Healthy Counterparts Research Articles

Current and future research on the association between gut microbiota and breast cancer.

Breast cancer (BC) is a prevalent malignancy. There exists a strong association between gut microbiota (GM) and the development of BC. The GM composition in individuals with BC significantly differs from that in their healthy counterparts. Furthermore, the distribution of GM varies significantly among individuals with different types of BC. The GM can impact BC through metabolite secretion, the gut-mammary axis, and other pathways. Modulating the GM can serve as a very promising potential therapeutic strategy in the treatment of BC. This article will summarize existing research, focusing on the relationship between intestinal microbiota and BC. At the same time, the project will also analyze the application value of intestinal microorganisms in BC intervention work, so as to provide a reference for the further development of BC prevention and treatment work.

Frontal plane pelvic kinematics during high velocity running: Association with hamstring injury history

IntroductionHamstring injuries are the most prevalent non-contact soft tissue injury in sports, with a larger portion of injuries being recurrent. The sagittal plane running kinematics correlated to hamstring injury history has been well documented. However, analysis of frontal plane kinematics allows for observation of stability and symmetry. This study aimed to examine the frontal plane running kinematics of elite collegiate level sprinters, with and without previous hamstring injury, compared to healthy counterparts. MethodsThirty-nine participants performed three 50-m sprints, with three inertial measurement unit sensors placed on the pelvis: one on each iliac crest and one on the sacrum. Participants were classified based on sex, competitive status, and injury history. To investigate differences based on group classification, the data were used to analyze mediolateral motion (relative magnitude of mediolateral acceleration) and asymmetry (difference in acceleration between right and left iliac crests) during each stance phase throughout the run. ResultsInjured sprinters displayed significantly greater mediolateral motion and asymmetry during stances than healthy counterparts. ConclusionsThis study demonstrates that frontal plane running stance dynamics are different in athletes with previous hamstring injury than healthy athletes. These athletes may benefit from rehabilitation strategies targeting postural control and stability during dynamic tasks.

Morphological characterisation of pediatric Turner syndrome aortae: Insights from a small cohort study.

Cardiovascular disease is widespread in girls and women living with Turner syndrome (TS). Despite this prevalence, cardiovascular risk evaluation using the current guidelines has seen life-threatening aortic events occurring at dimensions classified within the normal threshold. In this study, we characterized the three-dimensional aortic geometries of Turner syndrome children and their age-matched healthy counterparts to evaluate various morphological parameters. Turner syndrome girls had overall greater values in ten out of fifteen parameters examined (p>0.05), when compared to healthy children: the aortic arch height and width; the ascending aorta, aortic arch (2 locations), and descending aorta diameters; the ratio of the ascending to descending aorta diameter; average curvature; average torsion; and average curvature-torsion score. Additionally, significant associations were found in the TS group: body surface area and both arch height (p=0.03) and arch height to width ratio (p=0.05), and aortic arch diameter and both body surface area (p=0.04) and weight (p=0.04). The new information resulting from this small cohort study contributes to an improved understanding of the morphological parameters affecting the hemodynamic environment in TS, and the clinical assessment of the increased cardiovascular risk in this population.

AGEs and RAGE: metabolic and molecular signatures of the glycation-inflammation axis in malignant or metastatic cancers.

