Serum Levels Research Articles

Serum proteomic analysis uncovers novel serum biomarkers for depression.

The identification of depression primarily relies on the clinical symptoms and psychiatric evaluation of the patient, in the absence of objective and quantifiable biomarkers within clinical settings. This study aimed to explore potential serum biomarkers associated with depression. Serum samples from a training group comprising 48 depression patients and 48 healthy controls underwent proteomic analysis. Magnetic bead-based weak cation exchange (MB-WCX) and MALDI-TOF-MS were used in combination. To screen the differential peaks, ClinProTools software was employed. The proteins were identified using LC-MS/MS. ELISA was employed to confirm the expression of entire protein in the serum of the verification cohort, which encompassed 48 individuals who had been diagnosed with Depression and 48 healthy controls who were collected prospectively. Subsequently, logistic regression analysis was conducted to determine the diagnostic efficacy of the aforementioned predictors. Five potential biomarker peaks indicating depression were identified in serum samples (peak 1, m/z: 1868.21; peak 2, m/z: 1062.35; peak 3, m/z: 1452.12; peak 4, m/z: 1208.72; peak 5, m/z: 1619.58). All of these peaks had higher expression in the pre-therapy group and were confirmed to be Tubulin beta chain (TUBB), Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), Complement component 3 (C3), and Complement C4A precursor (C4A) by ELISA validation. Multivariate logistic regression analysis revealed that serum levels of TUBB, ITIH4, C3, and C4A were significant independent risk factors for the development of depression. Depression is a prevalent psychiatric condition. Timely detection is challenging, resulting in poor prognoses for patients. Our study on plasma proteomics for depression demonstrated that TUBB, ITIH4, C3, and C4A differentiate between depression patients and healthy controls. The proteins that were identified could potentially function as biomarkers for the diagnosis of depression. Pinpointing these biomarkers could enable early identification of depression, which would advance precise treatment.

Protective effect of melatonin against metabolic disorders and neuropsychiatric injuries in type 2 diabetes mellitus mice

BackgroundType 2 diabetes mellitus (T2DM) is a metabolic disease characterized by hyperglycemia and progressive cognitive dysfunction, and our clinical investigation revealed that the plasma concentration of melatonin (Mlt) decreased and was closely related to cognition in T2DM patients. However, although many studies have suggested that Mlt has a certain protective effect on glucose and lipid metabolism disorders and neuropsychiatric injury, the underlying mechanism of Mlt against T2DM-related metabolic and cognitive impairments remains unclear. PurposeThe aim of the present study was to investigate the therapeutic effect of Mlt on metabolic disorders and Alzheimer's disease (AD)-like neuropsychiatric injuries in T2DM mice and to explore the possible underlying molecular mechanism involved. MethodsA T2DM mouse model was established by a combination of a high-fat diet (HFD) and streptozotocin (STZ, 100 mg/kg, i.p.), and Mlt (5, 10 or 20 mg/kg) was intragastrically administered for six consecutive weeks. The serum levels of glycolipid metabolism indicators were measured, behavioral performance was tested, and the protein expression of key molecules involved in the regulation of synaptic plasticity, circadian rhythms, and neuroinflammation in the hippocampus was detected. Moreover, the fluorescence intensities of glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule 1 (IBA-1), amyloid β-protein (Aβ) and phosphorylated Tau (p-Tau) in the hippocampus were also observed. ResultsTreatment with Mlt not only improved T2DM-related metabolic disorders, as indicated by increased serum concentrations of fasting blood glucose (FBG), glycosylated hemoglobin (HbAlc), insulin (INS), total cholesterol (TC) and triglyceride (TG), improved glucose tolerance and liver and pancreas function but also alleviated AD-like neuropsychiatric injuries in a HFD/STZ-induced mouse model, as indicated by decreased immobility time in the tail suspension test (TST) and forced swimming test (FST), increased preference indices of novel objects or novel arms in the novel object recognition test (NOR) and Y-maze test (Y-maze), and improved platform positioning capability in the Morris water maze (MWM) test. Moreover, treatment with Mlt also improved the hyperactivation of astrocytes and microglia in the hippocampus of mice, accompanied by reduced expression of interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor (TNF-α), Aβ, and p-Tau and increased expression of brain-derived neurotrophic factor (BDNF), Synapsin I, Synaptotagmin I, melatonin receptor 1B (MT1B), brain muscle arnt-like protein 1 (Bmal1), circadian locomotor output cycles kaput (Clock), period 2 (Per2), and cryptochrome 2 (Cry2). ConclusionMlt alleviated T2DM-related metabolic disorders and AD-like neuropsychiatric injuries in a HFD/STZ-induced mouse model, possibly through a mechanism involving the regulation of glial activation and associated neuroinflammation and the balancing of synaptic plasticity and circadian rhythms in the hippocampus.

