Peripheral Levels Research Articles

Responses to the activation of different intranasal trigeminal receptors: Evidence from behavioral, peripheral and central levels

AimThere are various receptors that mediate intranasal trigeminal sensations. However, few studies compare the response patterns across different receptor activations. MethodsWe recorded negative mucosal potentials (NMPs) in 24 healthy participants and event-related potentials (ERPs) in 17 participants during exposure to five odors that trigger trigeminal sensations and one olfactory stimulus. Additionally, 10 participants completed a continuous odor intensity rating task. ResultsWe observed a significant effect of odor type on NMP amplitudes (F=13.51 to 21.88, p’s<0.01), with cyclohexanone (TRPV1) and CO2 (TRPV1+A1) inducing greater N1 and/or P1N1 amplitudes than other stimuli (t=3.28 to 7.54, p’s<0.05). Similar differences were seen in ERP amplitudes (F=3.69 to 12.25, p’s<0.05), with cyclohexanone showing greater P2 and/or N1P2 amplitudes than PEA (odorant), carvacrol (TRPV3+A1), and perillaldehyde (TRPA1) (t=3.13 to 4.10, p’s<0.05). CO2 also produced greater amplitudes than carvacrol (t=3.53 to 4.42, p’s<0.05). In the odor intensity rating task, cyclohexanone, CO2, and isopulegol (TRPM8+TRPA1) had higher peak ratings, steeper slopes, and/or shorter latencies (F=6.15 to 13.86, p’s<0.01; t=3.14 to 7.76, p’s<0.05). ConclusionsActivation of different intranasal trigeminal receptors yields varied responses. Notably, stimuli involving TRPV1 activation, linked to irritation or pain, elicited stronger behavioral and neural activity compared to stimuli involving other receptors, even when controlling for rated stimulus intensity. This emphasizes TRPV1’s significance in survival adaptation. Future studies should test different sets of stimulants to verify the robustness of these findings.

Effects of psychoplastogens on blood levels of brain-derived neurotrophic factor (BDNF) in humans: a systematic review and meta-analysis.

Peripheral levels of brain-derived neurotrophic factor (BDNF) are often used as a biomarker for the rapid plasticity-promoting effects of ketamine, psychedelics, and other psychoplastogens in humans. However, studies analyzing peripheral BDNF after psychoplastogen exposure show mixed results. In this meta-analysis, we aimed to test whether the rapid upregulation of neuroplasticity seen in preclinical studies is detectable using peripheral BDNF in humans. This analysis was pre-registered (PROSPERO ID: CRD42022333096) and funded by the University of Fribourg. We systematically searched PubMed, Web of Science, and PsycINFO to meta-analyze the effects of all available psychoplastogens on peripheral BDNF levels in humans, including ketamine, esketamine, LSD, psilocybin, ayahuasca, DMT, MDMA, scopolamine, and rapastinel. Risk of bias was assessed using Cochrane Risk of Bias Tools. Using meta-regressions and mixed effects models, we additionally analyzed the impact of several potential moderators. We included 29 studies and found no evidence that psychoplastogens elevate peripheral BDNF levels in humans (SMD = 0.024, p = 0.64). This result was not affected by drug, dose, blood fraction, participant age, or psychiatric diagnoses. In general, studies with better-controlled designs and fewer missing values reported smaller effect sizes. Later measurement timepoints showed minimally larger effects on BDNF. These data suggest that peripheral BDNF levels do not change after psychoplastogen administration in humans. It is possible that peripheral BDNF is not an informative marker of rapid changes in neuroplasticity, or that preclinical findings on psychoplastogens and neuroplasticity may not translate to human subjects. Limitations of this analysis include the reliability and validity of BDNF measurement and low variation in some potential moderators. More precise methods of measuring rapid changes in neuroplasticity, including neuroimaging and stimulation-based methods, are recommended for future studies attempting to translate preclinical findings to humans.