From attributing mutations to cancers with the advent of cutting-edge genetic technology in recent decades, to re-searching the age-old theory of intrinsic metabolic shift of cancers (Warburg's glycolysis), the quest for a precise panacea for mainly the metastatic cancers, remains incessant. This review delineates the advanced glycation end product (AGE)-receptor for AGE (RAGE) pathway driven intricate oncogenic cues, budding from the metabolic (glycolytic) reliance of tumour cells, branching into metastatic emergence of malignancies. Strong AGE-RAGE concomitance in metastasis, chemo-resistance and cancer resurgence adversely incite disease progression and patient mortality. At the conjunction of metabolic and metastatic shift of cancers, are the "glycolytically" generated AGEs and AGE-activated RAGE, instigating aberrant molecular pathways, culminating in aggressive malignancies. AGEs as by-products of metabolic insurgence, modify the metabolome, epigenome and microbiome, besides coercing the inter-, intra- and extra-cellular micro-milieu conducive for oncogenic events like epithelial-mesenchymal transition (EMT). AGE-RAGE synergistically elicit ATP surge for surplus energy, autophagy for apoptotic evasion and chemo-resistance, insulin-like growth factor 1 (IGF-1) for meta-inflammation and angiogenesis, high mobility group box-1 (HMGB1) for immune tolerance, S100 proteins for metastasis, and p53 protein attenuation for tumour suppression. AGEs are pronouncedly reported in invasive forms of breast, prostate, colon and pancreatic cancers, higher in patients with cancer than healthy counterparts, and higher in advanced stage than localized phase. Hence, the investigation of person-specific presence of AGEs, soluble RAGE and AGE-activated RAGE can be advocated as impending bio-markers for diagnostic, prognostic and therapeutic purposes, to predict cancer risk in patients with diabetes, obesity, metabolic syndrome as well as general population, to monitor prognosis and metastasis in patients with cancer, and to reckon complications in cancer survivors. Furthermore, clinical reports of exogenous (dietary) and endogenous (internally formed) AGEs in cancer patients, and contemporary clinical trials involving AGE-RAGE axis in cancer are underlined with theranostic implications.

Pre- and post-treatment evaluation of routine blood analysis in patients with attention deficit hyperactivity disorder and comparison with the healthy control group

This study aimed to examine potential disparities in hematologic inflammation parameters between children diagnosed with attention deficit hyperactivity disorder (ADHD) and their healthy counterparts and to determine whether atomoxetine treatment induced any alterations in inflammation indicators. This case–control study involved 43 children aged 6–13 years, 22 diagnosed with ADHD for the first time, and 21 healthy children. In all children, complete blood count and albumin, C-reactive protein (CRP), thyroid stimulating hormone (TSH), free thyroxine (free T4), folate, vitamin B12, aspartate aminotransferase (AST), alanine transaminase (ALT), creatinine and urea values were performed. Children with ADHD were started on atomoxetine treatment, and one month later, the blood test was repeated for those who commenced treatment. Neutrophil (p = 0.005), platelet (PLT) (p = 0.002), neutrophil/lymphocyte ratio (NLR) (p = 0.001), platelet/lymphocyte ratio (PLR) (p < 0.001), systemic immune /inflammation index (SII) (p < 0.001) and pan-immune-inflammation value (PIV) (p = 0.025) parameters were found to be significantly higher than the control group, while the lymphocyte value (p = 0.001) was found to be significantly lower. In those in the ADHD group, lymphocyte (p = 0.041) and albumin (p = 0.027) values increased significantly after treatment. The results of this study show the increase in inflammation in drug-naive ADHD patients and the partial improvement after treatment. However, there is a need to evaluate inflammation in larger samples after longer-term treatments and follow-ups.

Phenotypic Classification and Clinical Examination of Anemia in Iraqi Water Buffalo in Nasiriyah Governorate

This research aims to classify anemia cases in the Iraqi water buffalo population by collecting 140 blood samples from buffaloes in Nasiriyah Governorate pastures. These samples were collected randomly from three age groups: &gt; 1 year, 1-4 years, and &lt; 5 years. Blood sample analysis revealed 45 anemia cases (32.12%) and 95 healthy cases (67.88%). Phenotypic classification of anemia encompassed microcytic hypochromic (12.14%), macrocytic hypochromic (7.85%), normocytic hypochromic (6.42%), and normocytic normochromic (5.71%) cases. Erythrocyte sedimentation rate (ESR) notably increased in anemic buffaloes, displaying a statistically significant disparity (P&lt; 0.05) compared to healthy counterparts. Anemia cases exhibited higher neutrophil counts in white blood cell relative differentials. For the three age groups, hemoglobin (Hb), packed blood cell volume (PCV), and total red blood cell count (RBC) values indicated significant decreases from normal levels, showcasing statistical significance (P&lt; 0.05) between healthy and anemic buffaloes. While anemia cases generally displayed normal iron concentrations, microcytic anemia demonstrated lower iron levels in the 1-4 and &gt;5 years age groups, with iron levels reaching the minimum global normal range in the &lt;1 year age group. Copper concentrations remained normal in all healthy cases and anemia cases, except for microcytic anemia, which showed reduced levels across age groups.&#x0D; In conclusion, this study comprehensively characterizes anemia in Iraqi water buffaloes through clinical, hematological, and elemental analyses. The findings underscore the prevalence of various anemia types, their age-related variations, and significant hematological deviations in anemic buffaloes compared to healthy counterparts. This research enhances our understanding of anemias' impact on this population and provides valuable insights for future diagnostic and management strategies.

