging due to the fact that chickens can be infected by seven different Eimeria species and often occur mixed-species co-infections. Grasping the epidemiology of Eimeria species is crucial to estimate the efficiency of poultry management. This study aimed to explore the distribution of Eimeria species in broiler chickens in China after administering live anticoccidial vaccines. A total of 634 samples were obtained, and the survey results showed that the prevalence of Eimeria was 86.12% (546/634), and the most common species were E. acervulina (65.62%), E. necatrix (50.95%), E. mitis (50.79%), E. tenella (48.42%), and E. praecox (41.80%). Most samples indicated mixed-species infections (an average of 3.29 species per positive sample). Notably, 63.98% of samples contain 3 to 5 Eimeria species within a single fecal sample. The most prevalent combinations were E. acervulina-E. tenella (38.96%) and E. acervulina-E. necatrix (37.22%). Statistical analysis showed that flocks vaccinated with trivalent vaccines were significantly positive for E. necatrix in grower chickens (OR = 3.30, p < 0.05) compared with starter chickens, and tetravalent vaccinated flocks showed that starter chickens demonstrated a higher susceptibility to E. tenella-E. brunetti (OR = 2.03, p < 0.05) and E. acervulina-E. maxima (OR = 2.05, p < 0.05) compared with adult chickens. Geographically, in the case of tetravalent vaccine-immunized flocks, a substantial positive association was observed between E. necatrix infection rates and flocks from eastern (OR = 3.88, p < 0.001), central (OR = 2.65, p = 0.001), and southern China (OR = 3.17, p < 0.001) compared with southwestern China. This study also found a positive association between E. necatrix (OR = 1.64, p < 0.05), E. acervulina (OR = 1.59, p < 0.05), and E. praecox (OR = 1.81, p < 0.05) infection and coccidiosis occurrence compared with non-infected flocks in tetravalent vaccinated flocks. This molecular epidemiological investigation showed a high prevalence of Eimeria species in the field. The emergent species, E. brunetti and E. praecox, might be incorporated into the widely-used live vaccines in the future. These insights could be useful in refining coccidiosis control strategies in the poultry industry.

Altered metabolome and microbiome associated with compromised intestinal barrier induced hepatic lipid metabolic disorder in mice after subacute and subchronic ozone exposure

Exposure to ozone has been associated with metabolic disorders in humans, but the underlying mechanism remains unclear. In this study, the role of the gut-liver axis and the potential mechanism behind the metabolic disorder were investigated by histological examination, microbiome and metabolome approaches in mice during the subacute (4-week) and subchronic (12-week) exposure to 0.5 ppm and 2.5 ppm ozone. Ozone exposure resulted in slowed weight gain and reduced hepatic lipid contents in a dose-dependent manner. After exposure to ozone, the number of intestinal goblet cells decreased, while the number of tuft cells increased. Tight junction protein zonula occludens-1 (ZO-1) was significantly downregulated, and the apoptosis of epithelial cells increased with compensatory proliferation, indicating a compromised chemical and physical layer of the intestinal barrier. The hepatic and cecal metabolic profiles were altered, primarily related to lipid metabolism and oxidative stress. The abundance of Muribaculaceae increased dose-dependently in both colon and cecum, and was associated with the decrease of metabolites such as bile acids, betaine, and L-carnitine, which subsequently disrupted the intestinal barrier and lipid metabolism. Overall, this study found that subacute and subchronic exposure to ozone induced metabolic disorder via disturbing the gut-liver axis, especially the intestinal barrier. These findings provide new mechanistic understanding of the health risks associated with environmental ozone exposure and other oxidative stressors.

