Body Weight Loss Research Articles

Fu-Zheng-Li-Fei Recipe (FZLFR) in the treatment of cancer cachexia: Exploration of the efficacy and molecular mechanism based on chemical characterization, experimental research and network pharmacology

Ethnopharmacological relevanceFZLFR was derived from a classic traditional Chinese medicine recipe, the Shiquan-Dabu decoction. FZLFR is commonly used in clinical practice to address muscle loss and associated cancer cachexia. However, the mechanism of by which FZLFR acts in cancer cachexia remains unclear. AimThis study aimed to assess the effects and explore the potential mechanism of action of FZLFR in treating cancer cachexia. MethodsCancer cachexia was induced by inoculating Lewis lung carcinoma cells into the right flank of male C57BL/6 mice. The efficacy of FZLFR was evaluated by comparing changes in body weight, tumor mass, food intake, survival time, weight, and cross-sectional area of the gastrocnemius and anterior tibial muscles. Moreover, inflammatory cytokines, such as TNF-α and IL-6, were detected by ELISA. The chemical components of FZLFR were analyzed using ultra-performance liquid chromatography-coupled with time-of-flight mass spectrometry. Network pharmacology analysis was performed to screen the core targets and potential pathways involved in FZLFR treatment of cancer cachexia. Molecular docking was used to analyze the binding ability of the core targets and key compounds. The expression levels of core targets and targets correlated with skeletal muscle atrophy were also assessed using western blotting. ResultsFZLFR enhanced the food intake and survival rate of mice with cancer cachexia. It also alleviated tumor-induced body weight loss, tumor growth, and muscle fiber atrophy in these mice. Additionally, it improved the weight and cross-sectional area of the gastrocnemius and anterior tibial muscles. FZLFR down-regulated the serum levels of TNF-α and IL-6. UPLC-ESI-Q-TOF-MS analysis identified 184 compounds in FZLFR. Network pharmacology analysis predicted that TNF signaling pathway, ErbB signaling pathway and VEGF signaling pathway might be essential in FZLFR action. Molecular docking showed that kaempferol, upafolin, apigenin, and luteolin might play key roles in FZLFR treatment. Moreover, FZLFR decreased MAFBx1, MURF1, NF-κB, TWEAK, MAPK8, and EGFR expression levels. FZLFR enhanced the expression of VEGFA and ESR1, as demonstrated by western blotting. ConclusionsFZLFR increased food intake and alleviated muscle atrophy in mice with cancer cachexia. The potential pharmacological mechanisms underlying its anticachexia effects include reducing inflammation, enhancing muscle vascular growth, inhibiting tumor angiogenesis, and modulating estrogen receptors.

Zinc pyrithione ameliorates colitis in mice by interacting on intestinal epithelial TRPA1 and TRPV4 channels

AimsAlthough zinc pyrithione (ZPT) has been studied as topical antimicrobial and cosmetic consumer products, little is known about its pharmacological actions in gastrointestinal (GI) health and inflammation. Our aims were to investigate the effects of ZPT on transient receptor potential (TRP) channels and Ca2+ signaling in intestinal epithelial cells (IECs) and its therapeutic potential for colitis. Main methodsDigital Ca2+ imaging and patch-clamp electrophysiology were performed on human colonic epithelial cells (HCoEpiC) and rat small intestinal epithelial cells (IEC-6). The transcription levels of proinflammatory cytokines such as IL-1β were detected by RTq-PCR. Dextran sulfate sodium (DSS) was used to induce colitis in mice. Key findingsZPT dose-dependently induced Ca2+ signaling and membrane currents in IECs, which were attenuated by selective blockers of transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 4 (TRPV4) channels, respectively. Interestingly, Ca2+ entry via TRPA1 channels inhibited the activity of TRPV4 channels in HCoEpiC, but not vice versa. ZPT significantly promoted migration of IECs by activating TRPA1 and TRPV4 channels. ZPT reversed lipopolysaccharides (LPS)-induced changes in mRNA expression of TRPA1 and TRPV4. Moreover, ZPT decreased mRNA levels of pro-inflammatory factors promoted by LPS in HCoEpiC, which were restored by selective TRPA1 blocker. In whole animal studies in vivo, ZPT significantly ameliorated DSS-induced body weight loss, colon shortening and increases in stool score, serum calprotectin and lactic acid (LD) in mouse model of colitis. SignificanceZPT exerts anti-colitic action likely by anti-inflammation and pro-mucosal healing through TRP channels in IECs. The present study not only expands pharmacology spectrum of ZPT in GI tract, but also repurposes it to a potential drug for colitis therapy.

Comparison of the influence of postoperative oral nutritional supplementation between octogenarian and non-octogenarian patients undergoing gastrectomy for cancer.

