Serum Levels Research Articles

Heterogeneity of SARS-CoV-2 immune responses after the nationwide Omicron wave in China.

It remains unclear how previous infections and vaccinations influenced and shaped heterogeneous immune responses against Omicron and its variants in diverse populations in China. After the national wave of Omicron in early 2023, we evaluated serum levels of neutralizing antibodies (nAbs) against Omicron (B.1.1.529) and its variants (BA.5, BF.7, and CH1.1) in 33 COVID-19 convalescents and 40 uninfected vaccinees, using vesicular stomatitis virus-based pseudovirus neutralizing assay. In addition, we followed 34 Delta convalescent patients to compare their immune responses against Omicron before (late 2021) and after the Omicron wave (early 2023). NAbs at the acute phase of the disease were investigated in 50 Omicron inpatients, including 24 vaccinated and 26 unvaccinated patients. Among them, nasal mucosal IgA levels were measured in 42 subjects. Compared to vaccination, breakthrough infections significantly increased the breadth and magnitude of serum nAbs and mucosal IgA levels against Omicron variants. Exposure to Omicron but not Delta elicited stronger pan-Omicron responses. In Omicron inpatients, nAbs continued to rise as vaccination doses increased. However, in both vaccinees and convalescents, a fourth dose vaccination did not elicit higher nAbs against Omicron. Furthermore, nAbs against Omicron variants lasted longer than nAbs against WT SARS-CoV-2. Breakthrough infections of Omicron variants elicited specific immune responses against Omicron compared to vaccination and Delta infection. Although repeated vaccination revealed limited impacts on serum nAbs, populations at high risk of hospitalization may still benefit from continued vaccination.IMPORTANCEThe study described the specific humoral immunity against Omicron and its variants (BA.5, BF.7, and CH1.1) in diverse populations, including Delta-positive convalescent patients, Omicron-infected patients with a previous or current confirmed Delta infection, Omicron-positive patients, and healthy controls. In addition, we followed Delta convalescents for 1 year to evaluate the effect of a booster vaccine, breakthrough infection, and reinfection. Nasal mucosal IgA levels against SARS-CoV-2 were also examined. The findings of this study demonstrated the varied responses of individuals in different states following the outbreak of Omicron, highlighting the potential advantages of ongoing immunization for groups that are more vulnerable and have a greater likelihood of being hospitalized.

Dual-factor model of sleep and diet: a new approach to understanding central fatigue

BackgroundNumerous studies have recently examined the impact of dietary factors such as high-fat diets on fatigue. Our study aims to investigate whether high-fat diet (HFD) alone or combined with alternate-day fasting (ADF) can lead to the central fatigue symptoms and to investigate the potential integration of dietary and sleep variables in the development of central fatigue models.MethodsSeventy-five male Wistar rats were divided into five groups: control, HFD, HFD + ADF, modified multiple platform method (MMPM), and MMPM+HFD + ADF. Each group underwent a 21-day modeling period according to their respective protocol. Their behavioral characteristics, fatigue biochemical markers, hippocampal pathological changes, mitochondrial ultrastructure, and oxidative stress damage were analyzed.ResultsOur findings demonstrate that using only HFD did not cause central fatigue, but combining it with ADF did. This combination led to reduced exercise endurance, decreased locomotor activity, impaired learning and memory abilities, along with alterations in serum levels of alanine aminotransferase (ALT), creatine kinase (CK), and lactate (LAC), as well as hippocampal pathological damage and other central fatigue symptoms. Moreover, the MMPM+HFD + ADF method led to the most obvious central fatigue symptoms in rats, including a variety of behavioral changes, alterations in fatigue-related biochemical metabolic markers, prominent pathological changes in hippocampal tissue, severe damage to the ultrastructure of mitochondria in hippocampal regions, changes in neurotransmitters, and evident oxidative stress damage. Additionally, it was observed that rats subjected to HFD + ADF, MMPM, and MMPM+HFD + ADF modeling method exhibited significant brain oxidative stress damage.ConclusionWe have demonstrated the promotive role of dietary factors in the development of central fatigue and have successfully established a more stable and clinically relevant animal model of central fatigue by integrating dietary and sleep factors.

GDF-15 predicts epithelioid hemangioendothelioma aggressiveness and is down-regulated by sirolimus through ATF4/ATF5 suppression.