The effect of different prebiotics on intestinal probiotics in newly diagnosed diabetic patients.

Prebiotics exert favorable effects on the host through interactions with probiotics, and their beneficial impacts have been extensively validated across various chronic ailments, including diabetes. This study presents findings from a case-control investigation involving 10 individuals with type 2 diabetes mellitus (T2DM) and 10 healthy counterparts. Fresh stool specimens were collected from all participants. Following a 24-h fermentation period in mediums containing xylitol and mannitol, the observed increase in Lactobacillus abundance within the case group exceeded that of the control group. Similarly, in mediums containing soluble starch, choline, and L-carnitine, the augmentation of Bifidobacterium within the case group surpassed that of the controls. Notably, a statistically significant divergence in sugar degradation rate emerged between the case and control groups, specifically in the medium harboring lactulose and isomalto-oligosaccharides. Remarkably, the degradation rate of lactulose exhibited a positive correlation with the expansion of Bifidobacterium (R 2 = .147, p = .037). Likewise, the degradation rate of isomalto-oligosaccharides demonstrated a positive correlation with Bifidobacterium proliferation (R 2 = .165, p = .041). In conclusion, prebiotics like xylitol and mannitol exhibit the capacity to enhance intestinal probiotic populations in individuals newly diagnosed with diabetes. The modifications in the intestinal flora homeostasis of diabetic patients may be evidenced by alterations in the degradation rate of specific prebiotic substrates.

High resting energy expenditure, less fat-free mass, and less muscle strength in HIV-infected children: a matched, cross-sectional study.

Many improvements have been made in the treatment of human immunodeficiency virus (HIV) in pediatric patients; however, challenges remain in terms of achieving normal growth, body composition, and metabolism during treatment, etc. Current nutritional recommendations are based on studies performed in adults, with limited data on the HIV-infected pediatric population. Therefore, this study aimed to compare the resting energy expenditure (REE) of asymptomatic HIV-infected pediatric patients with healthy counterparts and to compare body composition, dietary intake, and physical activity between the two groups. This was a cross-sectional study of asymptomatic HIV-infected children who were receiving antiretroviral therapy; the infected group was compared with the uninfected group, matched by age (± 6 months), sex, and body mass index (± 0.5 z-score). Participants were recruited between 2021 and 2022, as outpatients. In both groups, REE was determined by indirect calorimetry and body composition by bioelectrical impedance analysis and hand strength, measured using a hydraulic hand dynamometer. Seventy-eight participants were enrolled, where n = 39 HIV-infected children and n = 39 controls, with a mean age of 11.6 ± 3.4 years old. REE was significantly higher in the HIV group (1254.4 ± 334.7 kcal/day vs. 1124.7 ± 321 kcal/day, p = 0.013) than in the control group. Fat-free mass (FFM) was lower in the HIV group (28.2 ± 10.5 kg vs. 32 ± 11.2 kg, p = 0.001); this trend continued when the index skeletal muscle was evaluated (7.2 ± 1.2 vs. 7.6 ± 1.5, p = 0.04). The strength of the dominant hand was also lower in the HIV group (12 (8-18) kg vs. 20 (10.5-26) kg, p < 0.0001). Children with asymptomatic HIV infection have higher REE than their uninfected peers. They also present decreased FFM, skeletal muscle mass index, and muscle strength. These parameters should be considered during nutritional assessment in this population to have a favorable impact on nutritional status and growth.