Despite recent reports, the effectiveness of postoperative oral nutritional supplementation (ONS) on body weight loss and malnutrition after gastrectomy remains controversial. We aimed to elucidate the effectiveness of ONS especially in octogenarian patients undergoing oncological gastrectomy. A total of 286 consecutive patients who underwent gastrectomy for gastric cancer were eligible. Postoperative body weight loss, malnutrition, and sarcopenia were compared between patients with and without postoperative ONS among octogenarian patients aged ≥ 80 years and non-octogenarian patients aged < 80 years. In this study, 36 (62.1%) octogenarian and 121 (53.1%) non-octogenarian patients continued postoperative ONS for three months. The clinicopathologic characteristics were not different between the ONS (-) and ONS (+) groups among the octogenarian and non-octogenarian patients. The changes in body weight and serum albumin levels at postoperative 1 year were different between the ONS (-) and ONS (+) groups (P = 0.03 and P = 0.04, respectively) among the octogenarian patients, but not between the two groups among the non-octogenarian patients (P = 0.99 and P = 0.29, respectively). Also, the decline in psoas muscle mass index at postoperative 6 months and 1 year was significantly lower in the ONS (+) group than in the ONS (-) group (P < 0.01 and P < 0.01, respectively). In addition, similar results were found in octogenarian patients who underwent distal gastrectomy. Postoperative ONS could prevent body weight loss, malnutrition, and sarcopenia especially in octogenarian patients who underwent gastrectomy for gastric cancer.

Evaluation of alpha Klotho and fibroblast growth factor-23 levels in Iraqi patients with Graves’ disease

Background &amp; Objective: Graves’ disease (GD) is an autoimmune condition that targets the thyroid gland, resulting in excessive stimulation and synthesis of thyroid hormones. Excessive synthesis of these hormones can lead to symptoms such as loss of body weight, accelerated heart rate, irritability, reduced tolerance to heat, and excessive perspiration. Alpha-Klotho (KL), a protein crucial for physiological processes, is also involved in GD. The defective immunological condition of GD patients may increase Klotho expression, and the enhanced expression of fibroblast growth factor-23 (FGF23) in GD may be linked to the disease pathophysiology. We investigated serum levels of KL and FGF23 in Iraqi patients with Graves’ disease, analyzing correlations with clinical status and evaluating their potential as biomarkers for disease activity. Methodology: We conducted this cross-sectional study at The National Diabetes Center, Mustansiriyah University, between December 2022 and April 2023. The study involved 103 patients diagnosed with GD, and 103 patients, aged 21-70 y, as a control group. Patients with multinodular goiter, single thyroid nodules, thyroiditis, pregnant women, and those on medications or oral contraceptives, were excluded. Result: clinical significance of FGF23 and Klotho (KL) levels in patients with Graves’ disease (GD) compared to a control group. Results indicate that the median of KL levels are significantly higher in GD patients (KL = 6.31) compared to the control group (KL = 2.40), with a highly significant difference (P &lt; 0.001). In contrast, differences in median of FGF23 levels between GD patients (149) and controls (86.05) were not statistically significant (P = 0.07). Furthermore, KL levels were significantly higher in hyperthyroid patients compared to other thyroid statuses (P = 0.023), while FGF23 levels did not significantly differ across thyroid statuses (P = 0.255). Additionally, the study found a strong correlation between TRAb levels and both KL (r = 0.291, P &lt; 0.001) and FGF23 (r = 0.211, P = 0.003), and between KL and FGF23 directly (r = 0.412, P &lt; 0.001). These findings suggest that while KL may be a significant biomarker in GD, FGF23 relevance appears limited in this context. Conclusion: In Graves’ Disease patients have significantly higher levels of KL and FGF23 compared to controls, suggesting a distinct pathophysiological role for these biomarkers in mineral homeostasis and thyroid hormone regulation. Abbreviations: AITD - Autoimmune thyroid diseases; KL - Alpha-Klotho; FGF23 - fibroblast growth factor-23; GD - Graves’ disease; HT - Hashimoto's thyroiditis; IGF-1R - Insulin-like Growth Factor-1 Receptor; Keywords: Autoimmune Thyroid Disorders, Hyperthyroidism, Graves’ disease, Alpha-Klotho Citation: Rashid MF, Alammar HAJ, Rahmah AM. Evaluation of alpha Klotho and fibroblast growth factor-23 levels in Iraqi patients with Graves’ disease. Anaesth. pain intensive care 2024;28(5):836−841. DOI: 10.35975/apic.v28i5.2567 Received: June 16, 2024; Reviewed: July 07, 2024; Accepted: July 18, 2024

Effects of Vitamin C on Aluminum Chloride- Induced Neurotoxicity on the Hippocampal Cortex of Adult Wistar Male Rats

This study aimed to evaluate the neuroprotective effects of Vitamin C on aluminum chloride (AlCl₃)- induced brain damage, focusing on behavioral, biochemical, and histomorphological outcomes in a rodent model. Study Design: A total of 42 healthy male rats were randomly assigned to three groups: control, AlCl₃ -only, and AlCl₃ plus Vitamin C (500 mg/kg and 1000 mg/kg). The AlCl₃ groups received daily doses of AlCl₃, while the Vitamin C groups received concurrent Vitamin C supplementation. Methodology: Body weight, behavioral changes, biochemical markers of oxidative stress (MDA, SOD, GSH), and inflammation (TNF-α, IL-6) were assessed. Histomorphological analysis of the hippocampus was performed to evaluate structural damage. Behavioral assessments included locomotor and exploratory activity tests. Biochemical analyses measured oxidative stress and antioxidant enzyme activities. Results: AlCl₃ administration resulted in significant body weight loss, increased oxidative stress (elevated MDA, and SOD levels), and heightened inflammation (elevated TNF-α and IL-6). Behavioral tests showed increased excitatory activities, and increased anxiety levels as seen in increased rearing and grooming activities. Histomorphological examination revealed significant hippocampal damages as seen in the pale staining, shrunken pyramidal cells. Vitamin C co- administration mitigated these adverse effects, demonstrating reduced body weight loss, lower oxidative stress, decreased inflammation, and improved behavioral performance. Histological analysis indicated less hippocampal damage in the Vitamin C treated groups. Conclusion: As an antioxidant, Vitamin C effectively attenuates the neurotoxic effects of AlCl₃ by reducing oxidative stress and inflammation, and by protecting the hippocampal cellular integrity. These findings suggest that Vitamin C holds potential as a therapeutic agent for mitigating neurotoxicity induced by aluminum compounds.