The association between chemosensitivity and the 10-year risk of type 2 diabetes in male patients with obstructive sleep apnea

PurposeObstructive sleep apnea (OSA) is associated with a variety of diseases, including type 2 diabetes (T2D). Chemosensitivity is an important component of the pathophysiological mechanisms of OSA, and it is not only elevated in patients with OSA but also in those with T2D. This study aimed to investigate the association between chemosensitivity and the risk of developing T2D in patients with OSA.MethodsA total of 135 male participants with OSA and without pre-existing T2D were enrolled in this study. Peripheral chemosensitivity was evaluated using the rebreathing test. Data on demographics, polysomnographic parameters, and clinical characteristics were collected. The QDiabetes-2018 risk calculator was employed to calculate the 10-year T2D risk. The association between peripheral chemosensitivity and 10-year T2D risk was examined using multivariate logistic regression.ResultsA total of 64 participants had moderate-to-high 10-year risk of T2D. In the fully adjusted model, participants situated within the second and fifth quantiles of peripheral chemosensitivity levels demonstrated a higher risk of developing T2D, with OR of 4.87 (95% CI, 1.22–19.43) and 5.26 (95% CI, 1.27–21.68) respectively. However, across varying levels of peripheral chemosensitivity, no significant difference in the 10-year T2D risk was observed among different severities of OSA.ConclusionHigher peripheral chemosensitivity was associated with an increased 10-year T2D risk, as calculated using a risk calculator based on clinical variables. For outcomes that reflect a moderate-to-high 10-year risk of T2D, the severity of OSA did not significantly affect the risk, irrespective of whether patients exhibited relatively low or high chemosensitivity.

Establishment and evaluation of a risk prediction model for coronary heart disease in primary Sjögren’s syndrome based on peripheral blood IL-6 and Treg percentages

ObjectiveThis study aims to establish and evaluate a risk prediction model for coronary heart disease (CHD) in patients with primary Sjögren’s syndrome (pSS) based on peripheral blood levels of interleukin-6 (IL-6) and the percentage of regulatory T cells (Treg%). This model is intended to facilitate the timely identification of high-risk patients and the implementation of preventive measures.MethodsClinical data were collected from 120 pSS patients who visited the Second Hospital of Shanxi Medical University between November 2021 and September 2023. Patients were classified into pSS and pSS-CHD groups according to CHD diagnostic criteria. Peripheral blood lymphocyte subsets and cytokine levels were assessed using flow cytometry. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors, and a nomogram was constructed based on these factors. The model’s discriminatory ability, calibration, and clinical utility were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis.ResultsThe univariate and multivariate logistic regression analyses identified several independent risk factors for CHD in pSS patients: erythrocyte sedimentation rate (ESR) (OR=1.10, P=0.019), triglycerides (TG) (OR=3.67, P=0.041), IL-6 (OR=1.29, P=0.048), and Treg% (OR=0.25, P=0.004). A nomogram incorporating these factors demonstrated an area under the curve (AUC) of 0.96, indicating excellent predictive performance, and showed good calibration (P=0.599), suggesting significant clinical applicability. Furthermore, Treg% exhibited a negative correlation with cholesterol (CHOL) and low-density lipoprotein cholesterol (LDL-C) levels, while IL-6 showed a positive correlation with CHOL and LDL-C levels. TG was positively correlated with C-reactive protein (CRP).ConclusionThis study successfully developed a risk prediction model based on peripheral blood IL-6 and Treg% levels, providing critical evidence for the early identification and personalized prevention of CHD in pSS patients, with potential clinical implications.

