Weight Index Research Articles

The mitigating effect of para-hydroxycinnamic acid in bleomycin-induced pulmonary fibrosis in mice through targeting oxidative, inflammatory and fibrotic pathways.

This study investigated the therapeutic benefits of para-hydroxycinnamic acid in mice with bleomycin-induced lung fibrosis. Forty male BALB/c mice were randomly assigned to four groups: normal, which received 0.9% normal saline; induced, which received a single dose of bleomycin (5mg/kg) by oropharyngeal challenge; pirfenidone-treated; and para-hydroxycinnamic acid-treated, which challenged with bleomycin and received a daily oral dose of 300 and 50 mg/kg, respectively, from day 7 to day 21. Tissue pro-fibrotic and inflammatory cytokines, oxidative indicators, pulmonary histopathology, immunohistochemistry of fibrotic proteins and the assessment of gene expression by RT-qPCR were evaluated on day 22 after euthanizing animals. Pirfenidone and para-hydroxycinnamic acid managed to alleviate the fibrotic endpoints by statistically improving the weight index, histopathological score and reduced expression of fibrotic-related proteins in immune-stained lung sections, as well as fibrotic markers measured in serum samples. They also managed to alleviate tissue levels of oxidative stress and inflammatory and pro-fibrotic mediators. para-Hydroxycinnamic acid enhanced the expression of crucial genes associated with oxidative stress, inflammation and fibrosis in vivo. para-Hydroxycinnamic acid has demonstrated similar effectiveness to pirfenidone, suggesting it could be a promising treatment for fibrotic lung conditions by inhibiting the TGF-β1/Smad3 pathway or through its anti-inflammatory and antioxidant properties.

Translation, cross-cultural adaptation, and validation of the Duke Activity Status Index (DASI) to Sinhala language

BackgroundDuke Activity Status Index (DASI) is a widely used tool to assess functional capacity among patients, but there is no Sinhala version validated for patients in Sri Lanka. This study aimed to cross-culturally adapt and test the validity and reliability of the Sinhala version of DASI (DASI-S).MethodsThe translation and cross-cultural adaptation of the DASI questionnaire were conducted following the standard guidelines. It was pre-tested on ten pre-operative patients and further modified. The construct validity and reliability of DASI-S were evaluated by administering the modified final DASI-S, which comprised 12 items, along with the physical functioning sub-scale of the 36-item short-form health survey (SF-36), consisting of 10 items to eighty-one patients who were awaiting non-cardiac surgeries at university surgical wards, National Hospital of Sri Lanka (NHSL), and Colombo North Teaching Hospital (CNTH), Sri Lanka. Reliability was assessed through Cronbach alpha, while the validity was evaluated using factor analysis and Spearman’s correlation. The ethical approval was obtained from the Ethics Review Committee, Faculty of Medicine, University of Colombo, Sri Lanka.ResultsThe mean age of the participants was 46.2 (± 16.6) years and the majority were females (54.3%). The mean height, weight, and body mass index of the sample were 160.5 (± 9.6) cm, 60.3 (± 11.9) kg, and 23.4 (± 4.5) kgm−2 respectively. The Cronbach's alpha coefficient for the internal consistency of DASI-S was 0.861. The concurrent validity of DASI-S was substantiated by positively correlating (p < 0.01, rs = 0.466) with the physical sub-scale of SF-36. There was a significant difference (p < 0.01) in the total score of DASI-S between the two age groups.ConclusionsSinhala version of the DASI appears to be a valid, reliable and easy-to-administer tool to assess functional capacity among patients who are awaiting non-cardiac surgeries.

Beneficial Effects of Echinacoside on Cognitive Impairment and Diabetes in Type 2 Diabetic db/db Mice.

Cognitive dysfunction is an important comorbidity of diabetes. Insulin resistance may play a critical role in diabetes-related cognitive impairment. Echinacoside (ECH), a natural phenylethanoid glycoside, is the active component of anti-diabetes prescriptions in traditional Chinese medicine. Its effect on modulating insulin resistance has been confirmed but modulating neurodegenerative disease remains unclear. Db/db mice, a spontaneous type 2 diabetes mode, were intragastrically administered ECH by 300 mg/kg or an equivalent volume of saline. Weight, blood glucose, and insulin resistance index were measured. Morris water maze test was performed to observe the compound effects on cognition. Hippocampal lesions were observed by histochemical analysis. In db/db mice, ECH alleviated diabetes symptoms, memory loss, and hippocampal neuronal damage. Next, the expression of CD44 and phosphorylated tau was upregulated in diabetic mice. In addition, the insulin receptor substrate-1/phosphatidylinositol 3-kinase /protein kinase B signaling pathway was dysregulated in diabetic mice. All these dysregulations could be reversed by ECH. This study provides theoretical support and experimental evidence for the future application of ECH in diabetic cognition dysfunction treatment, promoting the development of traditional medicines.