Evaluation of the clinical application value of cytokine expression profiles in the differential diagnosis of prostate cancer

BackgroundThe significance of tumor-secreted cytokines in tumor development has gained substantial attention. Nevertheless, the precise role of tumor-related inflammatory cytokines in prostate cancer (PCa) remains ambiguous.ObjectivesTo gain deeper insights into the inflammatory response in the process of PCa.MethodsA total of 233 cases were collected, including 80 cases of prostate hyperplasia as disease control, 65 cases of postoperative prostate cancer and 36 cases of prostate cancer as PCa group. Additionally, 52 patients undergoing physical examinations during the same period were collected as the healthy control. The levels of 12 inflammatory cytokines in peripheral blood samples were analyzed using flow cytometric bead array technology. The levels of total prostate-specific antigen (TPSA) and free prostate-specific antigen (FPSA) in peripheral blood samples were analyzed using electrochemiluminescence technology.ResultsOur findings revealed significant increases in serum IL-8 levels in PCa group compared to the healthy control group. Additionally, IL-6, IL-10, IFN-γ and IL-12p70 levels were markedly elevated in the PCa group compared to the disease control group (all p < 0.05). Conversely, the level of IL-4, TNF-α, IL-1β, IL-17A and IFN-α were lower in the PCa group compared to those in control group. Following surgery, the concentration of IL-6 decreased; whereas, the concentrations of IL-4, TNF-α, IL-17A, IL-1β, IL-12p70, and IFN-α increased, demonstrating significant differences (p < 0.05). The differential upregulation of IL-6 or downregulation of IL-17A in peripheral blood exhibited diagnostic efficacy in PCa patients. Moreover, we observed a significant increase in IL-17A levels, accompanied by decreased of IL-2, IL-4, IL-10, TNF-a, IFN-γ, IL-1β, and IL-12P70 in patients with distant metastasis.ConclusionThe peripheral blood cytokines are closely associated with the occurrence and development of prostate cancer, especially the serum levels of IL-6 and IL-17A may be useful as potential predictors of PCa diagnosis.

Contributing to the management of viral infections through simple immunosensing of the arachidonic acid serum level

A trendsetting direct competitive-based biosensing tool has been developed and implemented for the determination of the polyunsaturated fatty acid arachidonic acid (ARA), a highly significant biological regulator with decisive roles in viral infections. The designed methodology involves a competitive reaction between the target endogenous ARA and a biotin-ARA competitor for the recognition sites of anti-ARA antibodies covalently attached to the surface of carboxylic acid-coated magnetic microbeads (HOOC-MµBs), followed by the enzymatic label of the biotin-ARA residues with streptavidin-horseradish peroxidase (Strep-HRP) conjugate. The resulting bioconjugates were magnetically trapped onto the sensing surface of disposable screen-printed carbon transducers (SPCEs) to monitor the extent of the biorecognition reaction through amperometry. The operational functioning of the exhaustively optimized and characterized immunosensing bioplatform was highly convenient for the quantitative determination of ARA in serum samples from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2-) and respiratory syncytial virus (RSV)-infected individuals in a rapid, affordable, trustful, and sensitive manner.Graphical

Monomeric C-reactive protein is associated with severity and prognosis of decompensated hepatitis B cirrhosis.