Epithelioid hemangioendothelioma (EHE) poses a therapeutic challenge due to limited efficacy of conventional chemotherapy in advanced cases, necessitating exploration of new treatment avenues and identification of novel aggressiveness biomarkers. This study aimed at i) utilizing an EHE patient-derived xenograft (PDX) model and its associated cell line to assess the efficacy of sirolimus and ii) analyzing two distinct patient cohorts to pinpoint circulating biomarkers of EHE aggressiveness. A PDX model and corresponding cell line were established from an advanced EHE patient, demonstrating consistency with the original tumor in terms of histomorphology, WWTR1::CAMTA1 fusion presence, and genomic and transcriptomic profiles. Two independent patient series were employed to investigate the association between Growth/Differentiation Factor 15 (GDF-15) serum levels and EHE aggressiveness. ELISA analyses on EHE cell culture medium and blood from EHE-carrying mice revealed the release of GDF-15 by EHE cells. Sirolimus exhibited markedly higher anti-tumor activity compared to doxorubicin, concurrently reducing GDF-15 expression/release both in vivo and in vitro. This reduction was attributed to the drug-induced inhibition of phosphorylation/activation of 4E-BP1 and subsequent downregulation of the GDF-15 transcription factors ATF4 and ATF5. Blood sample analyses from two independent patient series showed a significant correlation between GDF-15 and EHE aggressiveness. This study identifies GDF-15 as a novel biomarker of EHE aggressiveness and underscores the superior efficacy of sirolimus compared to doxorubicin in our experimental models. The observed inhibition of GDF-15 release by sirolimus suggests its potential as a biomarker for monitoring the drug's activity in patients.

Unique Sterol Metabolite Shifts in Inflammatory Bowel Disease and Primary Sclerosing Cholangitis

Inflammatory bowel disease (IBD) triggers chronic intestinal inflammation and is linked to primary sclerosing cholangitis (PSC). Cholesterol homeostasis, tightly regulated under normal conditions, becomes disrupted in both inflammation and chronic liver disease. We analyzed fecal and serum levels of cholesterol synthesis precursors, oxysterols, and phytosterols in 87 patients with IBD (81 for serum analysis) including patients with Crohn's disease (CD) and ulcerative colitis (UC), 11 patients with PSC, 21 patients with PSC-IBD (18 for serum analysis), and 16 healthy controls (17 for serum analysis). Cholesterol was analysed by flow injection analysis on a high-resolution hybrid quadrupole-Orbitrap mass spectrometer and further serum sterols and all fecal sterols were analysed by a gas chromatograph mass spectrometer. Serum levels of lanosterol, 7-dehydrocholesterol, 7-beta-hydroxycholesterol, 27-hydroxycholesterol, and the plant sterols campesterol, stigmasterol, and sitosterol were similar across control and patient groups. Notably, serum lathosterol was elevated in CD patients compared to those with UC, PSC, PSC-IBD, and healthy controls. All other serum and fecal sterols showed no differences between CD and UC. Cholesterol synthesis precursors in serum, serum cholesterol levels, and both serum and fecal plant sterol levels decreased with increasing IBD severity. Consequently, serum cholesterol, campesterol, sitosterol, and fecal 5-beta sitostanol and 5-alpha sitostanol were negatively correlated with C-reactive protein and fecal calprotectin. The conversion of cholesterol to coprostanol in feces was impaired in IBD, PSC, and PSC-IBD, independent of bowel inflammation severity or liver disease extent. Patients with PSC, and to a lesser extent PSC-IBD, had elevated serum plant sterol levels, positively correlating with liver disease markers. In conclusion, in patients with IBD, cholesterol biosynthetic precursors, serum cholesterol levels, and fecal plant sterols decrease with intestinal inflammation. An inverse association of serum plant sterols with intestinal inflammation was observed in patients with IBD and a direct association of serum phytosterols with liver injury in patients with PSC. The conversion of fecal cholesterol to coprostanol was impaired in all patient cohorts. IBD and PSC alter serum sterol levels differently, whereas changes in fecal sterols are not disease specific and are moderate.

Association of Hemogram Parameters with Body Mass Index in Knee Osteoarthritis

Objective: This study aims to investigate the relationship between hemogram parameters, which are low-cost, easy, routinely applied low-grade inflammation indicators, and severity of knee osteoarthritis (KOA) and obesity. Materials and Methods: This study involved 140 KOA patients aged 45 to 85 who underwent knee radiographs, weight and height measurements, and routine laboratory tests. Recorded data included demographic information (gender, age), body mass index (BMI), routine hemogram, and laboratory parameters. Patients were categorized into two groups based on their Kellgren-Lawrence (KL) scores (mild: KL 1-3, severe: KL 4) and four groups according to their BMI (BMI 35). Results: The findings revealed significantly elevated levels of serum Neutrophil-to-Lymphocyte Ratio (NLR) and C-reactive protein (CRP) in severe KOA compared to mild KOA (P30 in mild KOA groups, while mean blood NLR was notably higher in patients with BMI=30-35 in severe KOA groups. Conclusions: These results suggest that NLR and NMR could provide a new perspective on the relationship between obesity and mild KOA in clinical practice, presenting a cost-effective and easily applicable alternative for determining disease prognosis and progression.