Transcriptome Analysis of the Preservation Effect of Three Essential Oil Microcapsules on Okra

Cinnamon (Cinnamomum sp.) essential oil microcapsules, oregano (Origanum sp.) essential oil microcapsules, and oregano–thyme (Thymus sp.) essential oil microcapsules are rarely used in the postharvest preservation treatment of okra (Abelmoschus esculentus L.). The mechanism of these three essential oil microcapsules on the postharvest preservation of okra is also not yet well understood. In this study, fresh okra was preserved by three kinds of essential oil microcapsules (cinnamon essential oil microcapsules, oregano essential oil microcapsules, and oregano–thyme essential oil microcapsules). The effect of essential oil microcapsules on the postharvest storage quality of okra was discussed. We also used RNA-Seq to preliminarily explore the mechanism of oregano–thyme essential oil microcapsules on the pre-harvest storage quality of okra. The results showed that the three kinds of essential oil microcapsules could maintain the high sensory evaluation quality and firmness of okra, slow down the increase in respiratory intensity, slow down the total number of colonies on the fruit surface, and slow down weight loss. Through analysis, it was found that the effect of oregano–thyme essential oil microcapsules was remarkably better than that of cinnamon essential oil microcapsules and oregano essential oil microcapsules. The preservation mechanism of oregano–thyme essential oil microcapsules on postharvest okra was preliminarily elucidated by RNA-Seq. This study provides a certain basis for a follow-up study of essential oil microcapsules in the preservation of okra.

High-Reliability and Self-Rectifying Alkali Ion Memristor through Bottom Electrode Design and Dopant Incorporation.

Ionic memristor devices are crucial for efficient artificial neural network computations in neuromorphic hardware. They excel in multi-bit implementation but face challenges like device reliability and sneak currents in crossbar array architecture (CAA). Interface-type ionic memristors offer low variation, self-rectification, and no forming process, making them suitable for CAA. However, they suffer from slow weight updates and poor retention and endurance. To address these issues, the study demonstrated an alkali ion self-rectifying memristor with an alkali metal reservoir formed by a bottom electrode design. By adopting Li metal as the adhesion layer of the bottom electrode, an alkali ion reservoir was formed at the bottom of the memristor layer by diffusion occurring during the atomic layer deposition process for the Na:TiO2 memristor layer. In addition, Al dopant was used to improve the retention characteristics by suppressing the diffusion of alkali cations. In the memristor device with optimized Al doping, retention characteristics of more than 20 h at 125 °C, endurance characteristics of more than 5.5 × 105, and high linearity/symmetry of weight update characteristics were achieved. In reliability tests on 100 randomly selected devices from a 32 × 32 CAA device, device-to-device and cycle-to-cycle variations showed low variation values within 81% and 8%, respectively.

Nutritional and exercise interventions to improve conception in women suffering from obesity and distinct nosological entities.

Infertility among women, particularly those living with obesity, presents a multifaceted challenge with implications for reproductive health worldwide. Lifestyle interventions, mainly focusing on weight loss, have emerged as promising strategies to improve fertility outcomes in this population. This review aims to explore the effectiveness of various lifestyle interventions, encompassing dietary modifications and exercise regimens, in enhancing fertility outcomes among women with obesity and associated conditions such as polycystic ovary syndrome, congenital adrenal hyperplasia, type 2 diabetes mellitus, premenopause, hypothyroidism and eating disorders. Methodology of study search encompass a broad spectrum, ranging from interventions targeting weight management through slow or rapid weight loss to dietary approaches emphasizing whole food groups, specific nutrients, and dietary patterns like low-carbohydrate or ketogenic diets, as well as the Mediterranean diet. By synthesizing existing findings and recommendations, this review contributes to the understanding of lifestyle interventions in addressing infertility, with an emphasis on the population of women of reproductive age with excess weight and known or unknown infertility issues, while promoting their integration into clinical practice to optimize reproductive health and overall well-being.

The ameliorative mechanism of Lactiplantibacillus plantarum NJAU-01 against D-galactose induced oxidative stress: a hepatic proteomics and gut microbiota analysis.

