Hyperhomocysteinemia and Associated Biological Markers in a Congolese Population of Type 2 Diabetes Mellitus in Brazzaville

The search for new biomarkers predictive of type 2 diabetes currently constitutes a research avenue in Bioclinical. Total homocysteine remains a preferred target due to its involvement in the occurrence of degenerative complications in type 2 diabetics. The aim of this work was to study hyperhomocysteinemia and other biochemical markers associated with T2D in the Congolese population. This was an analytical case-control study carried out between October 2022 and October 2023. The study population consisted of 150 subjects including 100 T2D patients and 50 control subjects. The main clinical data were collected on a pre-established form. Homocysteine determination was carried out by the sandwich ELISA method. The other biochemical markers were measured by colorimetric enzymatic methods. Hyperhomocysteinemia was present in 27.3% (41/150) of the entire study population. Type 2 diabetics had a frequency of hyperhomocysteinemia of 36% (36/100) and control 10% (5/50) (p = 0.001). The mean hyperhomocysteinemia concentration was 31.9 μmol/l with extremes ranging from 18 to 103 μmol/l. Means of biological markers between diabetics and controls showed a statistically significant difference (p = 0.01). The risk factors associated with this HHcy were: sex (OR = 3.5), age (OR = 9.4), sedentary lifestyle (OR = 3.4) and glycosylated hemoglobin (OR = 12) with a p-value <0.05 respectively. Our results suggest that hyperhomocysteinemia can be considered as a predictive biomarker in the bioclinic of Congolese type 2 diabetic patients.

An Overview on Biological Markers in Reproductive and Developmental Toxicology: Concepts, Definitions and Use in Risk Assessment

Reproduction and development are complex couple-dependent processes. Risk assessment for these health outcomes requires the use of biomarkers to link exposures to disease. Biological markers of susceptability, external dose, internal dose, biologically effective dose, early or late biological responses, altered reproductive or developmental function, and reproductive or developmental disease are introduced. Using these biomarkers it is possible to define a biologically based risk assessment methodology for reproductive and developmental toxicity. Risk assessment for reproductive toxicity requires definition of male and female fecundity, couple-specific factors, spontaneous abortion, rate, and other factors. Using using sperm count as a biomarker for male fecundity, an example of a reproductive risk assessment using biomarkers is performed.

Biological Markers on Human Pregnancy

This article reviews a selected set of recently described pregnancy-associated proteins which possess potential for both signaling pregnancy onset and monitoring its course. These molecules are compared and contrasted with human chorionic gonadotropin, the first pregnancy-associated protein to be discovered, and the standard biomarker of pregnancy to which all others must still be referenced. Recent advances in hCG research have focused on the structural determination and diagnostic significance of the subunits and fragments of the hCG molecule, particularly in urine. An outline of the potential utility of this approach is also presented.

Review of the potential value of serum interleukin levels as prognostic biomarkers of liver failure

Liver failure(LF)is prevalent in China and is characterized by complex path-ogenesis,challenging clinical management,poor prognosis,and rising incidence and mortality rates.The immune status is an important factor affecting LF prognosis.Interleukins(Ils)are a type of cytokine that act and interact with multiple cells,including immune cells.These signaling molecules play important roles in intercellular information transmission,including the regulation of immune cells;mediation of the activation,proliferation,and differentiation of T and B cells;and orchestration of the inflammatory response.To date,many studies have explored the correlation between IL expression and liver disease prognosis,but few studies have evaluated Ils as the prognostic biomarkers of LF.This article reviews the potential use of Ils as the prognostic biomarkers of LF.Particularly,it evaluates the predictive values of IL-21,IL-22,and IL-31,the three often overlooked yet promising prognostic biomarkers,in predicting suscept-ibility to LF.Harnessing biomarkers for early prognostic insights can facilitate tailored treatment strategies and enhance patient survival.Thus,this article focuses on the identification of IL-21,IL-22,and IL-33 as biomarkers in preclinical and clinical studies on LF and reviews their role as biomarkers in the pathogenesis and diagnosis of LF.

