Serum Levels Research Articles

Futility of Up-Front Resection for Anatomically Resectable Pancreatic Cancer.

There are currently no clinically relevant criteria to predict a futile up-front pancreatectomy in patients with anatomically resectable pancreatic ductal adenocarcinoma. To develop a futility risk model using a multi-institutional database and provide unified criteria associated with a futility likelihood below a safety threshold of 20%. This retrospective study took place from January 2010 through December 2021 at 5 high- or very high-volume centers in Italy. Data were analyzed during April 2024. Participants included consecutive patients undergoing up-front pancreatectomy at the participating institutions. Standard management, per existing guidelines. The main outcome measure was the rate of futile pancreatectomy, defined as an operation resulting in patient death or disease recurrence within 6 months. Dichotomous criteria were constructed to maintain the futility likelihood below 20%, corresponding to the chance of not receiving postneoadjuvant resection from existing pooled data. This study included 1426 patients. The median age was 69 (interquartile range, 62-75) years, 759 patients were male (53.2%), and 1076 had head cancer (75.4%). The rate of adjuvant treatment receipt was 73.7%. For the model construction, the study sample was split into a derivation (n = 885) and a validation cohort (n = 541). The rate of futile pancreatectomy was 18.9% (19.2% in the development and 18.6% in the validation cohort). Preoperative variables associated with futile resection were American Society of Anesthesiologists class (95% CI for coefficients, 0.68-0.87), cancer antigen (CA) 19.9 serum levels (95% CI, for coefficients 0.05-0.75), and tumor size (95% CI for coefficients, 0.28-0.46). Three risk groups associated with an escalating likelihood of futile resection, worse pathological features, and worse outcomes were identified. Four discrete conditions (defined as CA 19.9 levels-adjusted-to-size criteria: tumor size less than 2 cm with CA 19.9 levels less than 1000 U/mL; tumor size less than 3 cm with CA 19.9 levels less than 500 U/mL; tumor size less than 4 cm with CA 19.9 levels less than 150 U/mL; and tumor size less than 5 cm with CA 19.9 levels less than 50 U/mL) were associated with a futility likelihood below 20%. Both disease-free survival and overall survival were significantly longer in patients fulfilling the criteria. In this study, a preoperative model (MetroPancreas) and dichotomous criteria to determine the risk of futile pancreatectomy were developed. This might help in selecting patients for up-front resection or neoadjuvant therapy.

Measuring serum and drainage fluid interleukin-6 and tumor necrosis factor-α levels for early detection of infectious complications after minimally invasive surgery for gastric cancer

ObjectiveInterleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are inflammatory cytokines produced in response to biological invasion or infection. Their levels are elevated in the blood and locally. We examined whether measuring IL-6 and TNF-α levels in serum or drainage fluid on postoperative day (POD) 1 could detect infectious complications after minimally invasive surgery for gastric cancer. MethodsThis cohort study included 205 consecutive patients who underwent laparoscopic or robot-assisted gastrectomy for gastric cancer between November 2020 and July 2023. We measured serum and drainage fluid IL-6 and TNF-α levels on POD 1 after gastrectomy. Receiver operating characteristic (ROC) curves were created to compare the diagnostic values of each cytokine and serum C-reactive protein levels for detecting postoperative infectious complications. ResultsIL-6 and TNF-α levels in the serum or drainage fluid were significantly higher in patients with an infectious complication. In addition, drainage fluid IL-6 levels were significantly different in patients with versus without intra-abdominal abscess. In the ROC curve analysis, serum and drainage fluid IL-6 had the highest AUC values for any infectious complication and intra-abdominal abscess, respectively. POD 1 serum IL-6 level above 47 pg/mL could detect any infectious complication with sensitivity of 74.1% and specificity of 71.8%. POD 1 drainage fluid IL-6 level above 14,750 pg/mL had 100% sensitivity for detecting intra-abdominal abscess with specificity of 56.0%. ConclusionsMeasurement of IL-6 levels in blood and drainage fluid on POD 1 is valuable for early detection of postoperative infectious complications or intra-abdominal abscess after gastric cancer surgery.

Dioscin attenuates lupus nephritis in NZB/W F1 mice by decreasing NF-κB activation and NLRP3 inflammasome.