Effects of osteoarthritis grades on pain, function and quality of life.

Osteoarthritis (OA) is a pathology that frequently affects the geriatric population. To investigate the extent to which pain, functionality, and quality of life change over the progression of OA grades. The study included 161patients with bilateral OA, whose disease stages ranged from 1 to 4according to the Kellgren-Lawrence radiographic classification system. Pain was assessed using the Visual Analog Scale (VAS), functionality using the two-minute walk test and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, and quality of life using the Nottingham Health Profile (NHP). There were significant differences between the groups in terms of age, weight, and body mass index. The VAS, two-minute walk test, and WOMAC scores also significantly differed between the groups (p< 0.05). There was a significant difference between the groups in all domains of the NHP, except for energy (p< 0.05). The two-minute walk test score was negatively correlated with all the remaining evaluation parameters (p< 0.05). No correlation was found between the energy domain of the NHP and body mass index, the VAS score, the two-minute walk test distance, or the total WOMAC score (p> 0.05). After grade1, the functional impacts of OA on patients increased by an average of four times. Pain was one of the most basic symptoms, the severity of which started to increase in grade2. With the added effect of diminishing walking capacity over time, the reduction in the quality of life of the patients accelerated as the OA grade progressed.

Physical growth and body weight index of children of Darhan-Uul province

The aim of the study is to examine the progress of physical growth and body mass index of children in Darkhan-Uul province relevant socio-economic factors , and the phenomenon of early acceleration. The findings of our research present that children living in apartments, which provide comfortable living condition and environment, are more advanced than their peers who lived in the ger district in their middle and last stages of growth. Social and economic factors, such as housing conditions and the number of family members had feasible impacts on the physical growth. Since the economic transition of the 1990s, the increase in the main indicators of the physical growth and development shows the acceleration phenomenon among the children in Darkhan-Uul province.

Evaluation of Reproductive and Growth Performance in New Breeds and Hybrids of Bivoltine Silkworm (Bombyx mori L.)

This study aimed to evaluate the reproductive and growth performance of recently developed bivoltine silkworm parental breeds and their hybrids to improve silk production and ensure the long-term sustainability of sericulture. Utilizing five thermotolerant pure breeds (B1, B2, B4, B6 and B8) and four popular CSR breeds (CSR2, CSR27, CSR6 and CSR26), six foundation crosses and eight double hybrids were developed and evaluated for ten traits. Results showed that B1 exhibited superior performance in fecundity (524.00), hatching percentage (98.67%), dead eggs (1.33%), pupal weight (1.31 g), pupation rate (96.84%) and cumulative survival index (CSI) (93.84%). The foundation cross B1 × B2 excelled in fecundity (553.67), larval mortality (2.67%), pupal weight (1.53 g), ERR (97.33%) and CSI (93.27%) while FC2 performed better in hatching percentage (97.60%), dead eggs percentage (2.40%), fifth instar larval duration (157.21 h), fifth instar larval weight (35.64 g/10 larvae) and pupation rate (96.33%). Among the double hybrids, (B1 × B2) × (FC1) demonstrated superior performance in fecundity (614.33), larval mortality (1.41%), pupal weight (2.06 g), ERR (98.59%) and CSI (97.24%). FC2 × FC1 excelled in larval duration (141.11 h), fifth instar larval weight (51.96 g/10 larvae) and pupation rate (98.94%). Double hybrids showed significant improvements compared to parental breeds and foundation crosses, indicating potential for field testing and further development. These results indicate the potential of using the newly identified breeds and foundation crosses in silkworm breeding, particularly in developing new double hybrids as an alternative to established CSR breeds and hybrids.

Clinical impact of sarcopenia on long-term mortality in patients undergoing coronary bypass grafting