8631 Tanycytic TSHR Activation Regulates Blood-Hypothalamus Barrier Plasticity, Ingestive Behavior, Adipose Remodeling, and Body Weight

Abstract Disclosure: L. Cullen: None. H.S. Kannangara: None. R. Witztum: None. J. Burgess: None. S. Miyashita: None. A. Gumerova: None. F. Korkmaz: None. S.L. Sims: None. U. Cheliadinova: None. G. Pevnev: None. O. Moldavski: None. O. Barak: None. S. Rojekar: None. V. Laurencin: None. T. Frolinger: None. T. Yuen: None. K. Goosens: None. W. Zhou: None. V. Ryu: None. M. Zaidi: None. The notion that TSH acts solely on its primary endocrine target, the thyroid gland, has long been challenged (Abe et al., 2003; PMID: 14567913). More recently, however, we and others have used single transcript technology to document, for the first time, Tshr expression in over 173 brain regions and nuclei, particularly hypothalamic tanycytes (eLife, 2022, PMID: 36052994). The latter cells are known to convey metabolic information across the blood-hypothalamus barrier (BHB) and regulate energy homeostasis. To study whether tanycytic TSHRs have a role in the regulation of BHB permeability, ingestive behavior, adipose tissue remodeling and body weight, we first compared BHB vascular permeability of food-deprived and ad libitum-fed Tshr+/- mice and their wild type (WT) littermates. Transmission electron microscopy and immunostaining was used to study the expression of the constitutive tight junction protein claudin-1 and the glycoprotein MECA-32, which are expressed in tanycytes and endothelial cells, respectively. In loss-of-function studies, fasting of Tshr+/- mice and of WT mice significantly increased the organization of tanycytic honeycomb pattern of claudin-1 and MECA-32-associated fenestral diaphragms in the median eminence and arcuate nucleus, suggesting decreased BHB permeability. As a result, peanut butter consumption following fasting was decreased significantly compared to control mice. In gain-of-function studies, intracerebroventricular (ICV) infusions of a highly specific TSHR agonist, MS438, profoundly increased BHB permeability in fasted mice, as evidenced by decreased claudin-1 and MECA-32 immunostaining and significant increases in peanut butter consumption. This was associated with greater loss of fat mass and body weight following food deprivation, as well as increased influx of fatty acids across the BHB, increased NPY expression (as a measure of increased appetite), and increased secretion of ghrelin from the stomach fundus. We further performed c-Fos immunostaining in brain centers regulating ingestive behavior. ICV MS438 significantly decreased c-Fos immunoreactivity in the hypothalamic paraventricular nucleus, arcuate nucleus and the nucleus of the solitary tract. Early studies using CRSIPR/Cas9 to delete Tshrs in tanycytes via ICV injection resulted in reduced body weight following food deprivation. Finally, using PRV152 (injected into fat tissue) and PRV614 (injected into stomach fundus), we colocalized immunostaining in the hypothalamic paraventricular nucleus, and hindbrain raphe pallidus. Collectively, these data establish a new role for tanycytic TSHRs in regulating BHB plasticity, ingestive behavior, adipose tissue remodeling, and body weight through a novel fast-forward circuit involving the hypothalamus, stomach fundus and fat depots. Presentation: 6/3/2024

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.

Pharmacodynamic and pharmacokinetic study of Shaoyao Gancao decoction for repairing intestinal barrier damage in ulcerative colitis