Influence of the ligation sequence of the inferior mesenteric artery and vein on circulating tumor cells in laparoscopic rectal cancer surgery: a prospective pilot study

BackgroundThere is no regulation in the current guidelines on the sequence of ligation of the inferior mesenteric artery and vein during rectal cancer surgery owing to a lack of sufficient evidence. Circulating tumor cells (CTCs) in peripheral blood can be used as potential indicators for predicting prognosis in colorectal cancer patients. This study aims to explore the feasibility of different ligation sequences for the inferior mesenteric vessels and their potential influence on CTCs.MethodsThis pilot study involved 29 stage I-III rectal adenocarcinoma patients undergoing laparoscopic surgery. Patients were allocated into two groups based on the sequence of vascular ligation: vein-first (V-first) and artery-first (A-first). The primary objective was to assess the impact of the ligation sequence on peripheral blood CTC levels pre- and post-operatively. Secondary outcomes included intraoperative complications, surgical duration, blood loss, and number of lymph nodes harvested, and postoperative complications. The study was approved by the ethics committee of our hospital (SCCHEC-02-2024-102), and all patients provided informed consent.ResultsNo significant differences were found between the two groups regarding surgical duration, blood loss, lymph nodes harvested, or postoperative complications. A reduction in CTCs postoperatively was observed in 36% of patients in the V-first group, in comparison to 20% in the A-first group.ConclusionBoth A-first and V-first ligation sequences are viable and safe options in laparoscopic rectal cancer surgery. The V-first approach may be more effective in reducing levels of CTCs in peripheral blood. Further randomized studies are warranted to explore these findings comprehensively.

Research progress on analgesic mechanism of acupuncture for cancer pain

Cancer pain is one of the common complications in patients with intermediate or advanced cancer, which brings severe sufferings to patients and their families, and also seriously interferes with the anti-tumor process. Acupuncture is an effective method for the treatment of cancer pain, which has the advantages of simple operation, quick effect and fewer side effects, and is widely used in clinic. In this paper, we reviewed the relevant literature on the mechanisms of acupuncture in the treatment of cancer pain both at home and abroad in recent years, and summarized the analgesic mechanisms of acupuncture for cancer pain from the peripheral level and the central level. It is found that acupuncture can relieve cancer pain by regulating immune inflammatory response, expression of ion channels and pain-related receptors, remising central sensitization, activating endogenous pain modulating system and suppressing pain transmission pathways. In addition, we also think that the use of high-throughput multi-omics techniques and neuroimaging methods to detect and analyze the brain areas or body fluids before and after acupuncture should be the focus of acupuncture analgesia research in the future.

Hemochromatosis neural archetype reveals iron disruption in motor circuits.

Our understanding of brain iron regulation and its disruption in disease is limited. Excess iron affects motor circuitry, contributing to Parkinson's disease (PD) risk. The molecular mechanisms regulating central iron levels, beyond a few well-known genes controlling peripheral iron, remain unclear. We generated scores based on the archetypal brain iron accumulation observed in magnetic resonance imaging scans of individuals with excessive dietary iron absorption and hemochromatosis risk. Genome-wide analysis revealed that this score is highly heritable, identifying loci associated with iron homeostasis, and driven by peripheral iron levels. Our score predicted gait abnormalities and showed a U-shaped relationship with PD risk, identifying individuals with threefold increased risk. These results establish a hormetic relationship between brain iron and PD risk, where central iron levels are strongly determined by genetics via peripheral iron. This framework combining forward and reverse genetics is a powerful study design to understand genomic drivers underlying high dimensional phenotypes.

Associations of HMGB1, sTNFR-1 and NLR with Premature Delivery Secondary to Infection in Pregnant Women Undergoing Cervical Cerclage