. Dioscin, a natural steroid saponin, has anticancer, anti-inflammatory, anti-hyperlipidemic, and glycemic capabilities. This study focused on dioscin roles and its related mechanisms in experimental lupus nephritis. . Lupus-prone NZB/W F1 mice were intragastrically administered with dioscin, prednisone or vehicle, and kidney, urine and blood samples were harvested after the mice were sacrificed. Proteinuria, blood urea nitrogen (BUN), creatinine, anti-dsDNA, IL-1β, and IL-18 levels in serum as well as IFN-γ, IL-6, IL-17 and TNF-α levels in kidney tissues were assessed. Renal histopathology was examined through hematoxylin-eosin staining. IgG and C3 expression in kidney was evaluated using immunofluorescence staining. The number of glomerular F4/80-positive cells and NLRP3-positive cells was determined by immunohistochemical staining. The protein expression was examined by western blotting. . Dioscin alleviated lupus nephritis in NZB/W F1 mice. Dioscin declined serum anti-dsDNA level, prevented deposition of immune complexes in renal glomeruli, and inhibited the inflammatory response and infiltration of macrophages into mouse kidneys. Dioscin inhibited NF-κB and NLRP3 inflammasome in NZB/W F1 mice. . Dioscin ameliorates lupus nephritis through inhibition of NLRP3 inflammasome and NF-κB signaling.

Expression of miR-34a, RASSF1A and E-cadherin in relation to PRB in endometrioid carcinoma and its precursor.

The current study aims to evaluate the levels of miR-34a, RASSF1A, and E-cadherin in relation to the levels of isoform B of progesterone receptor (PRB) in endometrioid carcinoma (EC) and atypical hyperplasia (AEH) and their association with clinicopathological parameters. 105 cases (35 EC, 35 AEH, and 35 control) were involved in this study. Cases of AEH received treatment, and other samples were obtained after 6 months to assess the response. E-cadherin and PRB were assessed by immunohistochemistry (IHC), RASSFA methylation by MSP-PCR, and its serum level by ELISA and miR-34a via quantitative PCR. The expressions of miR-34a, RASSF1A, E-cadherin, and PRB differ among the studied groups; all were higher in normal compared with AEH and EC, with a statistically significant difference. The higher PRB expression and decreased miR-34a and RASSF1A expression were associated with resistance to hormonal therapy in AEH. High PRB in EC is associated with lower RASSFA1, E-cadherin, and miR-34a. Decreased expressions of RASSF1A, miR-34a, and E-cadherin had a significant connection to advanced stages. Expression of PRB and miR-34a and serum levels of RASSF1A predict response to treatment in cases of AEH. High PRB and low E-cadherin expression are associated with progressive disease in EC.

Correlation between matrix metalloproteinase-2, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinases-1 and white matter hyperintensities in patients with cerebral small vessel disease based on cranial magnetic resonance 3D imaging

ObjectiveThe objective of this study was to investigate the correlation between serum levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels and their ratios with the severity of white matter hyperintensities (WMHs) in patients with cerebral small vessel disease (CSVD). MethodsThis cross-sectional study was done on a prospective cohort of patients with CSVD. Qualitative and quantitative analyses of WMHs were performed using Fazekas grading and lesion prediction algorithm (LPA) methods. Biomarkers MMP-2, MMP-9, and TIMP-1 were measured to explore their correlation with the severity of WMHs. ResultsThe sample consisted of 144 patients with CSVD. There were 63 male and 81 female patients, with an average age of 67.604 ± 8.727 years. Among these, 58.33% presented with white matter hyperintensities at Fazekas grading level 1, with an average total template volume of WMHs of 4.305 mL. MMP-2 (P = 0.025), MMP-9 (P = 0.008), TIMP-1 (P = 0.026), and age (P = 0.007) were identified as independent correlates of WMHs based on Fazekas grading. Independent correlates of the total template volume of WMHs included MMP-2 (P = 0.023), TIMP-1 (P = 0.046), age (P = 0.047), systolic blood pressure (P = 0.047), and homocysteine (Hcy) (P = 0.014). In addition, age (P = 0.003; P < 0.001), interleukin-6 (IL-6) (P < 0.001; P = 0.044), Hcy (P < 0.001; P < 0.001), glycated hemoglobin (HbA1c) (P = 0.016; P = 0.043), and chronic kidney disease (P < 0.001; P < 0.001) were associated with both WMHs Fazekas grading and the total template volume of WMHs. ConclusionSerum levels of MMP-9, MMP-2, and TIMP-1 were independently associated with the Fazekas grading, while serum TIMP-1 and MMP-2 levels were independently related to the total template volume of WMHs. The association of TIMP-1 and MMP-2 with the severity of CSVD-related WMHs suggests their potential role as disease-related biomarkers. However, further research is required to uncover the specific mechanisms underlying these interactions.