ObjectiveTo study the therapeutic effect and mechanism of Shaoyao Gancao Decoction (SGD) on ulcerative colitis (UC) mice based on the perspective of intestinal barrier, and this study provides a new consultation for the clinical application of SGD. MethodsThe chemical composition of SGD was characterized by HPLC. The UC mouse model was constructed by 3 % dextran sodium sulfate (DSS), which were randomly divided into the model group (DSS), the positive drug group (5-ASA), the Shaoyao group (SYD), Gancao group (GCD), and the Shaoyao Gancao Decoction group (SGD) at low, medium, and high dosages, respectively. The effects of each drug treatment group on UC were evaluated by the rate of body weight loss, disease activity index (DAI), colon length, spleen index, histopathological evaluations, and the levels of serum inflammatory factors (IL-1β, IL-6, IL-10, IL-21, and TNF-α). The goblet cell was observed by Alcian blue/periodic acid-Schiff (AB/PAS) straining, ELISA was used to detect the content of LPS in serum, and Western blot was used to detect the changes in the expression of tight junction proteins ZO-1, occludin, and the pathway proteins TLR4 and NF-κBp65 in the colonic tissues, to explore the protective effect of SGD on the intestinal barrier of UC mice. The vivo absorption process of the main active ingredients in the SG, SY and GC groups was determined by LC-MS. ResultsThe contents of albiflorin, paeoniflorin, liquiritin apioside, liquiritin and glycyrrhetinic acid were 6.1227 mg/g, 20.8993 mg/g, 4.0054 mg/g, 3.6140 mg/g and 8.2515 mg/g, respectively. Compared with DSS group, SGD reduced weight loss(P<0.01) and DAI scores(P<0.05), prevented colon shortening(P<0.01), and ameliorated histopathological damage of the colon in UC mice(P<0.01). SGD also protected the intestinal barrier to alleviate UC by significantly reducing serum LPS and inflammatory factor levels, altering the number of goblet cells, promoting tight junction proteins (ZO-1 and occludin) and decreasing the expression of TLR4 and NF-κB in colonic tissues. Pharmacokinetic results showed that there was no significant difference in Cmax, AUC0-t (μg/L.h) and Tmax of albiflorin and paeoniflorin between the SY and SG groups, the Tmax was within 1 h; the AUC0-t (μg/L.h) of liquiritin and glycyrrhizic acid were about 1.6 and 1.9 times higher in the SG group compared to the GC group, respectively. The Cmax, Tmax and AUC0-t (μg/L.h) of glycyrrhizinic acid were significantly reduced to 0.73, 0.68 and 0.68 times of that of the GC group. ConclusionSGD may have a therapeutic effect on DSS-induced UC mice by repairing the damaged intestinal barrier through the TLR4/NF-κB pathway. The combination of Shaoyao and Gancao increased the absorption of liquiritin and glycyrrhizic acid in vivo. The combination of Shaoyao and Gancao could promote the absorption of Gancao, and that the pairing of the two herbs could have a synergistic effect.

6926 Subgroup Analysis by Gender and Body Mass Index (BMI) in People Living With Overweight/Obesity in the Survodutide, a Glucagon/GLP-1 Receptor Dual Agonist, Phase II Trial

Abstract Disclosure: C.W. Le Roux: Consulting Fee; Self; Boehringer Ingelheim, Novo Nordisk, GI Dynamics, Herbalife, Johnson &amp; Johnson, Eli Lilly, Keyron. O. Steen: Consulting Fee; Self; Eli Lilly &amp; Company, Novo Nordisk, Sanofi. Grant Recipient; Self; Alnylam, Anji, AstraZeneca, Boehringer Ingelheim, Eli Lilly &amp; Company, Janssen, Genzyme Corporation, Medacorp, Novo Nordisk, Medicago, Moderna, Novavax, Pfizer, Sanofi, Zucara Therapeutics, Gilead, ViaCyte, CRISPR Therapeutics, Kowa. Speaker; Self; Amgen Inc, AstraZeneca, Bausch Health, Janssen, LMC, Novo Nordisk. K.J. Lucas: None. E. Startseva: Employee; Self; Boehringer Ingelheim. A. Unseld: Employee; Self; Boehringer Ingelheim. A.M. Hennige: Employee; Self; Boehringer Ingelheim. Aim: To explore the effect of gender and BMI on weight loss and adverse events with survodutide in people living with overweight/obesity. Methods: In this double-blind, placebo (PBO)-controlled Phase II trial (NCT04667377), 387 adults with BMI ≥27 kg/m2 without diabetes were randomized 1:1:1:1:1 to weekly subcutaneous survodutide (0.6, 2.4, 3.6, 4.8 mg) or PBO over 46 weeks. Percentage change in body weight (primary endpoint), absolute change in body weight and waist circumference (secondary endpoints), and adverse events (AEs) were assessed in subgroups based on gender and BMI at baseline (BL). Data were analyzed descriptively for all participants who received ≥1 dose of study drug and had data for ≥1 efficacy endpoint (full analysis set [FAS]; planned treatment: n=384). Results: Of 384 participants, 68.2% (262) were female. At BL, 9.9% (38), 30.5% (117), 31.8% (122), and 27.9% (107) had a BMI of &amp;lt;30, 30-&amp;lt;35, 35-&amp;lt;40, and ≥40 kg/m2, respectively. Demographics and clinical characteristics at BL were similar between males and females and across BMI subgroups. At Week 46, mean percentage change in body weight from BL with survodutide 4.8 mg vs PBO was -11.9% vs -3.3% in males and -17.0% vs -3.2% in females, and -19.1% vs -1.7%, -15.8% vs -3.1%, -15.4% vs -5.8%, and -13.4% vs -0.8% across BL BMI categories. Mean absolute body weight loss from BL (survodutide 4.8 mg vs PBO) was -15.9 vs -4.2 kg in males and -22.0 vs -3.0 kg in females. Reductions in absolute body weight with survodutide 4.8 mg vs PBO were similar across BMI subgroups: -21.3 vs 1.4 kg, -16.2 vs -3.3 kg, -22.2 vs -7.5 kg, and -19.9 vs -1.6 kg. Mean absolute change in waist circumference from BL (survodutide 4.8 mg vs PBO) was -12.8 vs -1.7 cm in males and -17.9 vs -4.9 cm in females, and -8.4 vs -2.6 cm, -14.3 vs -6.4 cm, -17.5 vs -5.0 cm, and -17.2 vs 3.3 cm across BL BMI categories. A higher proportion of participants lost ≥15% of BL body weight with survodutide 4.8 mg vs PBO: 31.8% vs 9.5% in males and 66.7% vs 3.0% in females, and 75.0% vs 14.3%, 57.9% vs 4.5%, 52.0% vs 6.7%, and 50.0% vs 0.0% across BL BMI categories; respectively. All survodutide doses (pooled) were tolerated as expected across gender and BL BMI subgroups. In males vs females, respectively, rates of any AE (87.9% vs 92.4%), serious AEs (4.0% vs 4.3%), and discontinuations due to AEs (25.3% and 24.3%) were comparable. Gastrointestinal (GI) AEs with all survodutide doses were experienced by fewer males (65.7%) than females (79.5%); mild to moderate nausea was the most frequently reported GI AE in both subgroups. Conclusion: After 46 weeks of survodutide treatment, females appeared to lose more body weight and waist circumference than males. Participants with a lower vs higher BL BMI generally lost more proportional body weight, with an opposite trend observed for waist circumference. Presentation: 6/2/2024