Abstract Funding Acknowledgements None. Aims Sarcopenia is an aging-related condition characterized by loss of skeletal muscle mass and is an indicator of subclinical atherosclerosis. The relationship between sarcopenia and long-term clinical outcomes in patients with advanced coronary artery disease who have undergone coronary artery bypass grafting (CABG) is not fully understood. We evaluated the prognostic implications of sarcopenia in patients undergoing CABG. Methods and Results A total of 2,810 patients who underwent CABG was analyzed and classified according to presence of sarcopenia. The skeletal muscle index (SMI) was calculated as L3 muscle area (cm2)/height (m)2 on computed tomography. Sarcopenia was defined as SMI ≤45 cm2/m2 in men and ≤38 cm2/m2 in women. The primary outcome was all-cause mortality during follow-up. The median follow-up was 8.7 years, and 924 patients (32.9%) had sarcopenia. Patients with sarcopenia were older and more frequently women. SMI was significantly correlated with age (R=-0.34, P&amp;lt;0.001), weight (R=-0.56, P&amp;lt;0.001), and body mass index (R=-0.52, P&amp;lt;0.001). SMI was significantly associated with risk of death on a restricted cubic spline curve (HR=1.04 per-1 decrease, 95% CI 1.03-1.05, P&amp;lt;0.001). Patients with sarcopenia had a higher incidence of long-term mortality than those without sarcopenia (survival rate 41.4% vs. 62.8%; adjusted HR=1.18, 95% CI 1.03-1.36, P=0.02). Subgroup analysis showed that the prognostic implication of sarcopenia on long-term survival was more evident in men (adjusted HR=2.01, 95% CI 1.72-2.35) than women (adjusted HR=1.28, 95% CI 0.98-1.68) (interaction P=0.006). Conclusions Sarcopenia, defined by SMI on computed tomography, was associated with long-term mortality after CABG.

Anti-aging mechanism and effect of treatment with raw and wine-steamed Polygonatum sibiricum on D-galactose-induced aging in mice by inhibiting oxidative stress and modulating gut microbiota

BackgroundPolygonatum sibiricum (PS) is a traditional Chinese medicine (TCM) first recorded in Mingyi Bielu. The book documents that PS can nourish five internal organs, be taken for a long time, relax the body and prolong lifespan. Presently, PS is widely used in TCM to prevent premature graying of hair. Based on TCM theory and clinical trials, the wine steaming processed product from PS provides a better effect. However, no published study has elucidated the anti-aging mechanism.PurposeThe study aim was to investigate the anti-aging mechanism of PS and its wine steaming processed product in mice, specifically focusing on the effect of D-galactose (D-gal) surrounding the intestinal flora and the Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2-antioxidant response elements (Keap1/Nrf2/ARE) pathway.MethodsThe chemical components in Raw PS (RPS) and Wine-steamed PS (WPS) were identified by ultra-performance liquid chromatography–hybrid quadrupole-Orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS). An aging model using Kunming mice was established through intraperitoneally injected D-gal. Concentrations of RPS and WPS at 5, 10, or 15 g/kg/day levels were administered intragastrically, respectively. The body weight, liver and spleen indexes, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) activities in serum and brain tissue were recorded. Hematoxylin and eosin (HE) stained brain tissue was histopathologically examined. The expressions of Keap1, Nrf2 and heme oxygenase 1 (HO-1) in the brain tissue at the mRNA and protein levels were respectively detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB). Moreover, an Illumina Hiseq platform was used for 16S ribosomal RNA (16S rRNA) high-throughput sequencing to evaluate the proportions of intestinal flora in aging mice.ResultsThe proportions of saccharides, flavonoids, and triterpene acids were different between RPS and WPS. In the aging model mice, WPS outperformed RPS in improving body weight and mental state by increasing the spleen index, SOD and GSH-PX activities, decreasing the liver index and MDA activities, and restoring the histopathological morphology in D-gal-induced aging mice. At the mRNA levels, RPS and WPS significantly reduced the expression of Keap1 and increased the expressions of Nrf2 and HO-1. The trend in protein expressions was similar to that of the mRNA results, and WPS had a stronger effect than RPS. Fecal microbiota analysis showed that RPS and WPS restored intestinal microbiota proportions to normal levels.ConclusionThe results demonstrated that PS and its WPS had a positive effect in relieving oxidative stress in aging mice. WPS outperformed RPS, which might be related to the activation of the Keap1/Nrf2/ARE pathway and regulation of intestinal flora.

Clinical and anthropometric evolution of individuals with cystic fibrosis during COVID-19 pandemic: A 24-month cohort study.

To analyze the evolution of clinical and anthropometric characteristics of children and adolescents with cystic fibrosis (CF) over 24 months, including the period of the COVID-19 pandemic. A longitudinal study with data collection from May 2018 to November 2020 in physical and electronic records from a pediatric reference center, including individuals with CF aged up to 18 years. The sample encompassed 72 individuals. Weight (p < 0.01), height (p < 0.01), and body mass index (BMI) (p = 0.043) were higher in 2020 than in 2018. There were no significant changes in BMI-Z (p = 0.977) and in percentiles of weight (p = 0.540), height (p = 0.458), and BMI percentile (p = 0.454) between both periods. Pancreatic insufficiency was observed in 91.7% of patients in 2020, and there were twice as many confirmed cases of diabetes compared to 2018. There was a 9.7% increase in individuals colonized by the oxacillin-sensitive Staphylococcus aureus (OSSA) (p = 0.039) and an 11.1% reduction in non-colonized individuals (p = 0.008). Although there was an increase in weight, height, and BMI from 2018 to 2020, there were no significant changes in BMI-Z and in percentiles of weight, height, and BMI percentile, suggesting that the anthropometric aspects of nutritional status did not change in this period of 2 years. Moreover, there was an increase in the prevalence of individuals colonized by OSSA and a reduction in the prevalence of individuals non-colonized with any bacteria.