Probiotic intervention is an effective strategy to alleviate oxidative stress-related diseases. Our previous studies found that Lactiplantibacillus plantarum NJAU-01 (NJAU-01) exhibited antioxidant effects in a D-galactose (D-gal)-induced aging mouse model. However, the underlying mechanism remains to be unveiled. This study was aimed to investigate the ameliorative effect and mechanism of NJAU-01 against oxidative stress induced by D-gal. The results showed that NJAU-01 could reverse the tendency of a slow body weight gain induced by D-gal. NJAU-01 relieved hepatic oxidative stress via increasing the hepatic total antioxidant capacity and antioxidant enzyme activities including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). Moreover, the malondialdehyde (MDA) level was reversed after NJAU-01 supplementation. The proteomic results showed that there were 201 differentially expressed proteins (DEPs) between NJAU-01 and D-gal groups. NJAU-01 regulated the expressions of glutathione S-transferase Mu 5 (Gstm5), glutathione S-transferase P2 (Gstp2) and NADH dehydrogenase 1α subcomplex subunit 7 (Ndufa7) related to oxidative stress, and autophagy protein 5 (Atg5) and plasma alpha-L-fucosidase (Fuca2) involved in autophagy, etc. 16S rDNA sequencing results showed that NJAU-01 supplementation could regulate the gut microbiota dysbiosis induced by D-gal via increasing the relative abundances of the phylum Firmicutes and the genus Lactobacillus and reducing the relative abundances of the phylum Bacteroidetes and the genera Lachnospiraceae_NK4A136_group as well as Prevotellaceae_UCG-001, etc.. Spearman correlation analysis results showed that the altered gut microbiota composition had a significant correlation with antioxidant enzyme activities and the DEPs related to oxidative stress. Overall, NJAU-01 alleviated hepatic oxidative stress induced by D-gal via manipulating the gut microbiota composition and hepatic protein expression profile.

Ghrelin Alleviates Inflammation, Insulin Resistance, and Reproductive Abnormalities in Mice with Polycystic Ovary Syndrome via the TLR4-NF-κB Signaling Pathway.

Polycystic ovary syndrome (PCOS) commonly impacts fertile females with potentially severe effects on fertility and metabolism. Blood ghrelin levels are lower in PCOS patients, and exogenous supplements have been proposed for their potential to trigger anti-inflammatory effects at the cellular level. This study aimed to investigate whether pretreatment with ghrelin reduced inflammation, insulin resistance, and reproductive abnormalities in PCOS and the underlying mechanism of this disorder. Ghrelin supplementation was first tested in an inflammation model using human ovarian granulosa cells (KGN cells) that were built by treated with Lipolyaccharide. KGN cells were pretreated with ghrelin and exposed to lipopolysaccharide (LPS). Inflammatory gene expression and cytokine production were analyzed by Enzyme-linked immunosorbent assay (ELISA). Based on these results, the PCOS mice model was built with Dehydroepiandrosterone (DHEA) and a high-fat diet. The mRNA and protein expressions of inflammatory factors including Toll-like receptor 4 (TLR4), nuclear factor kappa-B-p65 (NF-κB-p65), Phospho-NF-κB-p65 (p-NF-κB-p65) and myeloid differentiation factor 88 (MYD88) related to the TLR4/NF-κB signaling pathway were evaluated in KGN cells and mouse ovarian tissues using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) and western blot, respectively. Lipid metabolism was quantified via an automated biochemical analyzer. The mRNA and protein expressions of interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) in ghrelin pretreated KGN cells were lower than the LPS group (p < 0.05). Protein expression was reduced for TLR4, NF-κB-p65, and MYD88 within KGN cells of ghrelin groups compared to the LPS group (p < 0.05). Ghrelin treatment restored the estrous cycle and slowed weight gain and abdominal fat weight of PCOS mice (p < 0.05). Ghrelin treatment decreased the serum concentrations of testosterone, luteinizing hormone, insulin, IL-6, IL-1β, and TNF-α compared to the PCOS group (p < 0.05). Estradiol concentrations of mice treated with ghrelin were higher than the PCOS group (p < 0.05). The concentrations of low and high-density lipoprotein, triglyceride, and cholesterol in mice treated with ghrelin were lower than in the PCOS mice (p < 0.05). Inflammatory gene expression for IL-6, IL-1β, TNF-α, TLR4, NF-κB-p65, and MYD88 decreased in the ovarian tissues of ghrelin-treated mice compared to the PCOS group (p < 0.05), along with reduced protein expression of TLR4, p-NF-κB-p65, and MYD88 (p < 0.05). In the present study, ghrelin treatment effectively reduced inflammation in vitro, and attenuated insulin resistance and reproductive abnormalities in PCOS mice through the TLR4/NF-κB signaling pathway, highlighting potential therapeutic avenues for future PCOS treatments and research directions.