Dexmedetomidine leads to the amelioration of stress response to surgery

Objectives: To determine the impact of intravenous Dexmedetomidine (Dex) administered perioperatively on stress response markers in patients undergoing ENT surgeries. Methods: This randomized interventional study was conducted at POFs Hospital and NUMS affiliated WMC, Wah Cantt, in collaboration with IIMC Rawalpindi, Pakistan, from October 2021 to April 2022. One hundred patients aged between 15-60 years, after satisfying the inclusion standards were randomly divided into two groups C and D. Group-C (n=50) received normal saline in addition to the standard anesthesia protocol. The intervention Group-D (n=50) was administered 1µg/kg dexmedetomidine hydrochloride intravenously over 10 minutes just before the induction followed 0.5μg/kg/hr as maintenance dose till the end of surgery. Serum inflammatory biomarkers (interleukins-6, TNF-α and cortisol) were measured in blood samples in both groups, taken at 0 (T0), 30 minutes(T1), and two hours (T2) time intervals and analyzed by using Enzyme-linked immunosorbent assay (ELISA). Data was statistically analyzed using SPSS 23. Results: The patients receiving Dex showed marked decrease in serum levels of cortisol, TNF- α and interleukins-6, from 139.73 to10.18, 99.51 to 0.96 and 85.09 to 0.96 respectively. Comparison between C and D groups revealed significant differences (p≤0.05) in these serum biomarkers. Conclusions: In the present study, intravenous Dex suppressed the intraoperative rise in levels of cytokine secretion and enhanced smooth recovery with no incidence of nausea and vomiting. These effects could be attributed to the anti-inflammatory effects of dexmedetomidine. Iranian Registry of Clinical Trials reference: IRCT20230824059251N1. Abbreviation:ENT: Ear, Nose and Throat, BMI: Body Mass Index, MAC: Monitored Cared Anesthesia, ASA: American Society of Anesthesiologists, SPSS: Statistical Package for Social Sciences, SD: Standard Deviation, PONV: Postoperative Nausea and Vomiting, OT: Operation Theater, POFs: Pakistan Ordinance Factories, WMC: Wah Medical College, IIMC: Islamic International Medical College, NUMS: National University of Medical Sciences. doi: https://doi.org/10.12669/pjms.40.9.8792 How to cite this: Ajmal K, Waheed A, Farooqi R, Mansoor Q. Dexmedetomidine leads to the amelioration of stress response to surgery. Pak J Med Sci. 2024;40(9):---------. doi: https://doi.org/10.12669/pjms.40.9.8792 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Lipocalin-2 as a marker of inflammation, bone density, and triglyceride-glucose index for new-onset arthritis patients in Mosul, Iraq.

Lipocalin-2 is an acute phase-associated adipokine that can serve as an inflammatory and biomarker indicator of cartilage deterioration in osteoarthritis. However, its role in the musculoskeletal system remains not fully understood. Hence, this study aimed to evaluate lipocalin-2 and its relationship with markers of inflammation (Interferon-gamma, ESR, and CRP), bone density (vitamin D3 and calcium), and the triglyceride-glucose index in new-onset arthritis patients in Mosul, Iraq. This study included 125 participants aged 20 to 65, divided into two groups. The Arthritis Patient Group comprised 70 participants (37 females and 33 males) attending the Bone Diseases Consultation Unit at the Ibn Sina Teaching Hospital in Mosul, Iraq. The Control Group comprised 31 females and 24 males. Ethical approval was obtained from the Iraqi Ministry of Health - Nineveh Health (No. 2022095). Commercial ELISA kits were used to measure serum lipocalin-2, Interferon-gamma, ESR, and CRP as inflammation markers, vitamin D3, and calcium as bone density markers. Moreover, the Triglyceride Glucose (TYG) Index was evaluated. The findings revealed a significant increase in lipocalin-2 levels in males compared to females, with LCN-2 increasing with age. Arthritis patients showed a significant increase (72%) in lipocalin-2 levels. Inflammatory indicators (erythrocyte sedimentation rate, C-reactive protein, interferon-gamma) displayed significant increases (46%, 1200%, and 581%, respectively). Glucose (23%), triglycerides (71%), and TYG index (21%) also exhibited significant increases. Meanwhile, bone density indicators (vitamin D3 and calcium) found a significant decrease (53% and 20%, respectively) in arthritis patients. Linear correlation coefficient (R) analysis revealed a significant positive relationship between lipocalin-2 and indicators of inflammation, glucose, TG, and TYG index. This study's findings suggest that LCN-2 serum levels were higher in patients with new-onset arthritis than in controls in Mosul, and LCN-2 serum increased in males compared with females and getting older serum LCN-2 increased for the patients and control groups. Furthermore, a significant correlation was found between the Triglyceride Glucose Index, which measures metabolic disorders, and serum LCN-2 levels and inflammatory indicators in new-onset arthritis patients in Mosul, Iraq.