Umbilical cord blood as a substitute for neonatal blood in measuring serum albumin and immunoglobulin G levels.

In this study, we investigated the clinical feasibility of using umbilical cord blood as an alternative to neonatal blood for measuring serum albumin and immunoglobulin G (IgG) levels in newborns, including preterm newborns. Serum levels of albumin and IgG were measured in cord and neonatal blood from singleton newborns. We analyzed correlations and systematic errors between cord and neonatal blood measurements, stratifying the results for very preterm newborns (VPNs) born at a gestational age of less than 32 weeks and non-VPNs born at a gestational age of 32 weeks or later. Among all 494 newborns (78 VPNs and 416 non-VPNs), serum albumin and IgG levels were determined for 95.7% and 88.7% of them, respectively. Strong correlations between cord and neonatal blood were observed for the serum albumin and IgG levels (rs = 0.864 and 0.966, respectively). Moreover, the measurement errors between cord and neonatal blood were small for all newborns (0.2g/dL and 65mg/dL, respectively). These findings were consistent with both VPNs and non-VPNs. Umbilical cord blood is a suitable substitute for neonatal blood in measuring serum albumin and IgG levels in newborns, even in premature newborns.

Maternal Placental Growth Factor (PlGF) levels, sonographic placental parameters, and outcomes of IVF pregnancies with and without embryo trophectoderm biopsy.

In vitro fertilization (IVF) is associated with abnormal trophoblast invasion and resultant decreased levels of circulating placental biomarkers such as placental growth factor (PlGF).Our objective was to evaluate maternal serum levels of second/third trimester PlGF, sonographic placental parameters, and clinical outcomes among IVF frozen embryo transfer (FET) pregnancies with and without embryo trophectoderm biopsy. This was a retrospective study of pregnant patients who conceived using a single frozen embryo transfer (FET) and gave birth between 30 January 2018 and 31 May 2021. We compared PlGF levels, sonographic placental parameters, and clinical outcomes between FET with biopsy and FET without biopsy groups. The median PlGF level was 614.5 pg/mL (IQR 406-1020) for FET pregnancies with biopsy, and 717.0 pg/mL (IQR 552-1215) for FET pregnancies without biopsy. The adjusted mean difference was 190.9 pg/mL lower in the FET biopsy group (95% CI, -410.6, 28.8; p = 0.088). There were no statistically significant differences in placental parameters or clinical pregnancy outcomes. This exploratory study demonstrated a possible trend toward lower maternal serum PlGF in the pregnancies conceived with FET using a biopsied embryo. Further investigation is warranted into the potential placental health effects of trophectoderm biopsy.

Ticlopidine protects Hepatic Ischemia-Reperfusion Injury via suppressing ferroptosis

Hepatic ischemia-reperfusion injury (IRI) is a major cause of liver damage during hepatic resection, transplantation, and other surgical procedures, often leading to graft failure and liver dysfunction. Recent studies have identified ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, as a key contributor to IRI. In this study, we investigated the protective effects of Ticlopidine, a thienopyridine compound and platelet aggregation inhibitor, on hepatic IRI. Using a C57BL/6J mouse model, we demonstrated that prophylactic Ticlopidine treatment significantly reduced necrotic and fibrotic areas in liver tissues, as well as serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST). Prussian Blue staining revealed that Ticlopidine pretreatment decreased iron accumulation in hepatic tissues, whereas markers of lipid peroxidation (malondialdehyde and 4-hydroxynonenal) and ferroptosis (PTGS2) were significantly downregulated. Additionally, Ticlopidine ameliorated inflammatory infiltration as indicated by reduced Gr-1 staining. In vitro, Ticlopidine dose-dependently inhibited ferroptosis induced by various inducers in liver cancer cell lines HUH7 and fibrosarcoma cells HT1080. The protective effects involved partial rescue of lipid peroxidation, significant reduction of ferrous iron levels, and strong protection against mitochondrial damage. These findings suggested that Ticlopidine acts as a broad-spectrum ferroptosis inhibitor, offering a promising therapeutic approach for protecting the liver against IRI.

"Inhibitory immune checkpoints predict 7-day, in-hospital and 1-year mortality of internal medicine patients admitted with bacterial sepsis".