Comparison of Dutch healthy eating and healthy eating indexes and anthropometry in patients with major depression with health subjects: a case-control study

BackgroundDiseases and disorders related to mental health are spreading like other chronic diseases all around the world. Considering the role of food in the prevention and treatment of these disorders, including major depression, investigating the relationship between different food patterns and this disorder is of particular importance. The aim of this study was to compare Dutch healthy eating and healthy eating indexes and anthropometry in patients with major depression with healthy individuals.MethodsIn this case-control study, the final analysis was performed on 67 men and 111 women with an age range of 20–30 years. Height (cm), weight (kg), food frequency questionnaire (FFQ), physical activity (MET-min/week), demographic and PHQ-9 questionnaires were taken from all participants. In the following, all the food ingredients and their components were extracted and used to calculate HEI-2015 and DHD. Statistical analysis was performed using SPSS software with independent t-test, logistic regression and chi-square.ResultsIt was found that people with major depression in this study were mostly women and occupied. The average HEI-2015 in healthy people and those with major depression was 58 and 54.3, respectively. Also, the average DHD in these people was 60.5 and 55, respectively. HEI-2015 and DHD had a significant negative correlation with depression score (r = −0.16, p-value = 0.03) (r = −0.19, p-value = 0.01). Also, in the logistic regression model, before and even after adjusting confounders, HEI-2015 and DHD had a reduced odds ratio in people suffering from major depression. The two groups did not differ significantly in terms of the average factors of height, weight and body mass index (BMI).ConclusionIt seems that HEI2015 and DHD have a significant relationship in reducing major depression. However, due to the small number of studies in this regard, especially in the field of DHD, the need for more studies seems necessary.

Ultra high-frequency ultrasound of fascicles in the ulnar and radial nerves.

Ultra high-frequency ultrasound (UHFUS) has been demonstrated to allow easy visualization and quantification of median and digital nerve fascicles; however, there is a lack of normative data for other upper limb nerves. The purpose of this study was to use UHFUS to establish normative reference values and ranges for fascicle count and density within selected upper extremity nerves. Twenty-one healthy volunteers underwent sonographic examination of the ulnar, superficial branch of the radial, and radial nerves on one upper limb using UHFUS with a 48 MHz linear transducer. The number of fascicles in each peripheral nerve and fascicle density were assessed. The mean fascicle number and fascicle density for each of the measured nerves was ulnar nerve at the wrist 11.7 and 2.0, ulnar nerve at the elbow 9.2 and 1.1, superficial branch of the radial nerve 7.3 and 2.5, and radial nerve at the spiral groove 4.2 and 0.8. A single significant association was observed between CSA and fascicle number in the ulnar nerve at the wrist (p = .023, r = 0.66). Neither fascicle number nor density could be predicted by age, sex, height, weight, or body mass index. UHFUS may help to establish a baseline of normative data on upper limb nerves that are not frequently biopsied due to their mixed motor and sensory functions and has the potential for increased understanding of nerve fascicular anatomy to improve diagnostic accuracy of focal nerve lesions, particularly those with selective fascicular involvement.

Changes in Cephalic Index and Head circumference of Igbo Children and Adolescents in a Nigerian Population

Background: The cephalic index and head circumference are important anthropometric parameters that can provide insights into the physical characteristics and growth patterns of populations. There is dearth of data on Cephalic Index and Head circumference of Igbo Children and Adolescents. Method: This study examined 725 Igbo children and adolescents aged 5 to 19 years in Enugu, South-eastern Nigeria, using a cross-sectional approach. Results: The majority of participants exhibited mesocephalic head shape (43.2%), with brachycephalic and dolichocephalic shapes observed in 32.7% and 14.2% of the population, respectively. Mean head circumference increased with age in both sexes. Cephalic indices in boys under 12 and girls under 15 were below 80 but increased above these ages. Changes in head shape, potentially towards brachycephalization, were noted as children grew. Significant correlations were found between head circumference and cephalic index with age, height, weight, and body mass index, suggesting their relevance in forensic and anthropological investigations. Conclusion: Our results indicate diversity in head shapes and sizes, with mesocephalic heads being most common. As age increases, head circumference also tends to increase, and changes in head shape towards brachycephalization was observed. These findings underscore the importance of understanding anthropometric variations in different populations and suggest avenues for further research, particularly longitudinal studies, to explore the factors influencing these patterns.