An exploratory study of cell stiffness as a mechanical label-free biomarker across multiple musculoskeletal sarcoma cells

BackgroundCancer cells are characterized by changes in cell cytoskeletal architecture and stiffness. Despite advances in understanding the molecular mechanisms of musculoskeletal cancers, the corresponding cellular mechanical properties remain largely unexplored. The aim of this study was to investigate the changes in cellular stiffness and the associated cytoskeleton configuration alterations in various musculoskeletal cancer cells.MethodsCell lines from five main sarcoma types of the musculoskeletal system (chondrosarcoma, osteosarcoma, Ewing sarcoma, fibrosarcoma and rhabdomyosarcoma) as well as their healthy cell counterparts (chondrocytes, osteoblasts, mesenchymal stem cells, fibroblasts, skeletal muscle cells) were subjected to cell stiffness measurements via atomic force microscopy (AFM). Biochemical and structural changes of the cytoskeleton (F-actin, β-tubulin and actin-related protein 2/3) were assessed by means of fluorescence labelling, ELISA and qPCR.ResultsWhile AFM stiffness measurements showed that the majority of cancer cells (osteosarcoma, Ewing sarcoma, fibrosarcoma and rhabdomyosarcoma) were significantly less stiff than their corresponding non-malignant counterparts (p < 0.001), the chondrosarcoma cells were significant stiffer than the chondrocytes (p < 0.001). Microscopically, the distribution of F-actin differed between malignant entities and healthy counterparts: the organisation in well aligned stress fibers was disrupted in cancer cell lines and the proteins was mainly concentrated at the periphery of the cell, whereas β-tubulin had a predominantly perinuclear localization. While the F-actin content was lower in cancer cells, particularly Ewing sarcoma (p = 0.018) and Fibrosarcoma (p = 0.023), this effect was even more pronounced in the case of β-tubulin for all cancer-healthy cell duos. Interestingly, chondrosarcoma cells were characterized by a significant upregulation of β-tubulin gene expression (p = 0.005) and protein amount (p = 0.032).ConclusionModifications in cellular stiffness, along with structural and compositional cytoskeleton rearrangement, constitute typical features of sarcomas cells, when compared to their healthy counterpart. Notably, whereas a decrease in stiffness is typically a feature of malignant entities, chondrosarcoma cells were stiffer than chondrocytes, with chondrosarcoma cells exhibiting a significantly upregulated β-tubulin expression. Each Sarcoma entity may have his own cellular-stiffness and cytoskeleton organisation/composition fingerprint, which in turn may be exploited for diagnostic or therapeutic purposes.

The Abnormal Accumulation of Lipopolysaccharide Secreted by Enriched Gram-Negative Bacteria Increases the Risk of Rotavirus Colonization in Young Adults.

Human rotavirus (HRV) is an enteric virus that causes infantile diarrhea. However, the risk factors contributing to HRV colonization in young adults have not been thoroughly investigated. Here, we compared the differences in dietary habits and composition of gut microbiota between asymptomatic HRV-infected young adults and their healthy counterparts and investigated potential risk factors contributing to HRV colonization. Our results indicated that asymptomatic HRV-infected adults had an excessive intake of milk and dairy and high levels of veterinary antibiotics (VAs) and preferred veterinary antibiotic (PVAs) residues in urine samples. Their gut microbiota is characterized by abundant Gram-negative (G-) bacteria and high concentrations of lipopolysaccharide (LPS). Several opportunistic pathogens provide discriminatory power to asymptomatic, HRV-infected adults. Finally, we observed an association between HRV colonization and disrupted gut microbiota caused by the exposure to VAs and PVAs. Our study reveals the traits of disrupted gut microbiota in asymptomatic HRV-infected adults and provides a potential avenue for gut microbiota-based prevention strategies for HRV colonization.