C-reactive protein (CRP) is an acute-phase protein produced by the liver in response to infection and during chronic inflammatory disorders. Systemic inflammation is a major driver of cirrhosis progression from the compensated to the decompensated stage. Previous studies have shown that pentameric CRP (pCRP) to be a weak predictor of disease severity and prognosis in patients with decompensated hepatitis B cirrhosis, with it being only helpful for identifying patients with a higher short-term risk of death under certain conditions. Accumulating evidence indicates that pCRP dissociates to and acts primarily as the monomeric conformation (mCRP) at inflammatory loci, suggesting that mCRP may be a potentially superior disease marker with higher specificity and relevance to pathogenesis. However, it is unknown whether mCRP and anti-mCRP autoantibodies are associated with disease severity, or progression in decompensated hepatitis B cirrhosis. In this study, we evaluated the serum levels of mCRP and anti-mCRP autoantibodies in patients with decompensated cirrhosis of hepatitis B and their association with disease severity and theoretical prognosis. The results showed that patients with high mCRP and anti-mCRP autoantibody levels had more severe liver damage and that coagulation function was worse in patients with high anti-mCRP autoantibodies. Analysis of the correlation between pCRP, mCRP and anti-mCRP autoantibody levels with Model for End-Stage Liver Disease (MELD), Albumin-Bilirubin (ALBI), and Child-Turcotte-Pugh (CTP) prognostic scores showed that mCRP was the most strongly correlated with MELD score, followed by anti-mCRP autoantibodies; conversely, pCRP was not significantly correlated with prognostic score. Therefore, mCRP and anti-mCRP autoantibodies may be more advantageous clinical indicators than pCRP for evaluating the pathological state of decompensated hepatitis B cirrhosis.

Serum S1P level in interstitial lung disease (ILD) is a potential biomarker reflecting the severity of pulmonary function

Backgroundsphingosine-1-phosphate (S1P), a naturally occurring sphingolipid, has been involved in pulmonary interstitial remodeling signaling. However, no study has examined its clinical merits for interstitial lung disease (ILD). This study aimed to investigate the serum level of S1P in ILD patients and its clinical correlation with the severity of disease in the two main types of ILDs: the IPF and the CTD-ILD patients.MethodsThis retrospective observational pilot study included 67 ILD patients and 26 healthy controls. These patients were stratified into the IPF group (35) and the CTD-ILD group (32). The severity of ILD was evaluated through pulmonary function indicators and the length of hospital stay.ResultsSerum S1P level was statistically higher in ILD patients than in health control (p = 0.002), while the Serum S1P levels in CTD-ILD and IPF patients were comparable. Serum S1P level further showed statistically negative correlation with pulmonary function indexes (TLC% pred, FVC% pred and FEV1% pred) and positive correlation with length of hospital stay (r = -0.38, p = 0.04; r = -0.41, p = 0.02, r = -0.37, p = 0.04; r = 0.42, p = 0.02, respectively) in CTD-ILD patients, although serum S1P level was not significantly correlated with inflammatory indexes. The IPF patients failed to exhibit a significant correlation of serum S1P level with pulmonary function and length of hospital stay.ConclusionsSerum S1P level might be a clinically useful biomarker in evaluating the severity of CTD-ILD patients rather than IPF patients.

Serum Visfatin Level in Psoriasis Patients: A Case-Control Study

Background Adipokines play imperative roles in the pathogenesis of psoriasis. Among the adipokines, visfatin is attracting more attention in the clinical setting of dermatology. Objective The study aims to evaluate the serum visfatin level in psoriasis patients compared to the non-psoriasis individuals. Material and Methods This case-control study involved 40 psoriasis patients and 40 non-psoriasis individuals from January to October, 2023, at the Ho Chi Minh City (HCMC) Hospital of Dermato-Venereology. The diagnosis of psoriasis was based on clinical signs and symptoms. Visfatin level was spectrophotometrically measured using an Enzym-Linked Immunosorbent Assay (ELISA) kit. Afterward, data analysis was performed using SPSS version 25. Results We recorded a significantly higher visfatin level in the psoriasis group than the controls (49.8 ± 26.04 versus 13.07 ±12.44, p-value &lt;0.001). The cut-off threshold of visfatin level to differentiate psoriasis from non-psoriasis was 21.7 ng/ml with a sensitivity of 90% and a specificity of 85% (AUC = 0.929). We also found a positive correlation between visfatin level and Psoriasis Area and Severity Index (PASI) score (r = 0.704; p &lt;0.001). Conclusion Our study indicated the link between serum level of visfatin and psoriasis. Visfatin is a potential biomarker in diagnosing psoriasis and classifying the disease’s severity. In further cohort studies and clinical trials, the adipokine can be validated for its use in psoriasis.