Subchronic co-exposure of polystyrene nanoplastics and 3-BHA significantly aggravated the reproductive toxicity of ovaries and uterus in female mice

Both nanoplastics (NPs) and 3-tert-butyl-4-hydroxyanisole (3-BHA) are environmental contaminants that can bio-accumulate through the food chain. However, the combined effects of which on mammalian female reproductive system remain unclear. Here, the female ICR-CD1 mice were used to evaluate the damage effects of ovaries and uterus after NPs and 3-BHA co-treatment for 35 days. Firstly, co-exposure significantly reduced the body weight and organ index of ovaries and uterus in mice. Secondly, combined effects of NPs and 3-BHA exacerbated the histopathological abnormalities to the ovaries and uterus and decreased female sex hormones such as FSH and LH while increased antioxidant activities including CAT and GSH-Px. Moreover, the apoptotic genes, inflammatory cytokines and the key reproductive development genes such as FSTL1 were significantly up-regulated under co-exposure conditions. Thirdly, through transcriptional and bioinformatics analysis, immunofluorescence and western blotting assays, together with molecular docking simulation, we determined that co-exposure up-regulated the FSTL1, TGF-β and p-Smad1/5/9 but down-regulated the expression of BMP4. Finally, the pharmacological rescue experiments further demonstrated that co-exposure of NPs and 3-BHA mainly exacerbated the female reproductive toxicity through FSTL1-mediated BMP4/TGF-β/SMAD signaling pathway. Taken together, our studies provided the theoretical basis of new environmental pollutants on the reproductive health in female mammals.

Capsaicin reduces blood glucose and prevents prostate growth by regulating androgen, RAGE/IGF-1/Akt, TGF-β/Smad signalling pathway and reversing epithelial-mesenchymal transition in streptozotocin-induced diabetic mice.

Type 2 diabetes mellitus (T2DM) is a metabolic disease. Diabetes increases the risk of benign prostatic hyperplasia (BPH). Capsaicin is extracted from chili peppers and possesses many pharmacological properties, including anti-diabetic, pain-relieving, and anti-cancer properties. This study aimed to investigate the effects of capsaicin on glucose metabolism and prostate growth in T2DM mice and uncover the related mechanisms. Mice model of diabetes was established by administering a high-fat diet and streptozotocin. Oral administration of capsaicin for 2weeks inhibited prostate growth in testosterone propionate (TP)-treated mice. Furthermore, oral administration of capsaicin (5mg/kg) for 2weeks decreased fasting blood glucose, prostate weight, and prostate index in diabetic and TP-DM mice. Histopathological alterations were measured using hematoxylin & eosin (H&E) staining. The protein expression of 5α-reductase type II, androgen receptor (AR), and prostate-specific antigen (PSA) were upregulated in diabetic and TP-DM mice, but capsaicin reversed these effects. Capsaicin decreased the protein expression of p-AKT, insulin-like growth factor-1 (IGF-1), IGF-1R, and the receptor for advanced glycation end products (RAGE) in diabetic and TP-DM mice. Capsaicin also regulated epithelial-mesenchymal transition (EMT) and modulated the expression of fibrosis-related proteins, including E-cadherin, N-cadherin, vimentin, fibronectin, α-SMA, TGFBR2, TGF-β1, and p-Smad in TP-DM mice. In this study, capsaicin alleviated diabetic prostate growth by attenuating EMT. Mechanistically, capsaicin affected EMT by regulating RAGE/IGF-1/AKT, AR, and TGF-β/Smad signalling pathways. These results provide with new therapeutic approach for treating T2DM or T2DM-induced prostate growth.

Abstract PO1-03-10: Differential microbial metabolic pathways associated with resistance to neoadjuvant immunotherapy in locally advanced triple negative breast cancer