Study of biological markers in skin quality treatment by subcutaneous injection of a stabilized composition of 26 mg/mL of high molecular weight HA

Aim:Hyaluronic acid(HA)injectables have gained rapid acceptance for the treatment of skin rejuvenation.A novel HA/sorbitol composition intended for skin quality improvement containing 2.6%of high molecular weight HA stabilized by sorbitol was recently designed to be injected subcutaneously.The aim of this study was to assess the expression of biological markers of skin quality after administration of the composition.Methods:The HA/sorbitol composition was evaluated after injection into the superficial adipose tissue with ex vivo cultured human skin explants versus a product comparator to study the general morphology of the skin tissues and the expression of HA,elastin,collagen type Ⅰ,collagen type Ⅲ,and fibrillin-1 in the dermal layer.Results:The results demonstrate that the HA/sorbitol composition is able to boost the production of HA,elastin,collagen type Ⅰ,collagen type Ⅲ,and fibrillin-1 in the dermis while providing a proper quality of skin morphology.Conclusion:The HA/sorbitol composition improved biological markers of skin quality in the dermis after product injection into the superficial adipose tissue.This novel composition can be considered as an attractive solution to treat skin aging by injecting a specific HA/sorbitol formulation to strategically target the subcutaneous tissue to improve the quality of the different layers of the skin.

Metabolomic Analysis in Saliva and Different Brain Regions of Older Mice with Postoperative Delirium Behaviors

Objective Postoperative delirium(POD)has become a critical challenge with severe consequences and increased incidences as the global population ages.However,the underlying mechanism is yet unknown.Our study aimed to explore the changes in metabolites in three specific brain regions and saliva of older mice with postoperative delirium behavior and to identify potential non-invasive biomarkers.Methods Eighteen-month-old male C57/BL6 mice were randomly assigned to the anesthesia/surgery or control group.Behavioral tests were conducted 24 h before surgery and 6,9,and 24 h after surgery.Complement C3(C3)and S100 calcium-binding protein B protein(S100beta)levels were measured in the hippocampus,and a metabolomics analysis was performed on saliva,hippocampus,cortex,and amygdala samples.Results In total,43,33,38,and 14 differential metabolites were detected in the saliva,hippocampus,cortex,and amygdala,respectively.“Pyruvate”“alpha-linolenic acid”and“2-oleoyl-1-palmitoy-snglycero-3-phosphocholine”are enriched in one common pathway and may be potential non-invasive biomarkers for POD.Common changes were observed in the three brain regions,with the upregulation of 1-methylhistidine and downregulation of D-glutamine.Conclusion Dysfunctions in energy metabolism,oxidative stress,and neurotransmitter dysregulation are implicated in the development of POD.The identification of changes in the level of salivary metabolite biomarkers could aid in the development of noninvasive diagnostic methods for POD.

Neutral Red Retention by Earthworm Coelomocytes: A Biomarker of Cadmium Contamination in Soil

The earthworm Metaphire posthuma were used as a model to assess the toxic potential of cadmium incorporated into the soil by environmental or human activities. The retention period of neutral red in the lysosomes of the coelomocytes was used as a biomarker. The viability of harvested coelomocytes by a non_invasive extrusion protocol was 93% with no alteration by the dye during experimentation. The control cells retained dye for 119 and 121 min in normal soil and KCl, respectively, whereas a linear decline in the retention time in the treated earthworm coelomocytes was observed. This illustrated that the presence of cadmium caused damage to the lysosomes of the coelomocytes.