Cognitive profile in Egyptian multiple sclerosis patients has no correlation with serum neurofilament level

BackgroundGrey matter loss is thought to be the primary reason of cognitive disability in MS, with trans-synaptic axonal degeneration acting a supportive role. This research sought to evaluate cognitive profile of Egyptian multiple sclerosis patients and find out if it has a correlation with serum neurofilament or not.MethodsThis was a cross-sectional research performed on a total of 60 patients with MS and 30 healthy controls. BICAMS battery of neuropsychological tests was used which includes SDMT, CVLT and BVMT. Serum NFLs using ELISA technique.ResultsMean ± SD of NFL in RRMS was 82.25 ± 170.9, in PPMS was 22.08 ± 7.26, in SPMS was 95.82 ± 187.5, and in control group was 56.65 ± 125.4, there was high statistical substantial variations among the different groups while there was non-statistical variation between RRMS and PPMS groups, also there was no variation between PPMS and SPMS with regard to serum level of NFL. There is no significant correlation between the NFL and different cognitive tests.ConclusionSince sNfL did not strongly connect with cognitive function in MS patients, it is possible that it cannot be used as a substitute indicator for neuropsychological state in these groups.

Vancomycin population pharmacokinetics and dosing proposal for the initial treatment in obese adult patients.

The aim of this study was to develop a vancomycin population pharmacokinetic model in adult obese patients and propose covariate-based dosing individualization in order to maximize the achievement of the newly recommended PK/PD target, according to a revised consensus guideline from 2020. Therapeutic drug monitoring data from initial vancomycin therapy (first 3days of treatment) in adult obese (BMI ≥ 30kg/m2) patients from 2013 to 2022 were analyzed using a non-linear mixed-effects modeling method, and Monte Carlo simulations were then used to find the optimal dosage maximizing the PK/PD target attainment. A total of 147 vancomycin serum levels obtained from 138 patients were included in the analysis. Based on the covariate model diagnosis among all tested variables, no reliable predictor of vancomycin volume of distribution (Vd) was identified, while clearance (CL) was positively correlated with eGFR and lean body mass. Creatinine-based eGFR predicted vancomycin CL better than cystatin C-based eGFR. The median (interquartile range) value from conditional modes of individual estimates of Vd, CL, and elimination half-life in our population was 74.0 (70.5-75.4) L, 6.65 (4.95-8.42) L/h, and 7.7 (6.0-10.0) h, respectively. We proposed dosing individualization based on the covariate found in order to maximize the achievement of the newly recommended PK/PD target of the AUC/MIC ratio of 400-600. Clinical pharmacy/pharmacology interventions may lead to an improvement in vancomycin dosing with a reflection in PK/PD target attainment.

Expression and characterization of a thermostable monoacylglycerol lipase from thermophilic Geobacillus kaustophilus

Thermophilic Geobacillus kaustophilus HTA426 genome possesses a monoacylglycerol lipase (MAGL) gene. MAGLs can synthesize emulsifiers for use in the food and pharmaceutical industries from fatty acids and glycerol. They can also be used to analyze monoacylglycerol (MAG) levels in serum and food. The MAGL gene from strain HTA426 was artificially synthesized and heterologously expressed in Escherichia coli BL21(DE3). The recombinant His-tag fused MAGL (GkMAGL) was purified using a Ni2+-affinity column. The purified enzyme showed a temperature optimum at 65 °C and was stable up to 75 °C after 30 min incubation. In addition, the enzyme exhibited a pH optimum of 7.5 and was stable from pH 5.0 to 11.0. The enzyme hydrolyzed monoacylglycerols and showed the highest activity toward 1-monolauroylglycerol. The enzyme was stable in the presence of various organic solvents and detergents. The addition of Triton X-100 significantly increased GkMAGL activity. The thermal stability of the enzyme was higher than that of thermostable MAGL from Geobacillus sp. 12AMOR1 (12AMOR1_MAGL). Circular dichroism spectral analysis showed that the conformational stability of the GkMAGL was higher than that of 12AMOR1_MAGL at higher temperatures. These results indicate that the GkMAGL has useful features that can be used for various biotechnological applications.