Abstract Differential microbial metabolic pathways associated with resistance to neoadjuvant immunotherapy in locally advanced triple negative breast cancer Background: It has previously been shown that microbial metabolic pathways are differentially activated in immunotherapy resistance, hence can serve as potential targets for therapeutic intervention. With the advent of Immune Checkpoint Blockers in the neoadjuvant setting of locally advanced (LA) TNBC, we hypothesized that similar microbial metabolite mediated resistance may be at play. We are presenting the real world data for neoadjuvant treatment in early TNBC along with a subset of tumor metabolite analysis. Method: 35 patients who received neoadjuvant pembrolizumab and chemotherapy for LA TNBC were identified at Moffitt Cancer Center between July 2019 to January 2023. These included 22 Caucasian, 5 African American, 2 Hispanic and 6 patients with undisclosed race. The age range was 33-78 years. The weight and Body Mass Index range was 55.3 kg-127.3 kg and 20.96-45.43 kg/m2 respectively. Nine patients had stage III disease while 24 had stage II breast cancer. The response was assessed in 33 patients; 20 patients (60.6%) achieved pathological complete response (pCR) and 13 (39.4%) had residual disease (RD). 1 patient developed severe immune mediated toxicity with colitis, hepatitis, myasthenia gravis leading to death while 1 patient had disease progression leading to drug discontinuation. Six patients developed immune mediated adverse events. We conducted untargeted metabolomic profiling on 24 patients to identify differentially abundant metabolites associated with pCR (ypT0/is ypN0) vs RD; 16 vs 8 patients respectively. Formalin fixed paraffin embedded (FFPE) slides from tumor tissue vs tumor bed were retrieved and histopathological evaluation of tumor cells was performed. 20 μm sections of FFPE block were used for untargeted metabolomics via liquid chromatography/mass spectrometry. Among the 200 metabolites detected, 63 were differentially abundant between pCR and tumor samples with RD. After correcting for false discovery rate, we observed striking differential activation of two microbial metabolic pathways. Samples with RD had significantly elevated kynurenine (OR-3.64 X1034, P-1.94 X 10-74 and kynurenine/Tryptophan ratio). The tryptophan, kynurenine pathway has been known to be overexpressed in patients resistant to immunotherapy and modulated by the microbiome. Similarly, the purine metabolic pathway, specifically microbiota-derived immunostimulatory metabolites- inosine, hypoxanthine, uric acid were significantly depleted in patients with RD (Inosine OR-0.54, p-0.007, Hypoxanthine OR-0.5, p-0.00039, uric acid OR: 0.41, P-0.003). Previously Inosine has been shown to increase the anti-tumor effects of immune checkpoint blockade by enhancing CD8+ effector T-cell function. Hence depletion of inosine, hypoxanthine and uric acid signals lack of an effector CD8 T cell response. Conclusion: Despite being a small study, it corroborates pCR rates noted in KEYNOTE 522 in the real world setting but shows significant concern for serious immune mediated adverse effects. This highlights the importance of stratifying patients who might be resistant to ICB or develop significant toxicities, thus deriving little to no benefit from standard neoadjuvant treatment. This underscores the need to develop precision-based treatment algorithms. The study represents one of the first investigations of differential abundance of microbial metabolites with immunotherapy resistance in LA TNBC. Our results highlight two microbially mediated mechanisms that could be targeted to improve pCR rates in LA TNBC. We are working to identify microbial metabolic pathways associated with immune mediated toxicity. Citation Format: Humaira Sarfraz, Brian Czerniecki, Zena Jameel, Michael Jaglal, Mostafa Eysha, Turkan Ozkul, Jameel Muzaffar, Aditi Saha, Sara Sarfraz, Fatima Zahra, Min Liu, Khushali Jhaveri, Melissa Sur, Adrianna Bagos-Estevez, Shahla Bari. Differential microbial metabolic pathways associated with resistance to neoadjuvant immunotherapy in locally advanced triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-03-10.

Tectorigenin inhibits inflammatory responses in murineinflammatory bowel disease and LPS-stimulated macrophages via inactivating MAPK signaling pathway.

Considering the antihepatitis effects of Tectorigenin (TEC), and the same adenosine mitogen-activated protein kinase (MAPK) pathway in both hepatitis and inflammatory bowel disease (IBD) models, exploring the role of TEC in IBD is contributive to develop a new treatment strategy against IBD. The IBD mouse model was constructed by feeding with dextran sodium sulfate (DSS) and injection of TEC. Afterward, the mouse body weight, colon length, and disease activity index (DAI) were tested to assess the enteritis level. Mouse intestine lesions were detected by hematoxylin and eosin staining. Murine macrophages underwent lipopolysaccharide (LPS) induction to establish an inflammation model. Cell viability was determined by cell counting kit-8 assay. Enzyme-linked immunosorbent assay was performed to measure interleukin 6(IL-6) and tumor necrosis factor-α (TNF-α) levels. Cyclooxygenase-2(COX-2) and inducible nitric oxide synthase(iNOS) expressions were quantified via quantitative reverse transcription polymerase chain reaction. Levels of MAPK pathway-related proteins (p-P38, P38, p-Jun N-terminal kinase(JNK), JNK, signal-regulated kinase(ERK), p-ERK), COX-2 and iNOS were quantitated by Western blot. TEC improved the inflammatory response through ameliorating weight loss, shortening colon, and increasing DAI score in IBD mouse. Expressions of intestinal inflammatory factors (IL-6, TNF-α, iNOS and COX-2) and MAPK pathway-related proteins (p-P38, p-JNK, and p-ERK) were increased both in DSS-induced mouse intestinal tissue, but TEC inhibited expressions of inflammatory factors. The same increased trend was identified in LPS-induced macrophages, but TEC improved macrophage inflammation, as evidenced by downregulation of inflammatory factors. TEC mitigates IBD and LPS-induced macrophage inflammation in mice via inhibiting MAPK signaling pathway.