Sepsis is a life-threatening syndrome with complex pathophysiology and great clinical heterogeneity which complicates the delivery of personalized therapies. Our goals were to demonstrate that some biomarkers identified as regulatory immune checkpoints in preclinical studies could 1)improve sepsis prognostication based on clinical variables and 2)guide the stratification of septic patients in subgroups with shared characteristics of immune response or survival outcomes. We assayed the soluble counterparts of 12 biomarkers of immune response in 113 internal medicine patients with bacterial sepsis. IL-1 receptor-associated kinase M (IRAK-M) exhibited the highest hazard ratios (HRs) for increased 7-day (1.94 [1.17-3.20]) and 30-day mortality (1.61 [1.14-2.28]). HRs of IRAK-M and Galectin-1 for predicting 1-year mortality were 1.52 (1.20-1.92) and 1.64 (1.13-2.36), respectively. A prognostic model including IRAK-M, Galectin-1, and clinical variables (Charlson Comorbidty Index, multiple source of sepsis, and SOFA score) had high discrimination for death at 7 days and 30 days (area under the curve 0.90 [0.82-0.99]) and 0.86 [0.79-0.94], respectively). Patients with elevated serum levels of IRAK-M and Galectin-1 had clinical traits of immune suppression and low survival rates. None of the 12 biomarkers were independent predictors of 2-year mortality. Two inhibitory immune checkpoint biomarkers (IRAK-M and Galectin-1) helped identify 3 distinct sepsis phenotypes with distinct prognoses. These biomarkers shed light on the interplay between immune dysfunction and prognosis in patients with bacterial sepsis and may prove to be useful prognostic markers, therapeutic targets, and biochemical markers for targeted enrollment in targeted therapeutic trials.

Potential therapeutic properties of broccoli extract and soy isoflavones on improvement endometriosis and involved oxidative parameters.

In Endometriosis is a gynecological disorder characterized by the growth of endometrial tissue outside the uterine cavity that is associated with chronic pelvic pain and subfertility. The purpose of the study was to investigate the effect of broccoli extract (BE) alone and in combination with soy isoflavones (SI) on endometrial implants in female rat. In this study, endometriosis was induced surgically in 40 mature female rats. The rats were divided into 5 groups that were treated by oral gavage for 6weeks with 0.5 mL of saline 0.9 %/day (control group), BE (3,000 mg/kg/day), SI (50 mg/kg/day), BE/soy isoflavones (BE 3000 mg/kg/day+soy isoflavones 50 mg/kg/day) and diphereline as a standard medication (3 mg/kg) intramuscularly. At the end of treatments, the volume and histopathology of the endometrial implants were compared among the 5 groups. The serum levels of oxidative parameters including superoxide dismutase (SOD), malondialdehyde (MDA) and tumor necrosis factor alpha (TNF-α) were also compared between the groups. The volume of the implants significantly decreased in diphereline group (p=0.002). The histopathological grade of endometrial implants in BE/SI and diphereline group were significantly decreased compared to the control group (p=0.001). The serum levels of SOD in BE group were enhanced significantly in comparison to the control group (p=0.034). BE in combination with SI decreased the growth and histopathologic grades of transplanted endometrial implants. These herbal compounds may have the potential therapeutic effect to be used as an alternative medication for the treatment of endometriosis.

Melatonin mitigated methotrexate-induced hepatotoxicity through interrelated biological processes.

Hepatotoxicity associated with methotrexate (MTX) is mainly due to disruption of redox balance and development of oxidative injury to hepatocytes. Melatonin (MLT) is a potent antioxidant and regulates wide range of biological functions, processes and utilized as adjuvant for number of medical applications. The current study investigated the mitigating effect of MLT on the MTX-induced hepatotoxicity. Adult male rats received MLT (25mg/kg, orally) for seven days flowed by single injection of MTX (20mg/kg, ip) then treat with MLT continued for additional 7days. The present result showed MLT treatment mitigated histopathological changes in the liver that associated with normalization of ALT and AST activity as well as bilirubin, albumin and alfa-fetoprotein levels in serum of MLT + MTX-treated rat to comparable control level. MLT treatment significantly reduced MDA content and myeloperoxidase activity while enhanced the activity of superoxide dismutase, catalase and glutathione content in the liver indicating the empowerment of the antioxidant status. Amelioration of MLT-induced oxidative stress resulted in a reduction in the inflammatory response due to antioxidant restoration and inhibited apoptosis indicated by downregulation of caspase-3 expression. The replenishment of antioxidant content powers the defense system of the hepatocytes. As a result, apoptosis is reduced which might be due to the ability of MLT protect DNA integrity thus maintaining hepatocyte functions and structure. Consequently, liver histology was protected. In summary, MLT modulates liver function and structure by orchestrating linked processes, including redox balance, inflammatory response, suppression of caspase-3, and DNA damage.