Serum levels of iron, zinc, selenium, copper and oxidative stress in hypertensive patients: A comparative study of age-related changes in the governorate of Basrah, Iraq

Hypertension is the force of blood through blood vessels, where the heart works harder and blood vessels are under more pressure. The relationship between trace element levels and oxidative stress in hypertension is under investigation, with conflicting results. This study aimed to determine the relationship between concentrations of certain antioxidant trace elements (iron, zinc, selenium, and copper) and protein carbonyl concentration as an indicator of oxidative stress in the serum of hypertensive patients compared to the control group in Basra, Iraq, according to age. The study included 100 hypertensive patients (44 males and 56 females) compared to 50 healthy individuals (25 males and 25 females). Patients were divided into three age groups: 35–45, 46–56, and over 57 years. The study showed a significant decrease (p<0.001) in the mean concentration of all selected elements in the patients' serum compared to the control group. Conversely, the mean protein carbonyl level showed a significant increase (p<0.001) in patients compared to the control group. Trace element concentrations decreased in patients with increasing age, while carbonyl protein levels increased, especially in the third age group. The study also showed a significant negative correlation between protein carbonyl level and all trace elements at p<0.001. These results suggest that hypertension is associated with an imbalance in oxidative stress and trace elements. Monitoring trace element intake may help reduce oxidative stress and improve overall health in individuals with hypertension, especially with advancing age, by restoring the balance of essential elements and antioxidants in the body.

Cannabinoids Used for Medical Purposes in Children and Adolescents

Cannabinoids are increasingly used for medical purposes in children. Evidence of the safety of cannabinoids in this context is sparse, creating a need for reliable information to close this knowledge gap. To study the adverse event profile of cannabinoids used for medical purposes in children and adolescents. For this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched for randomized clinical trials published from database inception to March 1, 2024, for subject terms and keywords focused on cannabis and children and adolescents. Search results were restricted to human studies in French or English. Two reviewers independently performed the title, abstract, and full-text review, data extraction, and quality assessment. Included studies enrolled at least 1 individual 18 years or younger, had a natural or pharmaceutical cannabinoid used as an intervention to manage any medical condition, and had an active comparator or placebo. Two reviewers performed data extraction and quality assessment independently. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline and PRISMA-S guideline were used. Data were pooled using a random-effects model. The primary outcome was the incidence of withdrawals, withdrawals due to adverse events, overall adverse events, and serious adverse events in the cannabinoid and control arms. Secondary outcomes were the incidence of specific serious adverse events and adverse events based on organ system involvement. Of 39 175 citations, 23 RCTs with 3612 participants were included (635 [17.6%] female and 2071 [57.3%] male; data not available from 2 trials); 11 trials (47.8%) included children and adolescents only, and the other 12 trials (52.2%) included children, adolescents, and adults. Interventions included purified cannabidiol (11 [47.8%]), nabilone (4 [17.4%]), tetrahydrocannabinol (3 [13.0%]), cannabis herbal extract (3 [13.0%]), and dexanabinol (2 [8.7%]). The most common indications were epilepsy (9 [39.1%]) and chemotherapy-induced nausea and vomiting (7 [30.4%]). Compared with the control, cannabinoids were associated with an overall increased risk of adverse events (risk ratio [RR], 1.09; 95% CI, 1.02-1.16; I2 = 54%; 12 trials), withdrawals due to adverse events (RR, 3.07; 95% CI, 1.73-5.43; I2 = 0%; 14 trials), and serious adverse events (RR, 1.81; 95% CI, 1.21-2.71; I2 = 59%; 11 trials). Cannabinoid-associated adverse events with higher RRs were diarrhea (RR, 1.82; 95% CI, 1.30-2.54; I2 = 35%; 10 trials), increased serum levels of aspartate aminotransferase (RR, 5.69; 95% CI, 1.74-18.64; I2 = 0%; 5 trials) and alanine aminotransferase (RR, 5.67; 95% CI, 2.23-14.39; I2 = 0%; 6 trials), and somnolence (RR, 2.28; 95% CI, 1.83-2.85; I2 = 8%; 14 trials). In this systematic review and meta-analysis, cannabinoids used for medical purposes in children and adolescents in RCTs were associated with an increased risk of adverse events. The findings suggest that long-term safety studies, including those exploring cannabinoid-related drug interactions and tools that improve adverse event reporting, are needed.

Polymeric immunoglobulin receptor promotes Th2 immune response in the liver by increasing cholangiocytes derived IL-33: a diagnostic and therapeutic biomarker of biliary atresia