Cell-free plasma hypermethylated CASZ1, CDH13 and ING2 are promising biomarkers of esophageal cancer

Identifying sensitive and specific biomarkers for early detection of cancer is immensely imperative for early diagnosis and treatment and better clinical outcome of cancer patients. This study aimed to construct a specific DNA methylation pattern of cancer suppressor genes and explore the feasibility of applying cell-free DNA based methylation as a biomarker for early diagnosis of esophageal squamous cell carcinoma(ESCC). We recruited early stage ESCC patients from Yangzhong County, China. The Illumina Infinium 450 K Methylation BeadChip was used to construct a genome-wide DNA methylation profile. Then, differentiated genes were selected for the validation study using the Sequenom MassARRAY platform. The frequency of methylation was compared between cancer tissues, matched cell-free DNAs and normal controls. The specific methylation profiles were constructed, and the sensitivity and specificity were calculated. Seven CG sites in three genes CASZ1, CDH13 and ING2 were significantly hypermethylated in ESCC as compared with normal controls. A significant correlation was found between the methylation of DNA extracted from cancer tissues and matched plasma cell-free DNA, either for individual CG site or for cumulative methylation analysis. The sensitivity and specificity reached 100% at an appropriate cut-point using these specific methylation biomarkers. This study revealed that aberrant DNA methylation is a promising biomarker for molecular diagnosis of esophageal cancer. Hypermethylation of CASZ1,CDH13 and ING2 detected in plasma cell-free DNA can be applied as a potential noninvasive biomarker for diagnosis of esophageal cancer.

CT Texture Analysis: A Potential Biomarker for Evaluating KRAS Mutational Status in Colorectal Cancer

Objective Texture analysis is deemed to reflect intratumor heterogeneity invisible to the naked eyes.The aim of this study was to evaluate the feasibility of assessing the KRAS mutational status in colorectal cancer(CRC)patients using CT texture analysis.Methods This retrospective study included 92 patients who had histopathologically confirmed CRC and underwent preoperative contrast-enhanced CT examinations.The patients were assigned into a training cohort(n=51)and a validation cohort(n=41).We placed the region of interest in the tumour regions on the selected axial images using software of lexRad to extract a series of quantitative parameters based on the spatial scaling factors(SSFs),including mean,standard deviation(SD),entropy,mean of positive pixels(MPP),skewness,and kurtosis.The texture parameters and clinical characteristics(age,gender,tumour location,histopathology;tumour size,1 N,M stages)were compared between the mutated and wild-type KRAS patient groups in training cohort and validation cohort.Before building the multiple feature classifier,we calculated the correlations of the features using Pearsons correlation coefficient,and if any two features were significantly correlated,the one with lower AUC was removed.Ultimately,only the most discriminative isolated features were combined to train a supporting vector machine(SVM)classifier.The receiver operating characteristic(ROC)curve was processed for evaluating the diagnostic efficiency of texture parameters in differentiating CRC patients with mutated KRAS from those with wild-type KRAS.Results None of the clinical characteristics were significant different between CRC patients with wild-type KRAS and mutated KRAS in both cohorts.For predicting the expression of mutated KRAS in CRC patients,the perfect model which combined skewness on SSF 5 by unenhanced CT,entropy on SSF 2,skewness and kurtosis on SSF 0,and kurtosis and mean on SSF 3 by enhanced CT,showed a desirable AUC of 0.951(95%CI:0.895-1,P<0.001),with a sensitivity of 88.9%and a specificity of 91.7%,when the cut-off value was 0.46 in the training cohort;while in the validation cohort,the AUC value was 0.995(95%CI:0.982-1,P<0.001),the sensitivity was 100%,and the specificity was 93.7%when the cut-off value was 0.28.Conclusion It is feasible to evaluate the KRAS mutational status in CRC using CT texture analysis.