Assessment of Healthy Eating Index and Serum Levels of 25-hydroxyvitamin D and Zinc in Prostate Cancer Patients

Background and Objectives Prostate cancer is the most common malignant cancer in men. In this study, the healthy eating index (HEI) and serum levels of 25-hydroxyvitamin D and zinc were evaluated in prostate cancer patients compared with healthy individuals. Subjects and Methods In this study, 30 men who had recently been diagnosed with prostate cancer were compared with 30 otherwise healthy age-matched men in terms of their serum levels of 25 hydroxyvitamin D and zinc as well as HEI. The latter was evaluated in both groups using a 3-day food record. Results There was no significant difference between the two groups in terms of age, weight, BMI and waist circumference. The scores of all components of HEI were not significantly different in the two groups, and in spite of the lower total HEI score in the prostate cancer group, this difference was not statistically significant. Differences between the two groups in terms of serum zinc levels were marginally significant (P-value=0.053). However, the serum level of 25-hydroxyvitamin D in the prostate cancer group was significantly lower than that in the control group (P-value =0.046). Conclusion The results of this study showed that there are statistically significant and marginally significant differences between prostate cancer patients and their otherwise healthy aged-matched counterparts in terms of serum levels 25 hydroxyvitamin D and zinc, respectively. There was no significant difference between the two groups regarding the HEI score.

Hyodeoxycholic acid ameliorates nonalcoholic fatty liver disease by inhibiting RAN-mediated PPARα nucleus-cytoplasm shuttling

Nonalcoholic fatty liver disease (NAFLD) is usually characterized with disrupted bile acid (BA) homeostasis. However, the exact role of certain BA in NAFLD is poorly understood. Here we show levels of serum hyodeoxycholic acid (HDCA) decrease in both NAFLD patients and mice, as well as in liver and intestinal contents of NAFLD mice compared to their healthy counterparts. Serum HDCA is also inversely correlated with NAFLD severity. Dietary HDCA supplementation ameliorates diet-induced NAFLD in male wild type mice by activating fatty acid oxidation in hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent way because the anti-NAFLD effect of HDCA is abolished in hepatocyte-specific Pparα knockout mice. Mechanistically, HDCA facilitates nuclear localization of PPARα by directly interacting with RAN protein. This interaction disrupts the formation of RAN/CRM1/PPARα nucleus-cytoplasm shuttling heterotrimer. Our results demonstrate the therapeutic potential of HDCA for NAFLD and provide new insights of BAs on regulating fatty acid metabolism.

Three-Dimensional (3D) Morphometric Analysis of Plegic and Healthy Feet of Patients with Stroke

Objective: This study aimed to quantitatively assess the changes in foot morphology in stroke patients using 3D scanning and focused on parameters like foot volume, area, and the root mean square difference (RMS) values. The objective was to enhance our understanding of post-stroke foot morphology and its potential relevance for rehabilitation, especially in designing orthotic supports and specialized footwear for stroke patients. Methods: Our study involved fourteen right hemiplegia patients and twenty healthy subjects. Stroke patients were assessed using international scales. We utilized a 3D scanning device to digitize and examine the differences in foot morphology between hemiplegic and healthy subjects, analyzing the data on a computer platform. Results: In the context of post-stroke individuals with hemiplegic feet, our morphometric analysis revealed notable differences in foot area and foot volume when compared to their healthy counterparts. These distinctions extended to linear measurements encompassing foot length, foot width, instep height, bimalleolar width, and ball width. Significantly, RMS exhibited a substantial increase in the patient cohort compared to the healthy group (p&lt;0.05). Our investigation also established correlations between these standing morphometric parameters and RMS alterations, with noteworthy coefficients for various parameters: RMS(Foot Length Difference, 0.41), RMS(Foot Width Difference, 0.45), RMS(Instep Height Difference, 0.58), RMS(Ball Width Difference, 0.58), RMS(Bimalleolar Width Difference, 0.19), RMS(Volume Difference, 0.74), and RMS(Area Difference, 0.62). Conclusion: This study suggests incorporating RMS values as a novel parameter in the evaluation process. We anticipate that these findings will have practical implications, particularly in designing orthotic supports, specialized footwear for stroke patients, and the formulation of tailored rehabilitation programs within clinical settings.