Background: Although cervical cerclage has improved with the rapid development of medical technology, there remains a distinct probability of adverse pregnancy outcomes. To investigate the associations of changes in the high mobility group box 1 (HMGB1), soluble tumor necrosis factor receptor 1 (sTNFR-1) and peripheral blood neutrophil-to-lymphocyte ratio (NLR) with premature delivery secondary to infection in pregnant patients undergoing cervical cerclage. Methods: Sixty-seven pregnant patients with premature delivery after cervical cerclage, who were treated at the Affiliated Matern &amp; Child Care Hospital of Nantong University from January 2022 to October 2023, were enrolled, including 43 with premature delivery secondary to infection (infectious group) and 24 with idiopathic premature delivery (non-infectious group). The pre-delivery serum levels of HMGB1, sTNFR-1 and the peripheral blood level of NLR were compared between the 2 groups. Further, the clinical value of these 3 indicators in predicting premature delivery secondary to infection among pregnant patients undergoing cervical cerclage was assessed by receiver operating characteristic (ROC) curve analysis. Results: The infectious group exhibited significantly higher serum levels of HMGB1, sTNFR-1 and peripheral blood level of NLR compared to those in the non-infectious group, demonstrating significant differences (p &lt; 0.05). Logistic regression analysis revealed that HMGB1 and NLR were independent influencing factors for premature delivery (p &lt; 0.05). According to the ROC curve analysis results, the changes in HMGB1, sTNFR-1 and NLR levels may reflect the risk of premature delivery secondary to infection among pregnant patients undergoing cervical cerclage. The area under the curve (AUC), sensitivity and specificity of combined detection were all markedly higher than those of independent detection. Conclusions: HMGB1, sTNFR-1 and NLR levels are risk factors for third-trimester premature delivery among pregnant patients undergoing cervical cerclage. Timely combined detection of serum HMGB1, sTNFR-1 and peripheral blood NLR during the third trimester can improve the clinical diagnostic acumen, which enables early prevention to help lower the risk of premature delivery.

Correlation of the abundance of MDSCs, Tregs, PD-1, and PD-L1 with the efficacy of chemotherapy and prognosis in gastric cancer.

The aim of this study was to investigate the relationship between tumor microenvironment markers (myeloid-derived suppressor cells [MDSCs], regulatory T cells [Tregs], programmed cell death 1 [PD-1], and programmed death ligand 1 [PD-L1]) and chemotherapy efficacy and prognosis in advanced gastric cancer, identifying potential monitoring indicators. Advanced gastric cancer patients' MDSC and Treg expression was measured by flow cytometry pre- and postchemotherapy; PD-1 and PD-L1 expression in cancer tissues was assessed by immunohistochemistry. Correlations with chemotherapy outcomes and prognosis were analyzed. Postchemotherapy reductions in MDSC and Treg levels correlated with chemotherapy efficacy (P <.01). Negative PD-1 and PD-L1 expression in cancer tissues predicted better chemotherapy responses (P <.01). Patients with lower MDSC and Treg levels and negative PD-1 and PD-L1 had significantly longer median progression-free survival (PFS) and overall survival (OS) (P <.05). In advanced gastric cancer, reduced peripheral blood MDSC and Treg levels postchemotherapy and negative PD-1 and PD-L1 expression in tissues are associated with improved chemotherapy efficacy and are independent prognostic factors for PFS and OS.

Weight discrimination ability during an action observation task is dependent on the type of muscle contraction

AbstractConcentric and eccentric contractions show different patterns of neural activity at both peripheral and cortical levels, which are thought to influence the perception of action properties such as the weight of objects moved by others. The aim of this study was to investigate how the type of muscle contraction influences weight estimation during action observation.Forty‐eight volunteers completed the Main experiment and the Control experiment. In the Main experiment, they performed a weight discrimination video task in which they watched videos of an actor moving two objects, a comparison, and a reference box, executing concentric or eccentric contractions and they had to indicate which box was the heaviest. Sensitivity analysis and psychometric functions were used to analyse the data. In the Control experiment, observers judged the actor's effort in moving the boxes.The results of the Main experiment showed that the weight discrimination sensitivity was higher in the eccentric condition for the light boxes. Conversely, for the heaviest boxes, discrimination sensitivity was higher in the concentric condition. These results were confirmed by the psychometric function analysis. The control experiment showed that the perceived difference in effort between the comparison and reference stimuli was greater in the eccentric than in the concentric condition for light stimuli.These results showed that the ability to evaluate the weight of the object involved in the observed action was influenced by the type of contraction and the amount of weight. The effort attributed to the actor influenced the observer's perception.