Monocyte chemoattractant protein-1, transforming growth factor-β1, nerve growth factor, resistin and hyaluronic acid as serum markers：comparison between recurrent acute and chronic pancreatitis

BACKGROUND： Diagnostic parameters that can predict the presence of chronic pancreatitis（CP） in patients with recurrent pain due to pancreatitis would help to direct appropriate therapy. This study aimed to compare the serum levels of monocyte chemoattractant protein-1（MCP-1）, transforming growth factor-β1（TGF-β1）, nerve growth factor（NGF）, resistin and hyaluronic acid（HA） in patients with recurrent acute pancreatitis（RAP） and CP to assess their ability to differentiate the two conditions.METHODS： Levels of serum markers assessed by enzymelinked immunosorbent assay（ELISA） were prospectively compared in consecutive patients with RAP, CP and in controls and stepwise discriminant analysis was performed to identify the markers differentiating RAP from CP.RESULTS： One hundred and thirteen consecutive patients（RAP=32, CP=81） and 78 healthy controls were prospectively enrolled. The mean（SD） age of the patients was 32.0（14.0）years; 89（78.8%） were male. All markers were significantly higher in CP patients than in the controls（P〈0.001）; MCP-1NGF and HA were significantly higher in RAP patients than in the controls（P〈0.001）. Stepwise discriminant analysis showed significant difference（P=0.002） between RAP and CP for resistin with an accuracy of 61.9%, discriminant scores of ≤-0.479 and ≥0.189 indicating RAP and CP, respectively. The other markers had no differential value between RAP and CP.CONCLUSION： Serum resistin is a promising marker to differentiate between RAP and CP and needs validation in future studies, especially in those with early CP.

Evolution of Biochemical, Hematological, Inflammatory and Immunological Markers among Person Living with HIV-1 on ART in Burkina Faso

In Human immunodeficiency virus infected (HIV+) patients, deregulation of regulatory T (Treg) cells can be deleterious for the development of an efficient anti-HIV specific immune response with an inappropriate immune activation despite anti-retroviral therapy (ART). In addition, infection and ART have the potential to cause hematological and biochemical abnormalities that can lead to the discontinuation of ART. The aim of this study was to assess hematological, biochemical and immunological abnormalities in HIV+ patients’ naïve to ART and 6 months after ART initiation. In a cross-sectional study, 11 HIV+ patients and 09 healthy individuals (control group) were voluntarily recruited. At inclusion, blood samples were taken before administration of ART. All hematological, biochemical, immunological parameters and viral load were measured and assessed at inclusion (M0) and three and/or six months later (M3, M6). Higher level of white blood cells and CD4+ T lymphocytes (p = 0.032, 0.038 respectively) were observed in HIV+ patients. ART also had significantly effect on the level of red blood cells (p = 0.04) and Hb (p = 0.015). The inflammatory markers, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) that were significantly increased by HIV infection, tended to decrease for ESR and revert to levels similar to those of control for CRP. Analysis of CD4+CD25+ cells and CD4+Foxp3+CD25+ showed significantly elevated levels of activated form of all CD4+ cells and Treg cells. Interestingly, six months after initiation of ART, the average percentage of CD4+CD25+ was not significantly different from control group (p = 0.382). Our study provides information about the evolution of the activated form of all CD4 cells and Treg cells and points out the necessity to monitor hematological and biochemical parameters in order to detect and prevent toxicity, improve the quality of life and reduce the risk of mortality.

Endotoxins in the prostatic secretions of chronic prostatitis patients:a need for further biomarkers through the use of proteomics

Dear Sir,Dai et al.[1] must be commended on their useful investigation of the clinical significance of endotoxins in the expressed prostatic secretions （EPS） of chronic prostatitis （CP） patients. However, we take issue with their conclusion. The conclusion that EPS endotoxin determination is helpful in diagnostic confirmation is plausible,