Intoxications involving methoxyacetylfentanyl and U-47700: a study of 3 polydrug fatalities.

Novel synthetic opioids (NSOs) represent an emerging group of novel psychoactive substances, acting as agonists at the opioid receptors. NSOs include fentanyl-related compounds, e.g. methoxyacetylfentanyl (MeACF), and non-fentanyl analogs, e.g. "U compounds" including U-47700. Here we present three cases of death involving MeACF and U-47700, with particular reference to preliminary data on pharmacokinetics and tissue distribution.After a complete post-mortem examination, general unknown screenings and analysis of drugs of abuse were performed on postmortem samples by immunoassays, gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. To quantify the analytes of interest in post-mortem blood and tissues, the standard addition method was used. A toxicological significance score (TSS), weighing the role of the NSO in each death case, was assigned.Case 1 died at the hospital after consumption of U-47700, methadone (serum levels: 2,600ng/ml and 37ng/ml), tilidine and benzodiazepines. In case 2, U-47700 (204ng/ml) together with methadone (290ng/ml), flubromazepam (480ng/ml) and diazepam (300ng/ml) were detected in peripheral blood. In case 3, methoxyacetylfentanyl (266ng/ml), furanylfentanyl (4.3ng/ml) 4-ANPP (15ng/ml) and alprazolam (69ng/ml) were quantified in femoral blood. In all cases, the NSO likely contributed to the death (TSS = 3).NSOs appear to be often consumed in the setting of polydrug intoxications, especially in combination with other opioids and benzodiazepines, which often exert synergistic effects. The standard addition method remains the most reliable in post-mortem analysis and toxicological results should always be evaluated together with circumstantial and autopsy data.

Interleukin-8/CXCR1 Signaling Contributes to the Progression of Pulmonary Adenocarcinoma Resulting in Malignant Pleural Effusion.

Pulmonary adenocarcinoma (PADC) treatment limited efficacy in preventing tumor progression, often resulting in malignant pleural effusion (MPE). MPE is filled with various mediators, especially interleukin-8 (IL-8). However, the role of IL-8 and its signaling mechanism within the fluid microenvironment (FME) implicated in tumor progression warrants further investigation. Primary cultured cells from samples of patients with MPE from PADC, along with a commonly utilized lung cancer cell line, were employed to examine the role of IL-8 and its receptor, CXCR1, through comparative analysis. Our study primarily assessed migration and invasion capabilities, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties. Additionally, IL-8 levels in MPE fluid versus serum, along with immunohistochemical expression of IL-8/CXCR1 signaling in tumor tissue and cell blocks were analyzed. IL-8/CXCR1 overexpression enhanced EMT and CSC properties. Furthermore, the immunocytochemical examination of 17 cell blocks from patients with PADC and MPE corroborated the significant correlation between upregulated IL-8 and CXCR1 expression and the co-expression of IL-8 and CXCR1 in MPE with distant metastasis. In summary, the IL-8/ CXCR1 axis in FME is pivotal to tumor promotion via paracrine and autocrine signaling. Our study provides a therapeutic avenue for improving the prognosis of PADC patients with MPE.

Anti-Müllerian hormone (ovarian reserve) in rheumatoid arthritis patients: correlation with disease activity

BackgroundRheumatoid arthritis is considered one of the most common chronic inflammatory autoimmune diseases that lead to affection of several joints, as well as extra-articular organ involvement.Rheumatoid arthritis women tend to menopause somewhat earlier. This was attributed to primary ovarian insufficiency because of autoimmune disorders. Anti-Müllerian hormone is a marker used for evaluating preantral follicle reserve. It provides a very sensitive way to reflect the ovarian reserve and has become a crucial factor in determining it.The study aimed to show the influence of rheumatoid arthritis and its activity on ovarian reserve assessed using anti-Müllerian hormone serum levels.ResultsOur cross-sectional study involved 30 rheumatoid arthritis female patients with an age range between 25 and 35 years. The Disease Activity Score (DAS 28-ESR) was used to assess the degree of disease activity. Serum level of anti-Müllerian hormone was determined using quantitative enzyme-linked immunosorbent assay and the correlation with the disease activity as well as with the medications the patients were receiving was analyzed. A statistically significant relation was found amid the disease activity and the anti-Müllerian hormone level. Serum levels of anti-Müllerian hormone were found less in cases with high disease activity than in low to moderate cases. Different medications had no effect on anti-Müllerian hormone levels.ConclusionsRheumatoid arthritis high disease activity was linked to a diminished level of serum anti-Müllerian hormone.

Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis.

Although metabolic dysfunction-associated steatotic liver disease (MASLD) patients with a Fib-4 index >1.3 are recommended for fibrosis evaluation via elastography or biopsy, a more convenient method identifying high-risk populations requiring follow-up is needed. We explored the utility of serum levels of growth differentiation factor-15 (GDF15), a cell stress-responsive cytokine related to metabolic syndrome, for stratifying the risk of clinical events in MASLD patients. Serum GDF15 levels were measured in 518 biopsy-performed MASLD patients, 216 MASLD patients for validation, and 361 health checkup recipients with MASLD. In the biopsy-MASLD cohort, multivariate analysis indicated that the serum GDF15 level was a risk factor for liver cancer, independent of the fibrosis stage or Fib-4 index. Using a GDF15 cutoff of 1.75 ng/mL based on the Youden index, high-GDF15 patients, regardless of fibrosis status, had a higher liver cancer incidence rate. While patients with a Fib-4 index <1.3 or low-GDF15 rarely developed liver cancer, high-GDF15 patients with a Fib-4 index >1.3 developed liver cancer and decompensated liver events at significantly higher rates and had poorer prognoses. In the validation cohort, high-GDF15 patients had significantly higher incidences of liver cancer and decompensated liver events and poorer prognoses than low-GDF15 patients, whether limited to high-Fib-4 patients. Among health checkup recipients with MASLD, 23.0% had a Fib-4 index >1.3, 2.7% had a Fib-4 index >1.3 and >1.75 ng/mL GDF15. Serum GDF15 is a biomarker for liver cancer with high predictive capability and is useful for identifying MASLD patients requiring regular surveillance.

Pharmacologic blockade of nicotinic receptors in the suprachiasmatic nucleus increases ovarian atresia and inhibits follicular growth.

Reproduction in all mammalian species depends on the growth and maturation of ovarian follicles, that is, folliculogenesis. Follicular development can culminate with the rupture of mature follicles and the consequent expulsion of their oocytes (ovulation) or in atresia, characterized by the arrest of development and eventual degeneration. These processes are regulated by different neuroendocrine signals arising at different hypothalamic nuclei, including the suprachiasmatic nucleus (SCN). In the later, the activation of muscarinic receptors (mAChRs) and nicotinic receptors (nAChRs) by acetylcholine is essential for the regulation of the pre-ovulatory signals that stimulate the rupture of mature follicles. To evaluate the participation of the nAChRs in the SCN throughout the oestrous cycle in the regulation of the hypothalamic-pituitary-ovarian axis. For this purpose, 90-day-old adult female rats in metoestrus, dioestrus, proestrus or oestrus were microinjected into the left- or right-SCN with 0.3 μL of saline solution as vehicle or with 0.225 μg of mecamylamine (Mec), a non-selective antagonist of the nicotinic receptors, diluted in 0.3 μL of vehicle. The animals were sacrificed when they presented vaginal cornification, indicative of oestrus stage, and the effects of the unilateral pharmacological blockade of the nAChRs in the SCN on follicular development, ovulation and secretion of oestradiol and follicle-stimulating hormone (FSH) were evaluated. The microinjection of Mec decreased the serum levels of FSH, which resulted in a lower number of growing and healthy follicles and an increase in atresia. The higher percentage of atresia in pre-ovulatory follicles was related to a decrease in the number of ova shed and abnormalities in oestradiol secretion. We also detected asymmetric responses between the left and right treatments that depended on the stage of the oestrous cycle. The present results allow us to suggest that during all the stages of the oestrous cycle, cholinergic signals that act on the nAChRs in the SCN are pivotal to modulate the secretion of gonadotropins and hence the physiology of the ovaries. Further research is needed to determine if such signals are generated by the cholinergic neurons in the SCN or by cholinergic afferents to the SCN.