Risk of Cephalic Vein Injury During the Creation of an Anterior Portal in Shoulder Arthroscopy.

There is a risk of cephalic vein injury during shoulder arthroscopy. However, limited data regarding its anatomic course are available. To analyze the positional relationship and factors affecting the distance between the coracoid tip and cephalic veins. Case series; Level of evidence, 4. A total of 80 contrast-enhanced computed tomography images from 80 patients (mean age, 49.6 ± 20.3 years; 61 men) were retrospectively analyzed. The distance between the center of the coracoid tip and the vertical line through the cephalic vein was measured in the axial (D1) and sagittal (D2) planes. The distance between 1 cm lateral to the center of the coracoid tip and the vertical line through the cephalic vein was measured in the sagittal plane (D3). Each distance was compared according to patient sex and laterality. Associations between each distance and the patient's age, height, weight, and body mass index were investigated. The mean D1 was 18.4 ± 7.3 mm in 59 patients. The mean D2 was 23.4 ± 11.6 mm, and it was within 10 mm in 10 patients (12.5%). The mean D3 was 33.7 ± 12.2 mm. There was no significant difference in D1, D2, and D3 according to patient sex or laterality. A positive correlation was observed only between D3 and patient height (r = 0.320; P = .034). The cephalic vein was found to travel a mean of 23.4 mm distal and 33.7 mm distal to 1 cm lateral to the coracoid tip. Therefore, Care should be taken to avoid cephalic vein injury when creating an anterior inferior portal or 5-o'clock portal around these areas.

Cord Blood Proteomic Profiles, Birth Weight, and Early Life Growth Trajectories.

The cord blood proteome, a repository of proteins derived from both mother and fetus, might offer valuable insights into the physiological and pathological state of the fetus. However, its association with birth weight and growth trajectories early in life remains unexplored. To identify cord blood proteins associated with birth weight and the birth weight ratio (BWR) and to evaluate the associations of these cord blood proteins with early growth trajectories. This cohort study included 288 mother-child pairs from the ongoing prospective Environmental Influence on Early Aging birth cohort study. Newborns were recruited from East-Limburg Hospital in Genk, Belgium, between February 2010 and November 2017 and followed up until ages 4 to 6 years. Data were analyzed from February 2022 to September 2023. The outcome of interest was the associations of 368 inflammatory-related cord blood proteins with birth weight or BWR and with early life growth trajectories (ie, rapid growth at age 12 months and weight, body mass index [BMI] z score, waist circumference, and overweight at age 4-6 years) using multiple linear regression models. The BWR was calculated by dividing the birth weight by the median birth weight of the population-specific reference growth curve, considering parity, sex, and gestational age. Results are presented as estimates or odds ratios (ORs) for each doubling in proteins. The sample included 288 infants (125 [43.4%] male; mean [SD] gestation age, 277.2 [11.6] days). The mean (SD) age of the child at the follow-up examination was 4.6 (0.4) years old. After multiple testing correction, there were significant associations of birth weight and BWR with 7 proteins: 2 positive associations: afamin (birth weight: coefficient, 341.16 [95% CI, 192.76 to 489.50]) and secreted frizzled-related protein 4 (SFRP4; birth weight: coefficient, 242.60 [95% CI, 142.77 to 342.43]; BWR: coefficient, 0.07 [95% CI, 0.04 to 0.10]) and 5 negative associations: cadherin EGF LAG 7-pass G-type receptor 2 (CELSR2; birth weight: coefficient, -237.52 [95% CI, -343.15 to -131.89]), ephrin type-A receptor 4 (EPHA4; birth weight: coefficient, -342.78 [95% CI, -463.10 to -222.47]; BWR: coefficient, -0.11 [95% CI, -0.14 to -0.07]), SLIT and NTRK-like protein 1 (SLITRK1; birth weight: coefficient, -366.32 [95% CI, -476.66 to -255.97]; BWR: coefficient, -0.11 [95% CI, -0.15 to -0.08]), transcobalamin-1 (TCN1; birth weight: coefficient, -208.75 [95% CI, -305.23 to -112.26]), and unc-5 netrin receptor D (UNC5D; birth weight: coefficient, -209.27 [95% CI, -295.14 to -123.40]; BWR: coefficient, -0.07 [95% CI, -0.09 to -0.04]). Further evaluation showed that 2 proteins were still associated with rapid growth at age 12 months (afamin: OR, 0.32 [95% CI, 0.11-0.88]; TCN1: OR, 2.44 [95% CI, 1.26-4.80]). At age 4 to 6 years, CELSR2, EPHA4, SLITRK1, and UNC5D were negatively associated with weight (coefficients, -1.33 to -0.68 kg) and body mass index z score (coefficients, -0.41 to -0.23), and EPHA4, SLITRK1, and UNC5D were negatively associated with waist circumference (coefficients, -1.98 to -0.87 cm). At ages 4 to 6 years, afamin (OR, 0.19 [95% CI, 0.05-0.70]) and SLITRK1 (OR, 0.32 [95% CI, 0.10-0.99]) were associated with lower odds for overweight. This cohort study found 7 cord blood proteins associated with birth weight and growth trajectories early in life. Overall, these findings suggest that stressors that could affect the cord blood proteome during pregnancy might have long-lasting associations with weight and body anthropometrics.