Biliary atresia (BA) is a devastating neonatal cholangiopathy with an unclear pathogenesis, and prompt diagnosis of BA is currently challenging. Proteomic and immunoassay analyses were performed with serum samples from 250 patients to find potential BA biomarkers. The expression features of polymeric immunoglobulin receptor (PIGR) were investigated using human biopsy samples, three different experimental mouse models, and cultured human biliary epithelial cells (BECs). Chemically modified small interfering RNA and adenovirus expression vector were applied for invivo silencing and overexpressing PIGR in a rotavirus-induced BA mouse model. Luminex-based multiplex cytokine assays and RNA sequencing were used to explore the molecular mechanism of PIGR involvement in the BA pathogenesis. Serum levels of PIGR, poliovirus receptor (PVR), and aldolase B (ALDOB) were increased in BA patients and accurately distinguished BA from infantile hepatitis syndrome (IHS). Combined PIGR and PVR analysis distinguished BA from IHS with an area under the receiver operating characteristic curve of 0.968 and an accuracy of 0.935. PIGR expression was upregulated in the biliary epithelium of BA patients; Th1 cytokines TNF-α and IFN-γ induced PIGR expression in BECs via activating NF-κB pathway. Silencing PIGR alleviated symptoms, reduced IL-33 expression, and restrained hepatic Th2 inflammation in BA mouse model; while overexpressing PIGR increased liver fibrosis and IL-33 expression, and boosted hepatic Th2 inflammation in BA mouse model. PIGR expression promotes the proliferation and epithelial-mesenchymal transition, and reduced the apoptosis of BECs. PIGR participated in BA pathogenesis by promoting hepatic Th2 inflammation via increasing cholangiocytes derived IL-33; PIGR has the value as a diagnostic and therapeutic biomarker of BA. This study was financially supported by the National Natural Science Foundation of China (82170529), the National Key R&D Program (2021YFC2701003), and the National Natural Science Foundation of China (82272022).

Relevance of antigen-induced IL-6 and mitogen-induced or spontaneous IFN-γ secretions in whole blood cultures for detection of Mycobacterium tuberculosis infection and disease.

For an effective control of tuberculosis (TB), there is a persistent need for biomarkers that can report true estimates of TB infection (TBI) and predict its progression towards active TB disease. We investigated whether the cell-mediated immune responses to Mycobacterium tuberculosis (Mtb) antigens could provide such biomarkers. The study subjects (n = 174) comprised a cohort of smear-positive, drug-sensitive, HIV-negative pulmonary TB patients (n = 54) and their household contacts (HC, n = 120). Whole blood cultures, in the presence or absence of Mtb antigens- membrane (MtM), purified protein derivative (PPD) and alpha-crystallin (Acr), or the mitogen PHA were subjected to determinations, by flow cytometry, for T cell proliferative and, by ELISA, for IFN-γ, TNF-α, and IL-6 cytokine responses. Additionally, serum levels of the three cytokines were also estimated. The strongest cell-proliferative and cytokine responses were induced by MtM and IL-6 was the most abundantly produced cytokine. While none of the responses induced by Mtb antigens or the serum cytokines levels could discriminate between TB and HC, the exvivo cytokine responses induced by PHA or 'spontaneously' could apparently do so. The concentrations of IFN-γ induced by PHA in TB blood cultures were significantly lower than in HC cultures (AUC = 0.72). Conversely, the spontaneous IFN-γ or TNF-α secretions in TB cultures were significantly higher than in HC cultures (AUC = 0.66). Our results suggest that IL-6 responses to MtM could be a sensitive indicator of TBI, and low levels of PHA-induced or high levels of spontaneous IFN-γ secretions in HC blood cultures may indicate a progressive infection.

No signs of mast cell involvement in long-COVID: Acase-control study.

Long-COVID caused by SARS-CoV-2 infection has significant and increasing effects on human health worldwide. Although a unifying molecular or biological explanation is lacking, several pathophysiological mechanisms have been proposed. Involvement of mast cells-evolutionary old "multipurpose" innate immune cells-was reported recently in studies of acute infection and post-acute-COVID-19 syndrome. Mast cell activity has been suggested in long-COVID. In this case-control study, we compared data from 24 individuals with long-COVID (according to the NICE criteria) and 24 age- and sex-matched healthy individuals with a history of SARS-CoV-2 infection without developing sequelae. Serum levels of the proteases beta-tryptase (TPSB2) and carboxypeptidase (CPA3), which are mast cell specific, were measured using immunoassays. The values were compared between the two groups and correlated to measures of physical exertional intolerance. TPSB2 and CPA3 levels were median (range) 26.9 (2.0-1000) and 5.8 (1.5-14.0) ng/mL, respectively, in the long-COVID group. The corresponding values in the control group were 10.9 (2.0-1000) (p = 0.93) and 5.3 (3.5-12.9) ng/mL (p = 0.82). No significant correlations between TPSB2 or CPA3 levels and scores on the ten physical subscales of SF-36, 3.1-3.10 were revealed. We found no significant differences in the levels of mast cell activation markers TPSB2 and CPA3 between the long-COVID and control groups and no correlations with proxy markers of exercise intolerance. Mast cell activation does not appear to be part of long-term pathogenesis of long-COVID, at least in the majority of patients.