Use of Precision Feeding during Lactation Improves the Productive Yields of Sows and Their Piglets under Commercial Farm Conditions.

Adequate nutritional management in maternities is one of the most challenging aspects of swine production. This study reports the results of two studies aiming to determine, under commercial farm conditions, the effects of precision feeding (electronic sow feeders, ESFs) on the production and economic yields of lactating sows and possible nutritional and metabolic differences when compared to a control group fed with traditional feeders. The first trial showed that sows fed with ESFs weaned heavier piglets than sows fed with traditional feeders. Feed intake during the lactation period was similar in the sows of both groups; consequently, the amount of feed per kg of weaned piglet was lower in the sows fed with ESFs, which is a remarkable economic output. The second trial confirmed these findings and showed that, despite similar feed intakes, the sows fed with ESFs had lower bodyweight losses during the lactation period, but there were no major differences in milk composition or metabolic traits of sows and piglets.

CT584 Is Not a Protective Vaccine Antigen against Respiratory Chlamydial Challenge in Mice.

Background:Chlamydia trachomatis is the most prevalent bacterial sexually transmitted pathogen in humans worldwide. Since chlamydial infection is largely asymptomatic with the potential for serious complications, a preventative vaccine is likely the most viable long-term answer to this public health threat. Cell-free protein synthesis (CFPS) utilizes the cellular protein manufacturing machinery decoupled from the requirement for maintaining cellular viability, offering the potential for flexible, rapid, and decentralized production of recombinant protein vaccine antigens. Methods: Here, we use CFPS to produce the full-length putative chlamydial type three secretion system (T3SS) needle-tip protein, CT584, for evaluation as a vaccine antigen in mouse models. High-speed atomic force microscopy (HS-AFM) (RIBM, Tsukuba, Japan) imaging and computer simulations confirm that CFPS-produced CT584 retains a native-like structure prior to immunization. Female mice were primed with CT584 adjuvanted with CpG-1826 intranasally (i.n.) or CpG-1826 + Montanide ISA 720 intramuscularly (i.m.), followed four weeks later by an i.m. boost before respiratory challenge with 104 inclusion forming units (IFU) of Chlamydia muridarum. Results: Immunization with CT584 generated robust antibody responses but weak cell-mediated immunity and failed to protect against i.n. challenge as demonstrated by body weight loss, increased lung weights, and the presence of high numbers of IFUs in the lungs. Conclusion: While CT584 was not a protective vaccine candidate, the speed and flexibility with which CFPS can be used to produce other potential chlamydial antigens make it an attractive technique for antigen production.

Weight loss as a predictor of reduced survival in patients with lung cancer: a systematic review with meta-analysis.

The impact of weight loss on survival outcomes remains challenging in patients with lung cancer. The objective of this systematic review with meta-analysis was to assess the association of weight loss with survival outcomes in these patients. Two authors conducted a comprehensive literature search of PubMed, Web of Science, and Embase databases up to January 15, 2024. Observational studies that assessed the weight loss as a prognostic factor of overall survival and progression-free survival in patients with lung cancer were included this analysis. Weight loss defined by at least 5% loss of total body weight over 2 months. Fifteen studies involving 14,540 patients with lung cancer were included. Pooled adjusted hazard ratios (HR) indicated that weight loss was associated with reduced overall survival (HR 1.65; 95% confidence intervals [CI] 1.43-1.91) and progression-free survival (HR 1.40; 95% CI 1.15-1.71). Subgroup analysis showed that weight loss significantly predicted overall survival, regardless of study design, lung cancer subtypes, clinical stage of cancer, weight loss definition, or length of follow-up. Weight loss is a significant predictor of overall survival and progression-free survival in patients with lung cancer. Weight monitoring has potential to improve prognostication of survival outcomes for these patients.