Lycium barbarum polysaccharide remodels colon inflammatory microenvironment and improves gut health

AimDisturbed intestinal microbiota has been implicated in the inflammatory microenvironment of the colon, which usually results in ulcerative colitis (UC). Given the limitations of these drugs, it is important to explore alternative means of protecting the gut health from UC. This study aimed to investigate the potential of polysaccharides as beneficial nutrients in the regulation of the gut microbiota, which determines the inflammatory microenvironment of the colon. Materials and methodsMice were treated with dextran sulfate sodium (DSS) to evaluate the effects and mechanisms of Lycium barbarum polysaccharide (LBP) in remodeling the inflammatory microenvironment and improving gut health. Body weight and disease activity indices were monitored daily. Hematoxylin and eosin staining was used to analyze colon dynamics. The levels of inflammatory indicators and expression of MUC-2, claudin-1, ZO-1, and G-protein-coupled receptor 5 (TGR5) were determined using assay kits and immunohistochemistry, respectively. 16S rRNA high-throughput sequencing of the intestinal microbiota and liquid chromatography-tandem mass spectrometry for related bile acids were used. ResultsLBP significantly improved the colonic tissue structure by upregulating MUC-2, claudin-1, and ZO-1 protein expression. The bacterial genus Dubosiella was dominant in healthy mice, but significantly decreased in mice treated with DSS. LBP rehabilitated Dubosiella in the sick guts of DSS mice to a level close to that of healthy mice. The levels of other beneficial bacterial genera Akkermansia and Bifidobacterium were also increased, whereas those of the harmful bacterial genera Turicibacter, Clostridium_sensu_stricto_1, Escherichia-Shigella, and Faecalibaculum decreased. The activity of beneficial bacteria promoted the bile acids lithocholic and deoxycholic acids in mice with UC, which improved the gut barrier function through the upregulation of TGR5. ConclusionThe inflammatory microenvironment in the gut is determined by the balance of the gut microbiota. LBP showed great potential as a beneficial nutrient for rehabilitating Dubosiella which is dominant in the gut of healthy mice. Nutrient-related LBP may play an important role in gut health management.

The Association between Dietary Acid Load and Non-Communicable Diseases: A Cohort Study in Shahrekord

Background and aim: It has recently been suggested that acid-base imbalances may play a role in some types of cardiovascular diseases and metabolic disorders. The aim of this study is to investigate the association between dietary acid load and common non-communicable diseases (NCDs). Methods: In this cross-sectional study, 1800 participants were enrolled in a cohort study in Shahrekord. Data were collected using a Food Frequency Questionnaire (FFQ). The potential renal acid load (PRAL) was calculated using the intestinal absorption of five nutrients including protein, potassium, phosphorus, magnesium, and calcium. The association of dietary acid load with NCDs was investigated in two models. Then, the raw model was adjusted by including calorie intake and age; after adjusting the effect of the two variables, the association between dietary acid load and the studied NCDs was not statistically significant. Results: The mean age of the participants was 51.49±9.27 years, and 941 (52.27%) of them were female. Mean±SD acid load score was -6.88±23.23. The results showed that there was a significant association between dietary acid load and age (P=0.005), weight (P=0.0001), waist circumference (P=0.016), hip circumference (P=0.0001), waist-to-hip ratio (P=0.01), body mass index (P=0.004), and triglyceride (P=0.012). In the raw model, a significant association was observed between dietary acid load and hypertension (OR=0.57, 0.39-0.8). Conclusion: In this study, no significant association was observed between dietary acid load and NCDs, but the variable was associated with weight and body mass index as the most important risk factors for NCDs.