Serum and Tissue CXCL9 Levels in Patients with Vitiligo Before and After Phototherapy: A Case-Control Study

Background: Vitiligo is a common pigmentation disease that affects 1–2% of the global population. It is a genetic disease that is triggered by an environmental factor resulting in an autoimmune disease. The predominance of the T-helper 1 (Th1) pattern favors the development of vitiligo. Interferon-gamma (IFN-γ) is the most important cytokine that is associated with the Th1 immune response. IFN-γ induces the release of chemokine which is called CXCL9. Objectives: Evaluation of the effects of narrow band ultraviolet B (nbUVB) phototherapy on the serum and tissue levels of CXCL9 among vitiligo patients. Patients and methods: We recruited in our study two groups; one group of twenty patients complaining of nonsegmental vitiligo and the other is a control group composed of another age and sex-matched twenty healthy controls, we assessed the serum level of CXCL9 in all subjects before the study and the patient group was reassessed after treatment with nbUVB for 12 weeks. We also determined tissue level of CXCL9 in patients before and after the phototherapy for 12 weeks from suction blister fluid. Results: We detected that serum levels of CXCL9 were higher in patients with vitiligo compared to healthy matched controls. nbUVB sessions for twelve weeks were done, and we found that serum and tissue levels of CXCL9 after treatment were decreased. Conclusion: Serum and tissue CXCL9 can be used as a marker for disease activity and potentiality for the response to treatment. Therefore, targeting the inhibition of the Interferon-γ-chemokine axis may help in treating the disease activity.

Serum and urinary levels of MIF, CD74, DDT and CXCR4 among patients with type 1 diabetes mellitus, type 2 diabetes and healthy individuals: Implications for further research

BackgroundMacrophage migration inhibitory factor (MIF) is a highly conserved cytokine with pleiotropic properties, mainly pro-inflammatory. MIF seems to exert its pro-inflammatory features by binding to its transmembrane cellular receptor CD74. MIF also has CXCR4, which acts as a co-receptor in this inflammatory process. Apart from MIF, D-dopachrome tautomerase (DDT) or MIF2, which belongs to the MIF superfamily, also binds to receptor CD74. Therefore, these molecules, MIF, CD74, DDT and CXCR4 are suggested to work together orchestrating an inflammatory process. Diabetes mellitus is characterised by chronic low-grade inflammation. Therefore, the aim of the present study was to evaluate serum and urinary levels of the aforementioned molecules among patients with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and among healthy controls. MethodsWe enrolled 13 patients with T1DM, 74 patients with T2DM and 25 healthy individuals as controls. Levels of CD74, CXCR4, DDT, and MIF were measured using ELISA Kits according to the manufacturer's instructions. ResultsWe documented increased serum MIF levels together with higher urinary CD74 levels among patients with T1DM, when compared to patients with T2DM and healthy adults. In particular, patients with T1DM showed significantly increased levels of MIF compared to T2DM (p = 0.011) and healthy controls (p = 0.0093). CD74 in urine were significantly higher in patients with T1DM compared to those affected with T2DM (p = 0.0302) and healthy group (p = 0.0099). On the contrary, serum CD74 were similar among the three groups. No statistical differences were identified in CXCR4 levels both in serum and in urine of all groups. Patients with T2DM and overweight/obesity had increased urinary levels of CD74, when compared to lean patients with T2DM. ConclusionThe increased serum MIF levels and urinary CD74 levels among patients with T1DM may be attributed to the autoimmune milieu, which characterises patients with T1DM, when compared to patients with T2DM. These two findings merit further attention as they could pave the way for further research regarding the potential beneficial effects of inhibitors of MIF among patients with T1DM, especially in the early stages of T1DM. Finally, the role of inhibitors of MIF could be further explored in the context of obesity among patients with T2DM.

Association between serum potassium, risk and prognosis of peritonitis in peritoneal dialysis patients-results from the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study.

Hypokalemia has been associatedwith an increased risk of peritoneal dialysis (PD)-associated peritonitis. However, hypokalemia is commonly associated with malnutrition, inflammation, and severe coexisting comorbidities, which thus are suspected of being potential confounders. This study was aimed at testingwhether hypokalemia was independently associated with the occurrence and prognosis of PD-associated peritonitis. A national-level dataset from the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study was used to explore the independent association of serum potassium with PD-associated peritonitis. Unmatched and propensity score-adjusted multivariate competing risk models, as well as univariate competing risk models following 1:1 propensity score matching, were conducted to balance potential biases between patients with and without hypokalemia. The association between potassium levels prior to peritonitis and treatment failure due to peritonitis was also investigated. During a median follow-up of 25.7months in 7220 PD patients, there was a higher incidence of peritonitis in patients with serum potassium below 4.0mmol/L compared to those withhigher serum levels (677 [0.114/patient-year] vs. 914 [0.096/patient-year], P = 0.001). After adjusting for demographics, laboratory tests, residual renal function, and medication use, baseline potassium levels below 4.0mmol/L were not linked to an increased risk of peritonitis, with a hazard ratio of 0.983 (95% CI 0.855-1.130, P = 0.810). This result remained consistent in both the propensity score adjusted multivariate competing risk regression (HR = 0.974, 95% CI 0.829-1.145, P = 0.750) and the univariate competing risk regression after 1:1 propensity score matching (Fine-Gray test, P = 0.218). The results were similar when analyzing patients with serum potassium level above or below 3.5mmol/L. Lastly, hypokalemia before the occurrence of peritonitis was not independently associated with treatment failure. Hypokalemia was not found to be an independent risk factor for PD-associated peritonitis or treatment failure of peritonitis in China.