Impact of splenectomy on circulating microparticles in patients with sickle cell anemia.

Circulating microparticles (MP) are being described as potential biomarkers for disease activity in a variety of conditions including sickle cell anemia (SCA). However, relatively little is known about the influence of spleen status on MP levels in patients with SCA. Using a prospective study design we characterize circulating MP in 144 patients with SCA in steady state by assessing their cellular origin and their relationships to spleen status defined by clinical and imaging findings. In addition, MP levels were studied according to demographic characteristics, clinical status, treatment modalities, and other hematological and biochemical parameters. Absolute plasma concentrations of MP were determined by flow cytometry. Patients with SCA displayed a 10-fold increase in levels of MP derived from red blood cell (RBC) and platelets (PLT) when compared to their healthy counterparts (p < 0.0001). Splenectomized patients with SCA have more pronounced levels of MPRBC and MPPLT, and remained elevated after several weeks of follow-up. Levels of MP were not significantly associated with spleen removal procedures, age, gender, clinical severity score, hydroxyurea therapy, hemoglobin F, and co-existence of glucose-6-phosphate dehydrogenase deficiency. Collectively, these results suggest that splenectomy affects circulating levels of MP regardless of the known SCA modifiers and correlates.

Development of a T-ARMS-PCR Assay for Detecting Genetic Polymorphism in the Catalase (rs7943316) Gene in the Iraqi Population with Breast Cancer.

Numerous investigations have demonstrated that oxidative stress is markedly increased in breast cancer patients compared to their healthy counterparts. Catalase (CAT), a crucial antioxidant enzyme, plays a pivotal role in safeguarding cells against oxidative damage initiated by reactive oxygen species (ROS). The CAT (rs7943316) gene encodes catalase, and certain genetic variations in this gene have been observed to modify catalase activity and levels. Such changes can lead to an altered response to oxidative stress, potentially increasing the risk of breast cancer. In light of this, a novel tetra-primer amplification-refractory mutation system (T-ARMS)-PCR assay was developed to investigate the possible correlation between the CAT (rs7943316) gene polymorphism and the development of breast cancer in patients. This method employs a one-step PCR, which is faster, more cost-effective, and more precise than existing techniques. Sanger sequencing was performed to validate the accuracy of our findings. The T-ARMS-PCR assay revealed a significant association between the A/T allele of the CAT (rs7943316) gene and breast cancer. Specifically, individuals with the TT genotype had a higher risk of developing breast cancer than those with the AA genotype. The T allele frequency was greater among breast cancer patients than in the control group, and genotype frequencies were consistent with the principles of the Hardy-Weinberg Equilibrium. This study is the first to showcase a rapid, cost-effective, and high-throughput method for detecting the SNP in the CAT (rs7943316) gene. This method has the potential to be employed in large-scale clinical trials.

Characterization of Lung Microbiomes in Pneumonic Hu Sheep Using Culture Technique and 16S rRNA Gene Sequencing.

Hu sheep, a locally bred species in China known for its high productivity, is currently suffering from pneumonia. Here, we combine high-throughput 16SrRNA gene sequencing and bacterial culturing to examine the bacterial community in pneumonic Hu Sheep lungs (p < 0.05). The results showed that the abundance and diversity of lung bacteria in healthy sheep were significantly higher than those in pneumonia sheep (p = 0.139), while there was no significant difference between moderate and severe pneumonia. Furthermore, the composition of the lung microbiota community underwent significant alterations between different levels of pneumonia severity. The application of LEfSe analysis revealed a notable enrichment of Mannheimiae within the lungs of sheep afflicted with moderate pneumonia (p < 0.01), surpassing the levels observed in their healthy counterparts. Additionally, Fusobacterium emerged as the prevailing bacterial group within the lungs of sheep suffering from severe pneumonia. Integrating the results of bacterial isolation and identification, we conclusively determined that Mannheimia haemolytica was the primary pathogenic bacterium within the lungs of sheep afflicted with moderate pneumonia. Furthermore, the exacerbation of pneumonia may be attributed to the synergistic interplay between Fusobacterium spp. and other bacterial species. Our results provide new insights for guiding preventive and therapeutic measures for pneumonia of different severities in sheep.