Evaluation of the cell death markers for aberrated cell free DNA release in high altitude pulmonary edema.

The effect of high altitude (HA, altitude >2500 m) can trigger a maladaptive response in unacclimatized individuals, leading to various HA illnesses such as high altitude pulmonary edema (HAPE). The present study investigates circulating cell free (cf) DNA, a minimally invasive biomarker that can elicit a pro-inflammatory response. Our earlier study observed altered cfDNA fragment patterns in HAPE patients and the significant correlation of these patterns with peripheral oxygen saturation levels. However, the unclear release mechanisms of cfDNA in circulation limit its characterization and clinical utility. The present study not only observed a significant increase in cfDNA levels in HAPE patients (27.03 ± 1.37 ng/ml; n = 145) compared to healthy HA sojourners (controls, 14.57 ± 0.74 ng/ml; n = 65) and highlanders (HLs, 15.50 ± 0.8 ng/ml; n = 34) but also assayed the known cell death markers involved in cfDNA release at HA. The study found significantly elevated levels of the apoptotic marker, annexin A5, and secondary necrosis or late apoptotic marker, High mobility group box 1, in HAPE patients. In addition, we observed ahigher oxidative DNA damage marker, 8-hydroxy-2'-deoxyguanosine, in HAPE compared to controls, suggestive of the role of oxidative DNA status in promoting the inflammatory potential of cfDNA fragments and their plausible role in manifesting HAPE pathophysiology. Extensive in vitro future assays can confirm theimmunogenic role of cfDNA fragments that may act as a danger-associated molecular pattern and associate with markers of cellular stresses in HAPE.

Analysis of gastric cancer medication by exploring fluorouracil drugs

Abstract. Gastric cancer (GC), as one of the most important types of cancer with a very high incidence rate in China, is in urgent need of treatment. China has made certain progress, such as the widespread use of fluorouracil and other drugs in the treatment of gastric cancer, as well as the use of various treatment methods such as surgery and chemotherapy. This article aims to explore the efficacy of fluorouracil drugs in the treatment of gastric cancer and their combined application with other drugs. By analyzing the correlation between peripheral blood platelet levels and the efficacy of oxaliplatin combined with fluorouracil chemotherapy in gastric cancer patients, as well as the effects of two chemotherapy regimens, docetaxel combined with oxaliplatin, tigio and docetaxel combined with cisplatin and fluorouracil, on advanced gastric cancer, it was found that fluorouracil drugs, as cell cycle inhibitors, have an inhibitory effect on cell division and have a significant effect in the treatment of gastric cancer. Future research can further deepen the combined application of fluorouracil drugs with other drugs to reduce complications and improve treatment effectiveness. It is suggested that future research should focus on in-depth exploration of targeted drug delivery, combined with new biotechnology, to improve the efficiency and accuracy of gastric cancer treatment.

Irisin Improves Preeclampsia by Promoting Embryo Implantation and Vascular Remodeling.

Preeclampsia is a pregnancy-specific disorder with unclear pathogenesis. Irisin, a recently identified exercise-induced factor, significantly influences lipid metabolism and cardiovascular function. Nonetheless, its role in trophoblast development during human placentation and the related intracellular signaling pathways remain poorly understood. We assessed peripheral blood irisin expression in early pregnancy among patients with preeclampsia and its correlation with key clinical indicators. In trophoblast cell lines and mice, we used exogenous irisin and viral knockdown to investigate functional changes. Phosphorylation-specific antibody arrays and dual-luciferase reporter assays were used to explore downstream molecular mechanisms, which were subsequently validated in trophoblast cell lines and relevant gene knockout mice. In early pregnancy, patients with preeclampsia exhibit decreased peripheral blood irisin levels, occurring earlier than traditional predictive markers, such as PLGF (placental growth factor) and sFlt-1 (soluble fms-like tyrosine kinase-1). Furthermore, irisin concentration is positively correlated with proteinuria and abnormal blood pressure during pregnancy. Exogenous irisin significantly enhanced trophoblast cell migration, invasion, and proliferation while inhibiting apoptosis. It also increased STAT (signal transducers and activators of transcription) 4 phosphorylation and its binding to the GLUT (glucose transporter)-3 promoter, resulting in elevated GLUT-3 expression and glucose uptake in trophoblast cells. In vivo, increased peripheral irisin promoted embryo implantation, vascular remodeling, and enhanced glucose uptake, whereas reduced irisin resulted in a preeclampsia-like phenotype characterized by elevated blood pressure, proteinuria, renal-placental dysfunction, adipose accumulation, and restricted fetal growth. Peripheral irisin improves preeclampsia by promoting embryo implantation and vascular remodeling through the activation of the STAT4/GLUT-3 pathway. Reduced peripheral irisin may contribute to preeclampsia-like pathologies. This study supports the advocacy for appropriate exercise during early pregnancy and provides new insights for preeclampsia prevention.