A randomized double blind placebo controlled trial to assess the safety and efficacy of a patented fenugreek (Trigonella foenum-graecum) seed extract in Type 2 diabetics.

Fenugreek plant (Trigonella foenum-graecum) constitutes a traditionally acclaimed herbal remedy for many human ailments including diabetes, obesity, neurodegenerative diseases, and reproductive disorders. It is also used as an effective anti-oxidative, anti-inflammatory, antibacterial, and anti-fungal agent. The seed of the plant is especially enriched in several bioactive molecules including polyphenols, saponins, alkaloids, and flavonoids and has demonstrated potential to act as an antidiabetic phytotherapeutic. A novel patented formulation (Fenfuro®) was developed in our laboratory from the fenugreek seeds which contained >45% furostanolic saponins (HPLC). A placebo-controlled clinical compliance study was designed to assess the effects of complementing Fenfuro® on a randomized group of human volunteers on antidiabetic therapy (Metformin and sulphonylurea) in controlling the glycemic index along with simultaneous safety assessment. In a randomized double-blind, placebo-controlled trial, 42 individuals (21 male and 21 female volunteers) in the treatment group (out of 57 enrolled) and 39 individuals (17 male and 22 female volunteers) in the placebo group (out of 47 enrolled), all on antidiabetic therapy with Metformin/Metformin with sulphonyl urea within the age group of 18-65 years were administered either 1,000 mg (500 mg × 2) (Fenfuro®) capsules or placebo over a period of 12 consecutive weeks. Fasting and postprandial glucose along with glycated hemoglobin were determined as primary outcomes to assess the antidiabetic potential of the formulation. Moreover, in order to evaluate the safety of the formulation, C-peptide and Thyroid Stimulating Hormone (TSH) levels as well as immunohematological parameters were assessed between the treatment and placebo groups at the completion of the study. After 12 weeks of administration, both fasting as well as postprandial serum glucose levels decreased by 38 and 44% respectively in the treatment group. Simultaneously, a significant reduction in glycated hemoglobin by about 34.7% was also noted. The formulation did not have any adverse effect on the study subjects as there was no significant change in C- peptide level and TSH level; liver, kidney, and cardiovascular function was also found to be normal as assessed by serum levels of key immunohematological parameters. No adverse events were reported. This clinical compliance study re-instated and established the safety and efficacy of Fenfuro® as an effective phytotherapeutic to treat hyperglycemia.

Association of maternal serum vitamin D level with fetal pulmonary artery Doppler indices and neonatal respiratory distress syndrome.

Respiratory distress syndrome (RDS) is potentially fatal in infants. The present study investigated the association of maternal serum vitamin D level with fetal pulmonary artery Doppler indices and neonatal RDS. This cross-sectional-analytical study was conducted on 260 mothers admitted for delivery. The maternal serum 25-hydroxyvitamin D level was measured and fetal main pulmonary artery Doppler indices were evaluated. The neonate's weight, apgar score, RDS, Umbilical cord arterial pH and neonatal intensive care unit admission were recorded. There was a significant relationship between RDS and the low level of vitamin D in the mother's serum. Mothers with low vitamin D had higher fetal pulmonary artery pulsatility index (PI) and peak systolic velocity (PSV) and lower acceleration time (AT) to ejection time (ET) ratio. Also, in neonates with RDS, pulmonary artery PI was higher, and PSV and the ratio of AT to ET were significantly lower than neonates without RDS. Neonates with lower one and 5-min apgar scores were born from mothers with lower vitamin D levels. Serum levels of vitamin D in pregnant mothers as well as fetal pulmonary artery Doppler indices are correlated to RDS. There is a significant relationship between the serum level of vitamin D in pregnant mothers and fetal pulmonary artery Doppler indices.

Serum Macrophage Colony Stimulating Factor Relates to the Severity and the Pregnancy Outcomes in Hypertensive Disorders Complicating Pregnancy.