Association Between Maternal Thyroid Function in Early Pregnancy and Gestational Diabetes: A Prospective Cohort Study.

Previous studies on the relationship between thyroid gland function and the development of gestational diabetes mellitus (GDM) have reported different results, leading to the need for a cohort study design with a large sample size. We aimed to investigate the relationship between thyroid function in early pregnancy and GDM. This was a prospective cohort study based on the China Birth Cohort Study (CBCS), from February 2018 to December 2020. The study took place at a tertiary maternal and child health hospital. A total of 36 256 pregnant women were successfully recruited based on the CBCS. The main outcome measure was GDM. This study consisted of 26 742 pregnant women who met the inclusion criteria, of whom 3985 (14.90%) were diagnosed with GDM, and the women with GDM were older than their healthy counterparts (33.26 ± 4.01 vs 31.51 ± 3.76 years, P < .001). After removing potential influencing variables, we found that increased thyroid-stimulating hormone (TSH) (adjusted odds ratio [aOR] 1.030, 95% CI 1.007, 1.054, P = .012) and subclinical hypothyroidism (aOR 1.211, 95% CI 1.010, 1.451, P = .039), but not free thyroxine or thyroid peroxidase antibody, were associated with the occurrence of GDM. Further analysis indicated a nonlinear relationship between TSH and GDM (P < .05): when TSH ≤ 1.24 mIU/L, the occurrence of GDM was elevated with increasing TSH, but when TSH > 1.24 mIU/L, this trend was not obvious. High TSH might be associated with increased risk of GDM.

Hyperandrogenism Protects Against High Blood Pressure by Nongenomic Mechanisms and Obesity Causes Hypertension in Females with Polycystic Ovary Syndrome

ABSTRACT Background Androgens induce vasorelaxation and reduce blood pressure in different mammals, including humans. Most women with polycystic ovary syndrome (PCOS), with hyperandrogenism, are obese and exhibit hypertension; thus, the fact that androgens increase blood pressure (BP) is controversial. Our aim was to determine whether hypertension is produced by androgen excess and/or obesity. Methods Experiments were performed in dehydroepiandrosterone; (DHEA, s.c)-induced PCOS model. BP from nonobese and obese rats with PCOS (fed a normal or high-fat diet, respectively) was evaluated weekly for 10 weeks by plethysmography and compared between them. We determined whether androgen receptors are responsible for androgen action on BP in rats with PCOS; a group of DHEA-treated rats was implanted with pellets of an antiandrogen and was compared with nonobese rats with PCOS. Isometric tension from aortas of nonobese and obese rats was recorded and compared to explore the integrity of the vascular endothelium when acetylcholine-induced endothelium-dependent vascular relaxation on phenylephrine contraction. Additionally, BP was obtained from 30 women diagnosed with PCOS: nonobese (BMI ≤25) and obese women (BMI ≥35) and compared with healthy counterparts; 15 obese and 15 nonobese women. Results Nonobese rats and women with PCOS showed hypotension, while obese rats and women with PCOS displayed hypertension. Healthy obese women were hypertensive and nonobese women remained normotensive. Antiandrogen did not modify the BP values in nonobese rats with PCOS, and obese rats with PCOS revealed marked endothelial dysfunction. Conclusions Our findings show that obesity is responsible for hypertension in PCOS and partial endothelial damage was observed, which may contribute to elevated BP. Remarkably, hyperandrogenism is capable of regulating BP to low values that are androgen receptor-independent.