The diagnostic value of multiple tumor markers in malignantovarian neoplasms

Objective:To study the diagnostic value of multiple tumor markers in malignant ovarian neoplasm.Methods:Sera obtained from 430 patients with ovarian masses (110 cases were malignant ovarian tumors,320 cases were benign ovarian tumors) before operation,and from 50 healthy women as control.Serologic examination of tumor markers included CA125,TSGF,SA,CEA,AFP,HCG and Fer.Results:The serum levels of CA125,TSGF,SA and Fer in patients with ovarian cancer were higher than those in patients with benign ovarian tumors (P<0.05),also in control group (P<0.05).In the diagnostic value of application for malignant ovarian neoplasm,CA125,TSGF and SA were better than the others.The sensitivity,specificity and accuracy in diagnosis of ovarian cancer were 86.4%,82.8%and 83.7% respectively for CA125 alone,78.2%,81.3%and 80.5% for TSGF alone,74.5%,81.9%and 80.0% for SA alone,whereas 95.5%,45.6%and 58.4% for multiple tumor markers combined in which 1 or more indices showed positive,93.6%,80.6%and 84.0% for that in which 2 or more indices showed positive,and 87.3%,90.3%and 89.5% for that in which 3 or more indices show positive.Conclusion:multiple tumor markers examination could improve the diagnosis of ovarian cancer,and examination of CA125,TSGF and SA combined is most ideal.

Commentary on: Mobley AJ, Lam YW, Lau KM, Pais VM, Lesperance JO, Steadman B, et al. Monitoring the serological Proteome Colon, the latest modality in prostate cancer detection. J Urol 2004; 172: 331-7.

This manuscript examines the utility, utilizing the Ciphergen Protein Biosystem II, to develop a fingerprint for the diagnosis of prostate cancer. The investigators compared samples from control individuals as well as those with prostate cancer. In doing so, they utilize several chip platforms on which to examine the resulting

Present and future possibilities for early diagnosis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) represents the fifth most common cancer in the world,and the third most frequent oncological cause of death.The incidence of HCC is on the increase.HCC typically develops in patients with chronic liver diseases,and cirrhosis,usually with viral etiology,is the strongest predisposing factor.Nowadays HCC diagnosis is a multistage process including clinical,laboratory,imaging and pathological examinations.The prognosis of HCC is mostly poor,because of detection at an advanced,non-resectable stage.Potentially curative treatment(surgery) is limited and really possible only for cases with small HCC malignancies.For this reason,more effective surveillance strategies should be used to screen for early occurrence of HCC targeted to the population at risk.So far,the generally accepted serological marker is α-fetoprotein(AFP).Its diagnostic accuracy is unsatisfactory and questionable because of low sensitivity,therefore there is a strong demand by clinicians for new HCC-specific biomarkers.In this review,we will focus on other biomarkers that seem to improve HCC diagnosis,such as AFP-L3,des-γ-carboxyprothrombin,α-l-fucosidase,,γ-glutamyl transferase,glypican-3,squamous cell carcinoma antigen,a new generation of immunoglobulin M-immunocomplexes,and very promising geneexpression profiling.

Increase of beta-amyloid and C-reactive protein in liver transplant recipients with postoperative cognitive dysfunction

BACKGROUND: Postoperative cognitive dysfunction (POCD) is an adverse condition characterized by declined cognitive functions following surgeries and anesthesia. POCD has been associated with increased hospital stay and mortality. There are histological similarities to Alzheimer’s disease. Most early studies were conducted in patients receiving cardiac surgery. Since there is no information about POCD in liver transplant recipients, we measured the incidence of POCD in patients after liver transplantation and examined the correlation between neurological dysfunction and biological markers of dementia- based diseases. METHODS: We studied 25 patients who had a liver transplan- tation between July 2008 and February 2009. Patients with prior encephalopathy or risk factors associated with the development of POCD were excluded from the study. Five validated neuropsychiatric tests were used for diagnosis. The diagnosis was based on one standard deviation decline in two of the five neuropsychiatric tests. The correlation between patient variables and the development of POCD was examined. Serum levels of beta-amyloid and C-reactive protein were measured by standard ELISA and compared between patients with and without POCD. RESULTS: POCD was present in 11 (44%) of the 25 patients. Patients with POCD had significantly higher MELD scores, were more often Child-Pugh class C and received more blood transfusion during surgery. The serum beta-amyloid protein and C-reactive protein concentrations were significantly increased at 24 hours after surgery in the POCD group.CONCLUSIONS: The incidence of POCD in our group of liver transplant patients was greater than that reported in other surgical patients. The increase in the serum biomarkers of dementia in the POCD patients supports the hypothesis that chronic cognitive defects are due to a process similar to that seen in Alzheimer’s disease.