Low serum glycine strengthens the association between branched-chain amino acids and impaired insulin sensitivity assessed before and after weight loss in a population with pre-diabetes: The PREVIEW_NZ cohort

AimAccumulation of circulating branched-chain amino acids (BCAA) is a hallmark feature of impaired insulin sensitivity. As intracellular BCAA catabolism is dependent on glycine availability, we hypothesised that the concurrent measurement of circulating glycine and BCAA may yield a stronger association with markers of insulin sensitivity than either BCAA or glycine alone. This study therefore examined the correlative relationships of BCAA, BCAA and glycine together, plus glycine alone on insulin sensitivity-related markers before and after an 8-week low energy diet (LED) intervention. MethodsThis is a secondary analysis of the PREVIEW (PREVention of diabetes through lifestyle Intervention in Europe and Worldwide) Study sub-cohort. Eligible participants with pre-diabetes at baseline who achieved ≥8% body weight loss following an LED intervention were included, of which 167 paired (Week 0 and Week 8) blood samples were available for amino acid analysis. Glycemic and other data were retrieved from the PREVIEW consortium database. Repeated measures linear mixed models were used to test the association between amino acids and insulin sensitivity-related markers (HOMA2-IR, glucose, insulin, and C-peptide). ResultsElevated BCAA was associated with impaired insulin sensitivity (p < 0.05), with strength of association (ηp2) almost doubled when glycine was added to the model. However, glycine in isolation was not associated with insulin sensitivity-related markers. The magnitude (β-estimates) of positive association between BCAA and HOMA2-IR, and inverse association between glycine and HOMA2-IR, increased when body weight was higher (Body weight*BCAA, Body weight*glycine, p < 0.05, both). ConclusionLow serum glycine strengthened the association between BCAA and impaired insulin sensitivity. Given that glycine is necessary to facilitate intracellular BCAA catabolism, measurement of glycine is necessary to complement BCAA analysis to comprehensively understand the contribution of amino acid metabolism in insulin sensitivity. Clinical Trial RegistrationThis study was registered with ClinicalTrials.gov (NCT01777893).

Safety and Effectiveness of Two Different Fluid-Filled Intragastric Balloons: A Single Center Experience.

The aim of the study is to compare weight loss and safety outcomes of two different commonly available fluid-filled intragastric balloons (IGBs) used for weight loss. A retrospective cohort study of a prospectively maintained database of adult patients who underwent IGB insertion between July 2020 and November 2021 in a single private clinic in Kuwait. The patient either received the Elipse™ or Orbera365™ balloon and was followed until the end of treatment. A total of 358 patients were included, of which 265 and 93 each received the Elipse and Orbera365 balloons, respectively. The mean age of patients was 32.8 (SD 9), the mean body mass index (BMI) was 35kg/m2 (SD 4.8), and 72.1% of patients were female. In the Elipse group, 254 patients completed treatment, and 84 patients completed the treatment with Orbera365. Weight loss outcomes were measured at the end of treatment: 4months after Elipse insertion, and 12months after Orbera365 insertion. Interim 4months weight loss outcomes were also measured for the Orbera365 balloon. Patients in the Orbera365 group had significantly better total body weight loss (%TBWL, 14.7kg [SD 8.9]) compared to the Elipse group (%TBWL 10kg, [SD 5.6], p ≤ 0.0001) at the end of treatment, while there was no difference in weight loss outcomes between the two balloons at 4months. There were more complications requiring premature balloon removal in the Orbera365 group (9.7%) compared to the Elipse group (3.4%). IGBs provide significant weight loss with an acceptable safety profile. The Orbera365 ballon shows better weight loss outcomes compared to the Elipse, likely due to longer duration of treatment. However, there was a higher rate of complications requiring premature balloon removal in the Orbera365 group. Studies with larger patient cohort is needed to verify the findings of this study.

Beneficial effect of Caesalpinia pulcherrima Linn., on diabetic neuropathy, cognitive dysfunction and cardiac complications in streptozotocin-induced diabetic rats

Pharmacological relevanceCaesalpinia pulcherrima L. is used in Indian Traditional Medicinal system to treat Diabetes. AimThis study was carried out to evaluate the standardized alcoholic extract of Caesalpinia pulcherrima seed (CPS) in Streptozotocin (STZ)-induced diabetic neuropathic and cardiac complications in rodents. Materials and methodsHPLC finger printing profile of CPS was performed to identify the bioactive molecules. Two doses of CPS (100 & 200 mg/kg b.w.) was orally administered daily once for six weeks to streptozotocin (50 mg/kg, i.v.)-induced diabetic rats. Every week intervals hot & cold immersion tests were carried to know the effect of CPS on peripheral neuropathy. In addition, blood glucose, body weight, food and water intake were also monitored. At the end of the study, sciatic nerve conduction velocity, diabetic cardiomyopathy and diabetic cognitive parameters were evaluated. Furthermore, histopathological studies of sciatic nerve and aortic strip were also carried out. ResultsHPLC finger print experiment showed the presence of gallic acid and protocatechuic acid. Administration of CPS for six weeks significantly prevented the development of diabetic peripheral neuropathy (DPN), cardiomyopathy and cognitive dysfunction in diabetic rats. The CPS treated rats displayed prominent (P<0.001) improvement in motor coordination, muscle grip, locomotor activity and memory in diabetic rats. CPS treatment restored elevated systolic, diastolic, mean arterial blood pressure (MABP), and heart rate to near normal in diabetic condition. These observed beneficial effects were well correlated and justified with histopathological studies. In addition, CPS treatment also exhibited significant (P<0.001) reduction of loss in body weight, and reduce the water and feed intake throughout the study. ConclusionTaken together, the present study provided a good insight in the therapeutic efficacy of Caesalpinia pulcherrima seed extract in dealing with diabetic complications. The study also scientifically justifies the ethnomedicinal/traditional claims of the title plant.