Unmet needs in autoimmune hepatitis: Results of the prospective multicentre European Reference Network Registry (R-LIVER).

The European Reference Network on Hepatological Diseases (ERN RARE-LIVER) launched the prospective, multicentre, quality-controlled R-LIVER registry on rare liver diseases. The aim of this study was to assess the presentation and outcome of autoimmune hepatitis (AIH) after 1 year of treatment. Data were prospectively collected at the time of diagnosis and after 6 and 12 months follow-up. Complete biochemical response (CBR) was defined as normalization of alanine aminotransferase (ALT) and immunoglobulin G (IgG) serum levels. A total of 231 patients from six European centres were included in the analysis. After 6 months of treatment 50% (106/212), and after 12 months 63% (131/210) of patients reached CBR with only 27% (56/211) achieving a steroid-free CBR within the first year. Overall, 16 different treatment regimens were administered. Change of treatment, mostly due to intolerance, occurred in 30.4% within the first 6 months. In multivariate analysis, younger age at diagnosis (odds ratio [OR] = 1.03 [95% confidence interval (CI) 1.01-1.05]; p = .007), severe fibrosis (OR .38 [95% .16-.89], p = .026) and change of treatment within the first 6 months (OR .40 [95% CI .2-.86]; p = .018) were associated with a lesser chance of ALT normalization at 12 months follow-up. The landscape of AIH treatment in Europe is highly heterogeneous, even between expert centres. The results from this first European multicentre prospective registry reveal several unmet needs, highlighted by the overall low rates of CBR and the frequent failure to withdraw corticosteroids.

Prevalence and risk factors of osteopenia and osteoporosis among postmenopausal women: A cross-sectional study from Jordan.

Our aim was to predict the prevalence of osteopenia and osteoporosis and their associated risk factors among postmenopausal women from Jordan. In this cross-sectional study, a total of 368 postmenopausal women were recruited from King Abdullah University Hospital (KAUH) in the North of Jordan between September 2022 and April 2023. Bone mineral density (BMD) was measured using a dual-energy X-ray absorptiometry scan. T-score was used for osteoporosis diagnosis in accordance with the International Society for Clinical Densitometry (ISCD) guidelines. Data about sociodemographic and lifestyle variables were collected using face-to-face interviews. Medical records were used to retrieve participants' BMD information. Predictors of osteoporosis were identified using logistic regression. Prevalence of osteoporosis was 40.5%, while 44.6% of participants were diagnosed with osteopenia. The lumbar spine had the highest frequency of osteoporosis (30.4%), while the left femoral neck had the highest prevalence of osteopenia (46.3%). Postmenopausal women's age (p-value=.024), and history of chronic diseases (p-value=.038) were significant factors associated with increased osteoporosis risk. Postmenopausal women from Jordan had high prevalence of osteoporosis and osteopenia. It is therefore necessary to target risk factors leading to osteoporosis and to improve patients' lifestyles through patient education. Healthcare systems should consider early screening approaches for osteoporosis at the age of menopause and thereafter. Supplements of calcium and vitamin D may be routinely considered for this age group depending on their serum levels.

The relationship between serum transglutaminase-2 levels and the severity of chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) is an immunological disease that is depicted by high prevalence and eminent burden for patients and society that is attributable to the arbitrary nature of symptoms and inconsistent tools for assessment of activity and severity. Transglutaminase-2 (TG2) is a posttranslational enzyme that is pervasively expressed in many cells and tissue types including mast cells. It has various biological functions, and its role in allergic disorders has been highlighted and delineated through several postulated mechanisms. This case–control study aimed at determining the relationship between serum levels TG2 and severity of CSU. To the best of our knowledge, this is the first study in Egypt to determine the relationship between serum TG2 and severity of CSU. We enrolled 60 adult patients with confirmed diagnosis of CSU. According to urticaria activity score (UAS), patients were categorized into three groups [20 with mild disease; UAS = 0, 20 with moderate disease; UAS = 1–3, 20 with severe disease; UAS = 4–6]. Another 20 healthy individuals (age and gender matched) served as a control group. All patients were subjected to detailed medical history, clinical examination, complete blood count with differential, serum total IgE, CRP, ESR, TSH, ANA, liver and renal function tests. Serum level of TG2 was done by quantitative ELISA for all enrolled patients and controls. Serum TG2 is significantly higher in patients group compared to control group (P value < 0.001). Serum TG2 levels were significantly higher in patients with severe disease compared to patients with moderate or mild disease. This is illustrated by the significant positive correlation between serum TG2 and UAS (r 0.814 and P value 0.000). Moreover, serum TG2 accurately classified CSU patients into mild, moderate and severe subgroups: as regards differentiation between mild and moderate cases (sensitivity 70%, specificity 80%, PPV 77.8, NPV 72.7) and as for the differentiation between moderate and severe cases (sensitivity 95%, specificity 90%, PPV 90.5, NPV 94.7). Serum TG2 may have a pivotal role as a marker of severity in patients with CSU.