Exploring the gut microbiota in patients with pre-diabetes and treatment naïve diabetes type 2 - a pilot study

BackgroundCompared to their healthy counterparts, patients with type 2 diabetes (T2D) can exhibit an altered gut microbiota composition, correlated with detrimental outcomes, including reduced insulin sensitivity, dyslipidemia, and increased markers of inflammation. However, a typical T2D microbiota profile is not established. The aim of this pilot study was to explore the gut microbiota and bacteria associated with prediabetes (pre-T2D) patients, and treatment naïve T2D patients, compared to healthy subjects.MethodsFecal samples were collected from patients and healthy subjects (from Norway). The bacterial genomic DNA was extracted, and the microbiota analyzed utilizing the bacterial 16S rRNA gene. To secure a broad coverage of potential T2D associated bacteria, two technologies were used: The GA-map® 131-plex, utilizing 131 DNA probes complementary to pre-selected bacterial targets (covering the 16S regions V3-V9), and the LUMI-Seq™ platform, a full-length 16S sequencing technology (V1-V9). Variations in the gut microbiota between groups were explored using multivariate methods, differential bacterial abundance was estimated, and microbiota signatures discriminating the groups were assessed using classification models.ResultsIn total, 24 pre-T2D patients, 18 T2D patients, and 52 healthy subjects were recruited. From the LUMI-Seq™ analysis, 10 and 9 bacterial taxa were differentially abundant between pre-T2D and healthy, and T2D and healthy, respectively. From the GA-map® 131-plex analysis, 10 bacterial markers were differentially abundant when comparing pre-T2D and healthy. Several of the bacteria were short-chain fatty acid (SCFA) producers or typical opportunistic bacteria. Bacteria with similar function or associated properties also contributed to the separation of pre-T2D and T2D from healthy as found by classification models. However, limited overlap was found for specific bacterial genera and species.ConclusionsThis pilot study revealed that differences in the abundance of SCFA producing bacteria, and an increase in typical opportunistic bacteria, may contribute to the variations in the microbiota separating the pre-T2D and T2D patients from healthy subjects. However, further efforts in investigating the relationship between gut microbiota, diabetes, and associated factors such as BMI, are needed for developing specific diabetes microbiota signatures.

Antitumor activity of miR-188-3p in gastric cancer is achieved by targeting CBL expression and inactivating the AKT/mTOR signaling.

Altered miR-188-3p expression has been observed in various human cancers. To investigate the miR-188-3p expression, its roles, and underlying molecular events in gastric cancer. Fifty gastric cancer and paired normal tissues were collected to analyze miR-188-3p and CBL expression. Normal and gastric cancer cells were used to manipulate miR-188-3p and CBL expression through different assays. The relationship between miR-188-3p and CBL was predicted bioinformatically and confirmed using a luciferase gene reporter assay. A Kaplan-Meier analysis was used to associate miR-188-3p or CBL expression with patient survival. A nude mouse tumor cell xenograft assay was used to confirm the in vitro data. MiR-188-3p was found to be lower in the plasma of gastric cancer patients, tissues, and cell lines compared to their healthy counterparts. It was associated with overall survival of gastric cancer patients (P < 0.001), tumor differentiation (P < 0.001), lymph node metastasis (P = 0.033), tumor node metastasis stage (I/II vs III/IV, P = 0.024), and American Joint Committee on Cancer stage (I/II vs III/IV, P = 0.03). Transfection with miR-188-3p mimics reduced tumor cell growth and invasion while inducing apoptosis and autophagy. CBL was identified as a direct target of miR-188-3p, with its expression antagonizing the effects of miR-188-3p on gastric cancer (GC) cell proliferation by inducing tumor cell apoptosis and autophagy through the inactivation of the Akt/mTOR signaling pathway. The in vivo data confirmed antitumor activity via CBL downregulation in gastric cancer. The current data provides ex vivo, in vitro, and in vivo evidence that miR-188-3p acts as a tumor suppressor gene or possesses antitumor activity in GC.