THE PATTERN OF SILVER-RUSSELL SYNDROME: OWN OBSERVATION

Silver-Russell syndrome (SRS) –is an orphan disease characterized by intrauterine and postnatal growth retardation. Children have special phenotypes, difficulties in feeding, the threat of insulin resistance, hypoglycemia, and accelerated sexual development. Aim: Increasing the effectiveness of SRS diagnosis based on the study of the features of the clinical and genetic course. Material and Methods: Clinical examination, blood tests, biochemistry, genetic tests, polymer chain reactions, and ultrasound examination have been carried out. Results: The child, 5 years old, was born from 2nd full-term pregnancy at 37 weeks, 2nd cesarean delivery with a body weight of 1900 g, height of 46 cm, head circumference of 30 cm, and chest circumference of 27 cm. Apgar scored 6/7 points. Neonatal adaptation disorders, intrauterine development, symmetrical shape, risk of hemolytic disease of the newborn according to the Rhesus factor (total bilirubin 190.0 μmol/l). The child had a special phenotype: asymmetry of the body with a relative increase in head circumference, a small triangular face with a protruding forehead, a narrow chin, a small jaw, and curvature of the 5th finger. From birth, insufficient body weight gain was observed (60 g per week, 400 g from birth in 6 weeks), which was explained by physiological vomiting and lactase deficiency (homozygous carrier of genotype C/C during PCR analysis). Body weight at the age of 1 year 5.200 g, height 63 cm, at the age of 5 years body weight 10.2 kg, height 91 cm. The child had heightened intellectual and psychological development. For the sake of differential diagnosis, a study was conducted for the presence of Gaucher’s disease (the result was negative). The results of immunologic tests: IgA 0.77 g/l, tTgIgA&lt; 2.0 units/ml, and tTgIgG 0.05 denied the presence of celiac disease. Clinical diagnosis was established according to the Netchine-Harbison scoring system (NH-CSS), which consists of 6 clinical criteria of NH-CSS. Gene sequencing revealed changes in the variant of uncertain significance SLK25A15, the genetic significance of which is unknown, which did not allow to confirm the diagnosis. Invitae Chromoso-mal Microarray Analysis of genome research on microdeletions (duplications) revealed, with a normal female genomic profile, uniparental dysfunction with two areas of homozygosity ROH&gt;5Mb (GRCh370) in chromosome 20: 20q13-p12.3(1-6690101; 6.69Mb and 20q13.32- q13.33(57394420- 63025520); 5.63 Mb. This change is characterized as a SRS variant, which created the basis for the diagnosis. Therefore, the child has a genetically confirmed diagnosis of SRS and congenital lactose intolerance. Somatotropic hormone (Omnitrop) was prescribed at a dose of 0.6 mg/day continuously. Conclusions: 1. The child’s SRS diagnosis was established on the basis of phenotype data, slow weight gain and growth, genetic research data, and the exclusion of the possibility of other conditions with the impaired physical development of the child. 2. The child needs a multidisciplinary approach to observation and treatment by a pediatrician or family doctor, endocrinologist, geneticist, nutritionist, surgeon, and gynecologist.