Obesity is associated with increased 11-oxyandrogen serum concentrations during puberty.

While the influence of various factors on classical androgen synthesis in children and adolescents and its impact on puberty has been widely investigated, there appear to be gaps and contradictory findings regarding the association of overweight and obesity with the synthesis of adrenal-derived 11-oxygenated androgen (11-OA) serum levels. With this study, we aimed to examine how overweight and obesity affect 11-OA serum levels during puberty in a large cohort of children and adolescents. Our cohort comprised 1,054 healthy children aged 6 to 19 years providing serum samples at a total of 1,734 visits. Liquid chromatography-tandem mass spectrometry was used to quantify 11-ketotestosterone (11-KT), 11-ketoandrostendione (11-KA4), 11-ß-hydroxytestosterone (11-OHT), 11-ß-hydroxyandrostendione (11-OHA4), testosterone, androstenedione, and DHEAS. In addition, we assessed BMI-SDSs; skinfold thicknesses; and Tanner stages. The significance level α was set to α=0.05. Increases in 11-KT, 11-KA4, 11-OHT, and 11-OHA4 levels were observed in boys and girls during puberty. 11-KT (ß=0.2, p&lt;0.001), 11-KA4 (ß=0.16, p&lt;0.001) and 11-OHA4 (ß=0.12, p=0.003) were positively correlated with BMI in boys age 13 and under. 11-KT (ß=0.1, p=0.047) was positively correlated with BMI in girls age 11 and under. 11-OHT was positively correlated with BMI independent of age (boys 13 and under: ß=0.17, p&lt;0.001; over 13 years: ß=0.14, p=0.001; girls 11 and under: ß=0.17, p&lt;0.001; over 11 years: ß=0.18, p&lt;0.001). We found increasing 11-OA serum levels throughout all Tanner stages. 11-OAs were observed to be associated with BMI and skinfold thickness, suggesting that overweight and obesity may be associated with pubertal alterations in 11-OA serum levels.

CXCL12/CXCR4 as a potential axis in diagnosis and predicting disease severity in COVID-19 patients: a new perspective

Abstract Objectives Coronavirus disease 2019 (COVID-19) exhibits variations in terms of patients’ clinical symptoms and levels of routinely employed biochemical markers. The aim of the current study was to determine the correlation between serum levels of the C-X-C chemokine ligand type 12 (CXCL12) and C-X-C chemokine receptor type 4 (CXCR4), one of its specific receptors, and disease severity in COVID-19 patients. Methods Sixty-nine patients were diagnosed with COVID-19 from February to July 2021, and a healthy control group of 39 individuals were enrolled in the study. Patients were divided into subgroups: mild-moderate and severe. Serum CXCL12 and CXCR4 levels were measured using the enzyme-linked immunosorbent assay method. Results CXCL12 and CXCR4 concentrations were both significantly higher in the clinically severe disease group compared to the mild-moderate disease group (p&lt;0.05 in both groups). CXCL12 and CXCR4 levels were also significantly higher in the patients with clinically mild-moderate disease compared to the control group (p&lt;0.001 and p&lt;0.05, respectively). Both CXCL12 and CXCR4 levels were correlated with clinical severity. Serum CXCL12 and CXCR4 levels were significantly positively correlated. Assuming a cut-off value of 1.44 ng/mL, serum CXCL12 levels showed 98 % sensitivity and 84 % specificity to distinguish between COVID-19 patients and healthy individuals (AUC=0.98, p&lt;0.001, 95 % CI=0.95–1.0). Serum CXCR4 levels distinguished individuals with COVID-19 from healthy controls with 88 % sensitivity and 72 % specificity at a cut-off value of 69.7 pg/mL (AUC=0.82, p&lt;0.001, 95 % CI=0.74–0.9). Conclusions Serum CXCL12 and CXCR4 levels may be included among the biomarkers used to differentiate patients with COVID-19 and determine the clinical severity of the disease.