Regulatory effects of the p38 mitogen-activated protein kinase-myosin light chain kinase pathway on the intestinal epithelial mechanical barrier and the mechanism of modified Pulsatilla decoction in the treatment of ulcerative colitis.

To investigate the mechanism of the protective effect of modified Pulsatilla decoction (, MPD) on the mechanical barrier of the ulcerative colitis (UC) intestinal epithelium in vitro and in vivo. We established an intestinal epithelial crypt cell line-6 cell barrier injury model by using lipopolysaccharide (LPS). The model was then treated with p38 mitogen-activated protein kinase-myosin light chain kinase (p38MAPK-MLCK) pathway inhibitors, p38MAPK-MLCK pathway silencing genes (si-p38MAPK, si-NF-κB, and si-MLCK), and MPD respectively. Transepithelial electronic resistance (TEER) measurements and permeability assays were performed to assess barrier function. Immunofluorescence staining of tight junctions (TJ) was performed. In in vivo experiment, dextran sodium sulfate-induced colitis rat model was conducted to evaluate the effect of MPD and mesalazine on UC. The rats were scored using the disease activity index based on their clinical symptoms. Transmission electron microscopy and hematoxylin-eosin staining were used to examine morphological changes in UC rats. Western blotting and real-time quantitative polymerase chain reaction were performed to examine the gene and protein expression of significant differential molecules. In in vitro study, LPS-induced intestinal barrier dysfunction was inhibited by p38MAPK-MLCK pathway inhibitors and p38MAPK-MLCK pathway gene silencing. Silencing of p38MAPK-MLCK pathway genes decreased TJ expression. MPD treatment partly restored the LPS-induced decreased in TEER and increase in permeability. MPD increased the gene and protein expression of TJ, while down-regulated the LPS-induced high expression of p-p38MAPK and p-MLC. In UC model rats, MPD could ameliorate body weight loss and disease activity index, relieve colonic pathology, up-regulate TJ expression as well as decrease the expression of p-p38MAPK and p-MLC in UC rat colonic mucosal tissue. The p38MAPK-MLCK signaling pathway can affect mechanical barrier function and TJ expression in the intestinal epithelium. MPD restores TJ expression and attenuates intestinal epithelial barrier damage by suppressing the p38MAPK-MLCK pathway.

Impact of Cachexia and First-Line Systemic Therapy for Previously Untreated Advanced Non-Small Cell Lung Cancer: NEJ050A.

Cancer cachexia complicates advanced non-small cell lung cancer (NSCLC); however, it remains unclear how often cachexia occurs and how it affects the course of chemotherapy in patients receiving first-line systemic therapy. We conducted a multicentre, prospective observational study and enrolled previously untreated NSCLC patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2 and cachexia between September 2020 and September 2021. The primary outcome measure was the trends in the Functional Assessment of Anorexia/Cachexia Treatment and Anorexia/Cachexia Subscale [FAACT (A/CS)] scores by cohort. Secondary outcome measures included the incidence of cachexia before the initiation of first-line systemic therapy, quality of life (QOL) measures, body weight (BW) changes, and efficacy and safety of first-line systemic therapy. A total of 887 consecutive patients with previously untreated advanced NSCLC and ECOG PS of 0-2 who were initiated on first-line systemic therapy were evaluated. A total of 281 patients (31.7%) experienced BW loss consistent with the criteria of cachexia, and 186 were evaluated for QOL, BW and outcome measurements. Overall, 180/186 patients received first-line systemic therapy. Cohort 1 (targeted therapy), cohort 2 [cytotoxic chemotherapy (CTx) ± immune checkpoint inhibitors (ICIs)] and cohort 3 (ICIs) included 42, 98 and 40 patients, respectively. There were significant variations in QOL trends by cohort, with chemotherapy-associated emesis affecting early appetite-related QOL. The change in the FAACT (A/CS) score at 1 week from baseline was worse in cohort 2 (the least square mean change ± standard error: -3.0 ± 0.9) than in cohorts 1 (1.6 ± 1.2, p = 0.003) and 3 (1.8 ± 1.0, p = 0.002); meanwhile, the change at 6 weeks was worse in cohort 1 (-1.5 ± 1.2) than in cohorts 2 (3.6 ± 0.9, p = 0.001) and 3 (3.5 ± 1.1, p = 0.004). BW reduction was observed in all cohorts within 6 weeks of therapy initiation. The targeted therapy cohort demonstrated superior progression-free survival (PFS) and overall survival (OS) to CTx ± ICIs cohort or ICIs cohort (median PFS was 9.7 months, 6.3 months, 3.1 months, in cohort 1, 2, 3, respectively (cohort 1 vs. cohort 2: HR, 0.58, p = 0.018; cohort 1 vs. cohort 3: HR, 0.41, p = 0.001); median OS was not reached, 15.8 months, 9.9 months, respectively (cohort 1 vs. cohort 2: HR, 0.52, p = 0.033; cohort 1 vs. cohort 3: HR, 0.37, p = 0.003). Approximately 1/3 patients with previously untreated advanced NSCLC have cachexia. Appetite-related QOL trends vary based on the type of first-line systemic therapy in cachectic NSCLC patients, and the PFS and OS of these patients seemed to be shorter.