This study aimed to assess the predictive value of macrophage colony stimulating factor (M-CSF) in the first trimester for hypertensive disorders complicating pregnancy (HDCP) and its association with disease severity and adverse pregnancy outcomes. HDCP pose significant risks to both maternal and fetal health. M-CSF is implicated in the pathogenesis of HDCP by promoting inflammation and endothelial damage. Serum levels of M-CSF were measured using enzyme-linked immunosorbent assay, and clinical characteristics and pregnancy outcomes were compared between groups. Pregnant women with HDCP had significantly higher levels of proteinuria, systolic blood pressure, and diastolic blood pressure compared to those with normal pregnancy. Among patients with HDCP, the severity of disease correlated positively with serum levels of M-CSF. Furthermore, M-CSF levels in the first trimester were significantly associated with adverse pregnancy outcomes. The findings suggest that M-CSF may serve as a potential biomarker for predicting HDCP and its severity, as well as adverse pregnancy outcomes. Early detection and monitoring of M-CSF levels could aid in identifying high-risk pregnancies and implementing appropriate interventions to improve maternal and fetal outcomes.

The Role of Serum Dickkopf1 and CKAP4 Levels in Diagnosing Colorectal Cancer and Measuring the Disease Severity: A Prospective Study.

Background and Objective: Colorectal cancer (CRC) is among the most common types of cancer. Although the disease is treatable in its early stages, five-year survival falls below 20% in the later stages. CEA and CA19-9 are tumor markers used in the diagnosis and follow-up of the disease in clinical practice; however, their diagnostic effectiveness is insufficient. Therefore, the identification of biomarkers that can be easily studied from serum and can diagnose CRC and determine its severity is highly important. In this context, dickkopf1 (DKK1) and cytoskeleton-associated protein 4 (CKAP4) are both promising biomarkers. Materials and Methods: Serum DKK1 and CKAP4 levels were measured in 55 patients with CRC and 40 healthy controls. The patients with CRC were divided into groups based on pathological stages and histological differentiation. The serum levels of both proteins in patients with CRC were measured preoperatively and 10 and 30 days postoperatively. Results: Serum DKK1 and CKAP4 were significantly higher in the CRC group than in the healthy controls (p < 0.05). Serum levels of both proteins rose in line with the disease stage and grade but decreased following surgical resection. A positive correlation was observed between tumor diameter and protein blood levels. The diagnostic efficacy of DKK1 and CKAP4 in CRC (approximately 95%) was higher than that of markers such as CEA and CA19-9. Conclusions: The DKK1 and CKAP4 serum values of patients with CRC are promising biomarkers. They can potentially be used in CRC management, namely, in the diagnosis and treatment of tumor response access and in tumor aggressiveness prediction.

Saiga antelope horn suppresses febrile seizures in rats by regulating neurotransmitters and the arachidonic acid pathway

BackgroundSaiga antelope horn (SAH) is a traditional Chinese medicine for treating febrile seizure (FS) with precise efficacy, but its mechanism of action and functional substances are still unclear. Given the need for further research on SAH, our group conducted studies to elucidate its mechanisms and active substances.MethodsAn FS rat pup model was constructed through intraperitoneal injection of LPS and hyperthermia induction. Behavioural indicators of seizures, hippocampal histopathological alterations, serum levels of inflammatory cytokines and hippocampal levels of neurotransmitters were observed and measured to investigate the effects of SAH on FS model rats. Hippocampal metabolomics and network pharmacology analyses were conducted to reveal the differential metabolites, key peptides and pathways involved in the suppression of FS by SAH.ResultsSAH suppressed FS, decreased the inflammatory response and regulated the Glu-GABA balance. Metabolomic analysis revealed 13 biomarkers of FS, of which SAH improved the levels of 8 differential metabolites. Combined with network pharmacology, a “biomarker-core target-key peptide” network was constructed. The peptides of SAH, such as YGQL and LTGGF, could exert therapeutic effects via the arachidonic acid pathway. Molecular docking and ELISA results indicated that functional peptides of SAH could bind to PTGS2 target, inhibiting the generation of AA and its metabolites in hippocampal samples.ConclusionIn summary, the functional peptides contained in SAH are the main material basis for the treatment of FS, potentially acting through neurotransmitter regulation and the arachidonic acid pathway.Graphical abstract