NCOG-28. SERUM PROTEIN BIOMARKERS LINKED TO NEURODEGENERATIVE PROCESSES ARE ELEVATED IN GLIOMA PATIENTS AND ASSOCIATED WITH SEVERITY OF NEUROLOGIC SYMPTOMS

Abstract BACKGROUND Glioma patients frequently report neurologic symptoms, adding to the complexity of cancer management and negatively impacting quality of life. However, mechanisms associated with the development of neurologic symptoms in glioma patients remain unclear. Pathological changes in the brain of glioma patients might result in elevated peripheral blood levels of proteins previously linked to central nervous system (CNS) damage and neurodegeneration, including neurofilament light chain (NfL), tau, and glial fibrillary acidic protein (GFAP). Here, we tested the hypothesis that the circulating levels of these proteins in blood are elevated in glioma patients and associated with the severity of neurologic symptoms. METHODS Patients (n=73) were enrolled in a natural history study (NCT02851706, PI T. Armstrong). Healthy subjects (n=39) were recruited by the National Institutes of Health Clinical Center Blood Bank. Neurologic symptom severity and walking interference were assessed using MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT). Serum proteins were analyzed using ultrasensitive assays (Meso Scale Discovery). RESULTS Participants were predominantly white (patients 74%, healthy subjects 67%) and male (patients 58%, healthy subjects 54%). The median age was 44 (range=24,74) for patients and 49 (range=19,78) for healthy volunteers. No significant differences in age, sex, or race were observed between patients and healthy subjects. Serum levels of NfL (p&amp;lt;0.0001), GFAP (p&amp;lt;0.0001), and tau (p&amp;lt;0.0001) were higher in glioma patients when compared to healthy subjects. Patients with walking interference had higher levels of GFAP (p=0.003), NfL (p=0.003), and tau (p=0.004), and those who reported numbness had higher levels of GFAP (p=0.012). CONCLUSIONS These findings suggest that serum levels of protein markers of neurodegeneration are elevated in glioma patients and associated with the presence of neurologic symptoms. Blood-based biomarkers have the potential to shed light on the mechanisms underlying symptoms and offer a non-invasive alternative for monitoring CNS damage that impact patient outcomes.

Blood lipid profiles associated with metastatic sites in advanced gastric cancer

BackgroundThis study explored the correlation between peripheral blood lipid levels and clinicopathological parameters in patients with advanced gastric cancer (GC), focusing on changes in lipid levels during disease progression.MethodsPathological features and serum lipid profiles of 179 patients with stage III-IV gastric adenocarcinoma were analyzed. Lipid parameters examined included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), apolipoprotein AI (Apo AI), apolipoprotein B (Apo B), lipoprotein(a) (Lp(a)), among others. The total cholesterol-lymphocyte score (TL score) and BMI were also calculated. The association between lipid parameters and clinicopathological characteristics such as age, gender, family history, and metastasis sites was assessed.ResultsIn GC patients, females had higher TG levels than males. Patients with peritoneal metastasis had significantly lower levels of TC, LDL-C, Apo B, and B/A ratio. Those with lung metastasis exhibited higher LDL-C levels and lower levels of VLDL-C. No significant associations were found between lipid levels and metastasis to distant lymph nodes, liver, or bone. Female patients with ovarian metastasis had significantly lower VLDL-C levels. Multivariate analysis revealed low TC as an independent risk factor for peritoneal metastasis, high LDL-C and low VLDL-C levels for lung metastasis, and younger age and low VLDL-C for ovarian metastasis.ConclusionSpecific blood lipid levels are significantly associated with metastatic sites in advanced gastric cancer. Lipid profiles could serve as potential biomarkers for predicting metastatic sites in GC patients.