Impact of oxaliplatin and trastuzumab combination therapy on tumor markers and T lymphocyte subsets for advanced gastric cancer

BACKGROUND Advanced gastric cancer (AGC) remains a challenging malignancy with poor prognosis. The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment. This study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment response. AIM To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with AGC. METHODS This prospective study enrolled 60 patients with AGC. All patients received oxaliplatin (130 mg/m2, every 3 weeks) and trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) for six cycles. Serum carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), and cancer antigen 72-4 (CA72-4) were measured before and after treatment. T-lymphocyte subsets, including CD3+, CD4+, CD8+, and CD4+ /CD8+ ratios, were also evaluated. The clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS After six cycles of treatment, the CEA, CA19-9, and CA72-4 serum levels significantly decreased compared to baseline levels (P < 0.001). The percentages of CD3+ and CD4+ T lymphocytes increased significantly (P < 0.05), whereas the percentage of CD8+ T lymphocytes decreased (P < 0.05). The CD4+/CD8+ ratio also significantly increased after treatment (P < 0.05). Patients with a higher decrease in serum tumor markers (≥ 50% reduction) and a higher increase in CD4+/CD8+ ratio (≥ 1.5-fold) showed better clinical response rates (P < 0.05). CONCLUSION Oxaliplatin and trastuzumab combination therapy effectively reduced serum tumor marker levels and modulated T lymphocyte subsets in patients with AGC. Combination therapy not only has a direct antitumor effect, but also enhances the immune response in patients with AGC. Serum tumor markers and T lymphocyte subsets may serve as potential predictive biomarkers for treatment response in patients with AGC receiving combination therapy.

Clinical significance of peripheral blood UL16 and DR-70 for the early diagnosis and prognostic evaluation of colorectal cancer

BACKGROUND Early diagnosis of colorectal cancer (CRC) is of great significance to improve the survival rate and quality of life of patients, but early diagnosis of CRC requires more sensitive techniques. Peripheral blood UL16-binding protein 2 (ULBP2) and human fibrinogen degradation products (DR-70) are the main indicators for the diagnosis of malignant tumors. AIM To assess ULBP2 and DR-70 potential for the early diagnosis and prognostic evaluation of CRC to provide a reference. METHODS This study involved 60 patients with early-stage CRC (CRC group), 50 patients with benign colorectal tumors (benign group), and 50 healthy patients (control group) enrolled at the Affiliated Hospital of Jiangnan University and Jiangsu Province Official Hospital between January, 2020 and January, 2022. ULBP2 and DR-70 levels in the blood were determined and differences among the three groups and early diagnostic values for CRC were determined. Patients with CRC were divided into the good prognosis and poor prognosis groups, and ULBP2 and DR-70 levels in the blood and diagnostic values were compared. RESULTS ULBP2 and DR-70 serum levels were significantly higher in the CRC group than in the control and benign groups (P < 0.05); however, no significant differences were observed between the benign and control groups (P > 0.05). Among the 60 patients with CRC followed up for two years, two died (3.33%) and 15 exhibited tumor metastasis, progression, or recurrence (25.00%). ULBP2 and DR-70 serum levels were significantly higher in the poor prognosis group than in the good prognosis group (P < 0.05). A receiver operating characteristic curve was plotted. Area under the curve, sensitivity, and specificity of serum ULBP2 with DR-70 for the early diagnosis of CRC were higher than those of the single serum indices (P < 0.05) in both the good and poor prognosis groups. CONCLUSION ULBP2 and DR-70 serum levels were significantly high in patients with early-stage CRC. They improved the diagnostic rate of early-stage CRC and predicted patient prognosis, thereby showing clinical application potential.

Fibroblast growth factor 21 improves insulin sensitivity by modulating the bile acid-gut microbiota axis in type Ⅱ diabetic mice