Supplementing pigeon grit with acidifier improves metabolism and the reproductive performance of breeding pigeons as well as the development of growth performance of squabs

ABSTRACT 1. This study evaluated the effectiveness of different types of acidifiers on reproductive performance, body weight loss and plasma biochemical indices of breeding pigeons as well as on growth performance, carcass characteristics, meat quality and plasma biochemical indices of squabs. 2. In a 45 d trial, 144 pairs of European white Mimas pigeons were selected and randomly divided into three experimental groups. Three groups of pigeons were fed plain pigeon grit (NC), pigeon grit supplemented with 5% single acidifier (SAG) and pigeon grit supplemented with 5% combined acidifiers (CAG). 3. Supplementing with SAG and CAG significantly increased the weight gain in male pigeons from 1-12 d of incubation. However, SAG and CAG had no significant effect on the feed intake of breeding pigeons during incubation, but significantly increased total feed intake of breeding pigeons during the lactation period. Breeder pigeons fed SAG and CAG had significantly higher egg-laying rate at 40 d. In addition, feeding SAG and CAG significantly increased growth rate and slaughter weight of squabs, but SAG reduced the diameter of pectoral muscle fibres. Biochemical indices showed that feeding SAG and CAG improved metabolism and increased the liver function of breeder pigeons and squabs. 4. In conclusion, supplementing pigeon grit with acidifiers increased feed intake of breeding pigeons during lactation, protected liver function, enhanced reproductive performance and promoted the growth and development of squabs.

A Systematic Review and Meta-Analysis of the Effect of Caloric Restriction on Skeletal Muscle Mass in Individuals with, and without, Type 2 Diabetes.

Severe caloric restriction interventions (such as very-low-calorie diets) are effective for inducing significant weight loss and remission of type 2 diabetes (T2DM). However, suggestions of associated significant muscle mass (MM) loss create apprehension regarding their widespread use. We conducted a systematic review and meta-analysis to provide a quantitative assessment of their effect on measures of MM in individuals with, or without, T2DM. EMBASE, Medline, Pubmed, CINAHL, CENTRAL and Google Scholar were systematically searched for studies involving caloric restriction interventions up to 900 kilocalories per day reporting any measure of MM, in addition to fat mass (FM) or body weight (BW). Forty-nine studies were eligible for inclusion, involving 4785 participants. Individuals with T2DM experienced significant reductions in MM (WMD -2.88 kg, 95% CI: -3.54, -2.22; p < 0.0001), although this was significantly less than the reduction in FM (WMD -7.62 kg, 95% CI: -10.87, -4.37; p < 0.0001). A similar pattern was observed across studies involving individuals without T2DM. MM constituted approximately 25.5% of overall weight loss in individuals with T2DM, and 27.5% in individuals without T2DM. Subgroup analysis paradoxically revealed greater BW and FM reductions with less restrictive interventions. Our review suggests that caloric restriction interventions up to 900 kilocalories per day are associated with a significant reduction in MM, albeit in the context of a significantly greater reduction in FM. Furthermore, MM constituted approximately a quarter of the total weight loss. Finally, our data support the use of less restrictive interventions, which appear to be more beneficial for BW and FM loss.

A Pilot Study of an Endoluminal-Suturing Device as a Treatment Strategy for Patients With Obesity and Obstructive Sleep Apnea

Background and Objective Obstructive sleep apnea (OSA) is a multifactorial disease, and obesity is the most prevalent risk factor for OSA. Endoscopic sleeve gastroplasty (ESG) is a minimally-invasive procedure used for treating obesity. This prospective study tested the potential benefit of weight loss via an ESG device, endomina&lt;sup&gt;®&lt;/sup&gt;, for reduction of apnea-hypopnea index (AHI) in patients with class I obesity and severe OSA.Methods Ten patients with BMI values of 28 to 34.9 kg/m&lt;sup&gt;2&lt;/sup&gt; and severe OSA underwent ESG and lifestyle management for 6 months. Patients underwent polysomnography before and 6 months after the endoscopic procedure. The primary endpoint was the percentage of AHI reduction six months after the endoscopic procedure. Secondary endpoints were the proportion of patients with AHI reductions of 50% six months after ESG, improvements in respiratory parameters and sleepiness, effectiveness on weight loss, and correlations with decreased AHI.Results Patients experienced 54% (±11%) reductions in AHI. Seven patients had an AHI reduction of ≥50%, and five had an AHI of &lt;15 events/h. Total body weight loss (TBWL) and excess weight loss (EWL) were 10.1% (±3.4%) and 45.4% (±14.0%), respectively, and there was no correlation between AHI and TBWL/EWL. There was an overall improvement in respiratory sleep parameters after ESG, except for snoring, and a reduction in daytime sleepiness.Conclusions These results suggest that using an ESG device, endomina&lt;sup&gt;®&lt;/sup&gt;, with lifestyle modification for promoting weight loss in class I obese patients with severe OSA is a promising treatment strategy for reducing OSA and improving respiratory parameters and daytime sleepiness.