The proteome and metabolome changes distinguish the effect of dietary energy levels on the development of ovary in chicken during sexual maturity

To deeply understanding the impact of peripheral energy level on the development of ovaries during the sexual maturation of chicken, in this study, the ovaries and serum of sexually mature and immature chickens at the same age from different energy level groups were collected, and the proteome and metabolome were detected. The results of ovarian and serum metabolomics revealed that dietary energy levels affected the energy metabolism and fatty acid oxidation of ovary in chicken, including the up-regulated expression of dihydroacetone phosphate and α-linolenic acid in high energy level groups. The results of proteomics showed that peripheral energy levels affected the catecholamine biosynthesis and metabolism in ovary before sexual maturation. The integrating analysis revealed that increased energy flux may influence ovarian development by regulating cholesterol reserves and steroid hormone synthesis in the ovaries. In vitro, the cultivation of chicken primary granulosa cells showed that sterol carrier protein 2 played a role in fatty acid synthesis and metabolism but did not significantly affect progesterone synthesis. Overall, dietary energy levels may be involved in the development of the ovaries during sexual maturation by influencing energy metabolism, biosynthesis of unsaturated fatty acids and steroid hormone within the ovaries.

Mediation effect of peripheral blood inflammatory factors in the association between severity of nonlactating mastitis and glycemic abnormalities

Background: The association between severity of non-lactating mastitis and glycemic abnormalities was analyzed to investigate the mediating role of peripheral inflammatory factor levels in the association. Methods: A total of 337 cases were included in this study, including 195 cases in the control group and 142 cases in the case group. Multifactorial logistic regression was used to analyze the associations between the severity of NLM and glycemic abnormality and peripheral inflammatory factors, and a mediation model was used to explore the mediating roles of the levels of hs-CRP, WBC, and IL-6 in the associations between the two. Results: The inflammatory factors IL-6, WBC, and hs-CRP had mediating effects, with effect values of 0.009 (0.003-0.038), 0.006(0.001-0.047), and 0.007(0.001-0.051), and mediating effect percentages of 2.38%, 2.12%, and 2.24%, respectively. Conclusion: NLM severity and glycemic abnormalities were positively correlated with peripheral inflammatory factors, and peripheral inflammatory factors played a partial mediating role in the association.

Increased dopamine D2/D3 receptor and serotonin transporter availability in male rats after spontaneous remission from repeated social defeat-induced depression; a PET study in rats

Most pharmacological treatments for depression target monoamine transporters and about 50 % of treated patients attain symptomatic remission. Once remission is attained, it is hard to distinguish the changes on brain monoaminergic transmission induced by the antidepressants, from those associated to remission per se. In this study, we aimed at studying the brain of spontaneously remitted rats from repeated social defeat (RSD)-induced depression in terms of dopamine D2/D3 receptor and serotonin transporter (SERT) availability, showing absence of depressive symptoms 2 weeks after RSD. We combined behavioral tests and positron emission tomography (PET) with [11C]raclopride and [11C]DASB to explore the changes in dopamine D2/D3 receptor and serotonin transporter (SERT) availability, respectively. Male rats submitted to RSD showed increased peripheral corticosterone levels, decreased body weight and anhedonia, as measured with the sucrose preference test, 1 day after RSD, confirming depressive-like symptoms. These depressive-like symptoms were no longer present 2 weeks after RSD. Rats that recovered from depressive-like symptoms showed decreased D2/D3 receptor binding in the caudate putamen and increased SERT availability in the brainstem, insular cortex, midbrain and thalamus, compared to control non-stressed animals. Our study shows that remission of depressive-like symptoms does not just “normalize” monoaminergic transmission, as changes in dopaminergic and serotonergic neurotransmission linger in several brain regions even after depressive-like symptoms have already resolved. These results provide new insights into the brain changes associated to remission in the RSD-induced depression model in rats.