BackgroundFibroblast growth factor 21 (FGF21) is an important regulator of glycolipid metabolism. However, whether the gut microbiota is related to the anti-diabetic and obesity effects of FGF21 remains unclear. MethodsOur research used KO/KO db/db male mice and streptozotocin (STZ)-induced to simulate the construction of two type II diabetic mellitus (T2DM) models, and detected impaired glucose tolerance in the model by using the ipGTT and ITT assays, and collected feces from the model mice for sequencing of the intestinal flora and the content of short-chain fatty acids. H＆E staining was used to detect changes in intestinal tissue, the serum levels of LPS and GLP-1 were detected by ELISA. ResultsIn this study, we found that FGF21 significantly improved insulin sensitivity, attenuated intestinal lesions, and decreased serum lipopolysaccharide (LPS) concentrations in T2DM mice. Moreover, FGF21 reshaped the gut microbiota and altered their metabolic pathways in T2DM mice, promoting the production of short-chain fatty acids (SCFAs) and the secretion of glucagon-like peptide 1 (GLP-1). Fecal transplantation experiments further confirmed that feces from FGF21-treated diabetic mice demonstrated similar effects as FGF21 in terms of anti-diabetic activity and regulation of gut microbiota dysbiosis. Additionally, the antibiotic depletion of gut microbiota abolished the beneficial effects of FGF21, including increased GLP-1 secretion and fecal SCFA concentration. Additionally, the FGF21 effects of ameliorating intestinal damage and suppressing plasma LPS secretion were suppressed. All these findings suggest that FGF21 prevents intestinal lesions by modifying the gut microbiota composition. Furthermore, FGF21 affected bile acid synthesis by inhibiting CYP7A1, the key enzyme of bile acid synthesis. ConclussionTherefore, FGF21 enriched beneficial bacteria by preventing bile acid synthesis and stimulating the secretion of the intestinal hormone GLP-1 via the increased production of gut microbiota metabolites, thereby exerting its anti-diabetic effects.

Serum Level of S100B Protein as a Biomarker of Therapeutic Adherence in Parkinson’s Disease Patients

Pharmacological management of Parkinson’s disease (PD) is complex and may negatively impact patients' adherence to therapy. Several objective and subjective approaches are used to assess therapeutic adherence. Measurement of biological markers, that are well correlated with the effect of the medications, and that are distributed into easily accessible body fluids would be feasible approach for measuring therapeutic adherence for these medications. S100B protein has been proposed to be involved in the pathophysiology of PD. The study aims to measure the serum S100B level in PD patients and to assess its potentials to be used as a biomarker to predict therapeutic adherence in PD patients. Sixty-eight adult outpatients, of both genders, who were already diagnosed with PD, receiving different anti-Parkinson medications, were enrolled in this cross-sectional study. Hoehn and Yahr scale was used to determine the stage of disease; while, therapeutic adherence to treatment was assessed using the Arabic version of Morisky Medication Adherence Scale (MMAS-8). Serum S100B level was measured by enzyme-linked immune sorbent assay. Serum S100B level of participants was 10.55 (13.3) ng/l, and there was no significant difference between medians of S100B protein according to disease stages, P =0.975. Serum S100B level in patients with poor therapeutic adherence [14.2 (13.2) ng/l] was significantly higher than that in patients with good therapeutic adherence [3.14 (3.34)]; P = 0.008. Furthermore, serum S100B level with the MMAS-8; (r= -0.414, P = 0.001). Finally, at a cut-off point 3.57 ng/l and above, serum S100B level was shown to have good potential [area under the curve (AUC)= 0.715], as biomarker of therapeutic adherence with 70.6% sensitivity and 70.6%, specificity; P = 0.008. In conclusion, serum S100B level in PD patients is negatively correlated with therapeutic adherence level and has good potentials as biomarker of therapeutic adherence in PD patients to anti-Parkinson medications.

Association of apolipoprotein E gene polymorphism with gallstone disease in Iraqi Kurdish women

Gallstone disease (GSD) is a worldwide problem; the frequency of GSD varies greatly amongst different ethnic groups, possibly due to environmental and genetic factors. One circulating lipoprotein involved in lipid metabolism is apolipoprotein E (APOE). The APOE gene is polymorphic, has three distinct alleles, APOE2, APOE3, and APOE4. The an APOE polymorphism is linked to a variety of diseases, including Alzheimer's and type-two diabetes, so this study aimed to assess the relationship among various APOE genotypes and alleles with gallstone cases in Iraqi Kurdish women. The present case-control study involved 81 cases with laparoscopic cholecystectomy for gallstone disease and 80 healthy women without GSD. Genomic DNA samples were taken from blood to find the genotype of APOE using allele-specific sequence-primers and a method based on polymerase chain reaction (PCR). lipid profiles were examined using an automated biochemical analyzer. SPSS and GraphPad Prism 9.1.1 software were used to conduct the statistical analysis. No significant relationships were found between healthy people and GSD patients in genotype and allele frequencies. However, the genotype for E3/E4 and the APOE4 allele in GSD patients were higher than the controls (9.88% vs. 5.0% and 4.94% vs. 2.5%, respectively; P <0.05) but statistically nonsignificant. serum levels of cholesterol, low-density lipoproteins, and very low-density lipoproteins were higher, and the levels of serum high-density lipoprotein was lower than controls. These findings revealed no connection between the examined polymorphisms and gallstone cases. Additionally, it was demonstrated that gallstone disease and lipid parameters had a favorable relationship. Keywords: Apolipoprotein E, APOE, Gallstone disease, Genotype, Polymorphisms.