Prophylactic Effects of Methanolic Leaf Extract of Momordica balsamina Against CCL4 Induced Liver Injury in Wistar Rats

Introduction: Liver injury can result from various causes, including alcohol consumption, viral infections (such as hepatitis), autoimmune diseases, metabolic disorders, and exposure to certain chemicals, drugs or toxins. It can manifest as inflammation, fatty liver disease, cirrhosis, or acute liver failure, depending on the cause and severity. Treatment often involves addressing the underlying cause, lifestyle changes (such as avoiding alcohol or certain medications), and sometimes medication to support liver function or manage specific conditions. Early detection and management are crucial for preventing further damage and promoting liver health. Studies have reported the effects of Momordica balsamina on liver injury. Aim: This study aim to evaluate the prophylactic effect of methanolic leaf extract of Momordica balsamina against CCL4-induced liver injury in Wistar Rats. Methodology: The fresh leaves of Momordica balsamina were purchased at Marina Market, Sokoto, the plant was air dry at room temperature for 2 weeks and the air-dried leaves were processed with methanol to obtain methanolic extract. An acute toxicity study of M. balsamina extract was conducted with six doses (10, 100, 1000, 1600, 2900 and 5000 mg/kg) to evaluate its safety. Phytochemical analysis of the extract was carried out to detect the presence or absence of carbohydrates, saponins, flavonoids, tannins, phenols, protein, alkaloids, cardiac glycosides and steroids. A total of 42 Wistar rats (170±20g) of either sex roughly of the same age (8-10 weeks) were used for the study. After two weeks of acclimatization, the rats were randomly divided into six groups of seven rats each; group 1 (normal control) treated with distilled water and vital feeds; groups 2 (Negative control) CCl4 treated with liver injury not on treatment; group 3 (Standard control) CCl4 liver injury treated with 50 mg/kg Silymarin; group 4 (500 mg/kg M. balsamina + 2mL CCl4); group 5 (1000 mg/kg M. balsamina + 2mL CCl4) and group 6 (1500 mg/kg M. balsamina + 2mL CCl4) for 4 weeks. On the last day, the rats were anaesthetized, and blood and liver organ were collected for biochemical and histomorphology study. Results: The prophylactic effects of methanolic leaf extract of Momordica balsamina against CCl4-induced liver injury were evaluated on liver function tests (LFTs) and Malondialdehyde (MDA). This study shows that Momordica balsamina extract significantly (P&lt; 0.05) decreased the level of serum AST, ALT, ALP, TB and DB positively by inhibiting their raise at dose-dependent manner compared to the negative control, equally, the extract increased the serum level of Albumin and total protein when compared to the negative control. On the other hand, the extract shows significant reduction of serum level of Malondialdehyde (MDA) near to normal at varying dose. The finding of the prophylactic effect of methanolic leaf extract of Momordica balsamina on histology shows significant improvement on liver cell with notable recovery and appearance of the histological architecture of the hepatocyte at the highest dose (1500 mg/kg+2mL CCl4) compared to negative control group. Conclusion: The presence of phytochemical compounds and antioxidant properties as well as a gene that is responsible for its prophylactic effect may be one of the mechanisms through which the plant extract was able to exert prophylactic effect on CCl4 induced liver injury in Wistar rats. This study suggests that M. balsamina extract may be considered as an affordable and non-invasive treatment option for liver injury in human.

Qing Hua Chang Yin ameliorates chronic colitis in mice by inhibiting PERK–ATF4–CHOP pathway of ER stress and the NF-κB signalling pathway

Context Ulcerative colitis has been clinically treated with Qing Hua Chang Yin (QHCY), a traditional Chinese medicine formula. However, its precise mechanisms in mitigating chronic colitis are largely uncharted. Objective To elucidate the therapeutic efficiency of QHCY on chronic colitis and explore its underlying molecular mechanisms. Materials and methods A total ion chromatogram fingerprint of QHCY was analysed. Chronic colitis was induced in male C57BL/6 mice using 2% dextran sodium sulphate (DSS) over 49 days. Mice were divided into control, DSS, DSS + QHCY (0.8, 1.6 and 3.2 g/kg/d dose, respectively) and DSS + mesalazine (0.2 g/kg/d) groups (n = 6). Mice were intragastrically administered QHCY or mesalazine for 49 days. The changes of disease activity index (DAI), colon length, colon histomorphology and serum pro-inflammatory factors in mice were observed. RNA sequencing was utilized to identify the differentially expressed transcripts (DETs) in colonic tissues and the associated signalling pathways. The expression of endoplasmic reticulum (ER) stress-related protein and NF-κB signalling pathway-related proteins in colonic tissues was detected by immunohistochemistry staining. Results Forty-seven compounds were identified in QHCY. Compared with the DSS group, QHCY significantly improved symptoms of chronic colitis like DAI increase, weight loss, colon shortening and histological damage. It notably reduced serum levels of IL-6, IL-1β and TNF-α. QHCY suppressed the activation of PERK–ATF4–CHOP pathway of ER stress and NF-κB signalling pathways in colonic tissues. Discussion and conclusions The findings in this study provide novel insights into the potential of QHCY in treating chronic colitis patients.