Clinical Relevance of Oxidative Stress Biomarkers in Human Flavivirus Infections as Predictors of Disease Progression and Severity.

Several Flaviviridae constitute an emerging threat to global health because of their continuing spread and the expansion of vector habitats, largely driven by climate change and intensified global travel. Infections can result in severe neurological or visceral pathologies. The relationship between oxidative stress (OS), an imbalance between generated reactive oxygen species and the antioxidant defences of the host, and flavivirus infection has been repeatedly demonstrated in in vitro and animal studies, but measuring biomarkers of oxidative stress in vivo could prove useful in clinical patient management. We summarise the knowledge and prospects of measuring peripheral OS biomarker levels for clinical case management and correlation with disease severity in six important human flavivirus infections (dengue virus (DENV), Japanese encephalitis virus, West Nile virus (WNV), tick-borne encephalitis virus (TBEV), yellow fever virus and zika virus). We searched the Medline and Web of Science databases for 'Oxidative Stress' AND 'Biomarkers' AND 'Flavivirus', combined with 'clinical', 'in vivo/in vivo', 'patient' and/or 'disease' and included 43 peer-reviewed publications. Correlation between OS and infection has been studied in all six Flaviviridae, but most clinically relevant data are available for DENV, TBEV and WNV. Plasma protein carbonyls, glutathione peroxidase activity and nitrogen monoxide are promising prognostic markers, but their measurement would benefit from methodological harmonisation. Future studies should investigate a broad range of OS biomarkers as predictors of clinically relevant outcomes. We advocate the validation and use of universal or disease-specific oxidative stress indexes that incorporate the most significant outcomes into one, easy-to-use clinical determinant.

Short and Medium Chain Fatty Acids in a Cohort of Naïve Multiple Sclerosis Patients: Pre- and Post-Interferon Beta Treatment Assessment.

Alterations in intestinal permeability and microbiota dysregulation have been linked to the development of multiple sclerosis (MS). Short-chain fatty acids (SCFA) and medium-chain fatty acids (MCFA) are products of gut bacteria fermentation which are involved in immune regulation processes. In MS, SCFA have important immunomodulatory properties both in the periphery and the central compartment. Interferon β (IFNβ) was the first disease-modifying therapy approved for the treatment of MS and its effects on the gut microbiota are not fully elucidated. We performed a prospective observational study aimed to assess peripheral levels of SCFA and MCFA in 23 newly diagnosed, treatment-naïve MS patients (nMS) before and after one year of IFNβ treatment and 23healthy controls (HC). We investigated their associations with inflammation, interleukin-10 (IL-10), and blood-brain barrier permeability, matrix metalloproteinase 9 (MMP9). No significant differences in SCFA/MCFA levels were observed between baseline and after IFNβ treatment. Caproic acid levels were significantly higher in nMS compared to HC (1.64 vs 1.27µM, p=0.005). The butyric acid/caproic acid ratio was higher in HC compared to nMS (5.47 vs 2.55, p=0.005). Correlation analysis revealed associations between SCFA/MCFA levels and inflammatory biomarkers. nMS have a higher gut-inflammatory activity as seen by the caproic acid ratio as opposed to HC. In this cohort, IFNβ does not appear to modify the peripheral SCFA/MCFA levels after one year of treatment. The quantifications of peripheral SCFA/MCFA may prove to be a useful biomarker for gut-brain axis disruption in MS patients.