骨转移前列腺癌病人升高的血清miR-141水平与增多的骨转移病变数相关

The skeleton is the most common metastatic organ in patients with prostate cancer （PCa）. Non-invasive biomarkers that can facilitate the detection and monitoring of bone metastases are highly desirable. We designed this study to assess the expression patterns of serum miR-141 in patients with bone-metastatic PCa. Serum samples were collected to measure the miR-141 level in 56 patients, including six with benign prostatic hyperplasia （BPH）, 20 with localized PCa and 30 with bone-metastatic PCa （10 with hormone-naive PCa, 10 with hormone-sensitive PCa and 10 with hormone-refractory PCa）. A bone scan was performed for each patient with PCa to assess the number of bone lesions. The quantification of serum miR-141 levels was assayed by specific TaqMan qRT-PCR. The results showed that serum miR-141 levels were elevated in patients with bone metastasis （P〈O.O01）. There was no statistically significant difference in the serum miR-141 levels between patients with BPH and patients with localized PCa. Using Kendall＇s bivariate correlation test, both the Gleason score and the number of bone-metastatic lesions were found to correlate with serum miR-141 levels （P=0.012 and P〈O.O01, respectively）. The serum miR-141 level was found to be positively correlated with alkaline phosphatase （ALP） level in patients with skeletal metastasis, using Pearson＇s bivariate correlation test. No relationship was found between the serum miR-141 level and the serum prostate-specific antigen （PSA） level. We concluded that serum miR-141 levels are elevated in patients with bone-metastatic PCa and that patients with higher levels of serum miR-141 developed more bone lesions. Furthermore, serum miR-141 levels are correlated with serum ALP levels but not serum PSA levels.

Circulating tumor cell isolation:the assets of filtration methods with polycarbonate track-etched filters

Circulating tumor cells （CTCs） arise from primary or secondary tumors and enter the bloodstream by active or passive intravasation. Given the low number of CTCs, enrichment is necessary for detection. Filtration methods are based on selection of CTCs by size using a filter with 6.5 to 8 pm pores. After coloration, collected CTCs are evaluated according to morphological criteria. Immunophenotyping and fluorescence in situ hybridization techniques may be used. Selected CTCs can also be cultivated in vitro to provide more material. Analysis of genomic mutations is difficult because it requires adapted techniques due to limited DNA materials. Filtration-selected CTCs have shown prognostic value in many studies but multicentric validating trials are mandatory to strengthen this assessment. Other clinical applications are promising such as follow-up, therapy response prediction and diagnosis. Microfluidic emerging systems could optimize filtration-selected CTCs by increasing selection accuracy.

Advancement in biochemical assays in andrology

Determination of markers of sperm function, accessory sex gland secretion and silent male genital tractinflammation is of considerable diagnostic value in the evaluation of male infertility. The introduction of biochemicaltests into the analysis of male factor has the advantage that standardized assays with a coefficient of variationcharacteristic of clinical chemistry are performed, in contrast to biological test systems with a large variability.Biochemical parameters may be used in clinical practice to evaluate the sperm fertilizing capacity (acrosin, aniline blue,ROS), to characterize male accessory sex gland secretions (fructose, α-glucosidase, PSA), and to identify men withsilent genital tract inflammation (elastase, C'3 complement component, coeruloplasmin, IgA, IgG, ROS).

Clinical significance of EGF and EGFR expression changes in cryptorchid boys

AIM: To explore the changes of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) expressions in cryptorchid children and their clinical significance. METHODS: The level of serum EGF was measured by radioimmunoassay (RIA) and the expression of EGFR by immunohistochemistry. RESULTS: (1) The level of serum EGF was significantly lower in cryptorchid children than in normal subjects at age group of 5-9 years (P