Effect of bariatric surgery in the body burden of persistent and non-persistent pollutants: longitudinal study in a cohort of morbidly obese patients

IntroductionObesity is a pathological state that involves the dysregulation of different metabolic pathways and adipose tissue cells, constituting a risk factor for the development of other diseases. Bariatric surgery is the most effective treatment. The study of the behavior of pollutants in situations of extreme weight loss can provide biomonitoring information and tools to manage diseases of environmental etiology.AimTo determine the prevalence of serum persistent and non-persistent pollutants in obese patients subjected to bariatric surgery and analyze the impact of sociodemographic variables on these changes.MethodsGC-MS/MS and UHPLC-MS/MS were utilized to determine the detection rates and concentrations of 353 compounds, including persistent organic pollutants (POPs), pesticides, pharmaceuticals, and rodenticide, in serum samples of 59 obese patients before and after undergoing bariatric surgery.ResultsDetection rates of p,p’-DDE, HCB, β-HCH, naphthalene, phenanthrene and PCB congeners 138, 153 and 180 significantly increased due to surgery-induced weight loss. Serum levels of p,p’-DDE, PCB-138, PCB-153 and PCB-180 also increased after surgery. Correlations between naphthalene levels, weight loss, variation of total lipids and time after surgery were found. Additionally, correlations were observed between concentrations of PCB-138 and weight loss, and between phenanthrene levels and reduction of total lipids. No statistically significant differences were observed for other groups of contaminants, pharmaceuticals and other chemicals included in the quantification methods.ConclusionsIncrement of POPs was observed after bariatric surgery. Serum concentrations of POPs after surgery were influenced by adiposity-related variables. Although biomonitoring studies show a decreasing tendency of exposure, rapid weight loss leads to an increase of circulating POPs. Further research on the interplay between adipose tissue, POPs and peripheral organs is required.

The Evaluation of Post-COVID-19 Effects on Ovarian Reserve and Menstruation in Reproductive-Aged Women in 2022: A Single-Centered Observational Study

Background: Despite the finite reproductive lifespan of women, the effect of Coronavirus disease 2019 (COVID-19) on female fertility is not widely evaluated, especially in the post-COVID recovery period. Objectives: The study aimed to detect COVID-19's long-term impact on ovarian reserve and menstruation in reproductive-aged women. Methods: One hundred and three reproductive-age women were recruited for this observational study from March to September 2022. Participants with a history of severe COVID-19 were included in the case group (n = 50), while those with non-severe or no infection were considered the control group (n = 53). The ovarian reserve was assessed using anti-Müllerian hormone (AMH) levels, and a structured questionnaire was used to evaluate menstrual cycle abnormalities. Results: We detected a significant decrease in the ovarian reserve indicator, AMH serum levels, in women with severe infection compared to controls (2.66 ± 1.95 vs. 3.38 ± 2.59 ng/L P = 0.03) in the post-COVID-19 recovery period. Characteristics related to menstrual cycle length and volume abnormalities, such as hypermenorrhea and hypomenorrhea, were similar in cases and controls (P = 0.79, P = 0.64), but the severity of dysmenorrhea was significantly higher in cases than controls (P = 0.02). Menstrual pain perception was not related to women’s marital status (r = 0.10, P = 0.27), employment (r = 0.16, P = 0.10), education (r = 0.11, P = 0.24), or AMH serum levels (r = 0.03, P = 0.74). Conclusions: This investigation sheds light on the potential long-term effects of severe COVID-19 on the ovarian reserve and menstrual cycle, which may lead to changes in female reproductive physiology. Longitudinal studies with larger sample sizes are needed to confirm the long-lasting fertility issues in women affected by severe COVID-19.