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Introduction: Surgical site infections (SSIs) remain the major cause of morbidity and mortality in the postoperative period and are important surgical and hospital quality indicators. In this context, our study aims to identify SSIs associated risk factors and to develop a predictive model. Methodology: 2521 patients who underwent surgery, between June 2018 and May 2019, in four surgery departments, at the Taza Provincial Hospital (Morocco) were diagnosed for SSI according to the standards of the Center for Disease Control and Prevention. The SSIs’ risk factors were assessed by univariate statistical analysis and logistic regression using the Scikit Learn function of Python. Results: The average age of the studied population was 35 ± 1 years. The overall SSI incidence was 6.3% (17.95%, 6.86%, 6.67% and 3.16% respectively in child, female, male and gynaecological-obstetrical surgeries. The univariate statistical analysis has shown a highly significant (p < 0.001) and a very significant (p < 0.01) relationship between SSIs and almost all risk factors; and the logistic regression model has revealed a strong association between SSI and people who have had previous surgery, urinary catheter, antibiotic use duration, co-morbidity, American Society of Anesthesiologists (ASA) score, duration of intervention, emergency preoperative and postoperative durations, service, specialty and age range. The prediction score exceeds 96% which justifies our model’s quality. Conclusions: SSIs are generally frequent among postoperative patients. Therefore, pre-operative preparation, post-operative surveillance and the environment quality of the wards are necessary to reduce SSI rates in the hospital.

Decision trees are among the most popular classifiers in machine learning, artificial intelligence, and pattern recognition because they are accurate and easy to interpret. During the tree construction, a node containing too few observations (weak node) could still get split, and then the resulted split is unreliable and statistically has no value. Many existing machine-learning methods can resolve this issue, such as pruning, which removes the tree’s non-meaningful parts. This paper deals with the weak nodes differently; we introduce a new algorithm Enhancing Weak Nodes in Decision Tree (EWNDT), which reinforces them by increasing their data from other similar tree nodes. We called the data augmentation a virtual merging because we temporarily recalculate the best splitting attribute and the best threshold in the weak node. We have used two approaches to defining the similarity between two nodes. The experimental results are verified using benchmark datasets from the UCI machine-learning repository. The results indicate that the EWNDT algorithm gives a good performance.

BACKGROUND Persistent inflammation in HIV infection is associated with elevated cardiovascular disease (CVD) risk, even with viral suppression. Identification of novel surrogate biomarkers can enhance CVD risk stratification and suggest novel therapies. We investigated the potential of interleukin 32 (IL-32), a proinflammatory multi-isoform cytokine, as a biomarker for subclinical carotid artery atherosclerosis in virologically suppressed women living with HIV (WLWH). METHODS AND RESULTS Nested within the Women's Interagency HIV Study, we conducted a cross-sectional comparison of IL-32 between 399 WLWH and 100 women without HIV, followed by a case-control study of 72 WLWH (36 carotid artery plaque cases vs. 36 age-matched controls without plaque). Plasma IL-32 protein was measured by ELISA, and mRNA of IL-32 isoforms (IL-32α, β, γ, D, e, and θ) was quantified by reverse transcription polymerase chain reaction from peripheral blood mononuclear cells. Plasma IL-32 protein levels were higher in WLWH compared with women without HIV (P = 0.02). Among WLWH, although plasma IL-32 levels did not differ significantly between plaque cases and controls, expression of IL-32 isoforms α, β, and e mRNA was significantly higher in peripheral blood mononuclear cells from cases (P = 0.01, P = 0.005, and P = 0.018, respectively). Upregulation of IL-32β and IL-32e among WLWH with carotid artery plaque persisted after adjustment for age, race/ethnicity, smoking, systolic blood pressure, body mass index, and history of hepatitis C virus (P = 0.04 and P = 0.045); the adjusted association for IL-32α was marginally significant (P = 0.07). CONCLUSIONS IL-32 isoforms should be studied further as potential CVD biomarkers. This is of particular interest in WLWH by virtue of altered IL-32 levels in this population.

Background The development of acute kidney injury (AKI) is an important indicator of clinical outcomes after cardiac surgery. Elevated preoperative hemoglobin A1c level may be associated with acute kidney injury in patients undergoing coronary artery bypass grafting. This study will investigate the association of preoperative HbA1c levels with AKI after isolated coronary artery bypass grafting (CABG). Results Forty patients undergoing elective CABG were enrolled in this cohort study. Patients are divided into 2 equal groups who underwent isolated coronary artery bypass grafting (CABG): patients with preoperative HbA1c 5.7–6.4% (group A) (prediabetics) and patients with preoperative HbA1c > or = 6.5% (group B) (diabetics). Acute kidney injury according to the Kidney Disease: Improving Global Outcomes criteria developed in 11 patients (27.5%). There was a significant difference between the two groups as regards postoperative urinary NGAL, creatinine level on the 1st day, creatinine level on the 2nd day, urine output on the 1st day, and urine output on the 2nd day (p value was 0.001, 0.002, 0.006, 0.0002, and 0.012 respectively). Postoperative ICU stay duration was statistically significant in the diabetic group (P value 0.009). The need for renal replacement therapy was higher in the diabetic group, but it was not statistically significant between the two groups. Roc analysis shows AUC 0.922 with a significant p value ( Conclusion This study revealed that elevated preoperative HbA1c level above 7% showed an increase in incidence of post CABG acute kidney injury along with increase length of postoperative ICU stay.

In chronic hepatitis C (CHC), Toxoplasma gondii infection can lead to more severe diseases and is capable of changing the disease course. Former studies were concerning anti-T. gondii IgG/IgM seroprevalence in CHC patients regardless the antigenic proteins that are associated with active infection. Therefore, this study aimed to evaluate association between prevalence of 36-KDa T. gondii antigen (TAg) and both CHC progression and liver and viral biochemical parameters. One hundred-twenty five CHC patients (65 with fibrosis and 60 with cirrhosis) and forty healthy controls constituted this study. Demographics and clinical data were collected. Both TAg and HCV-NS4 were identified using ELISA. In contrast to healthy controls (0%), both seropositivity (P = 0.043) and mean serum level (P = 0.025) of TAg were higher in cirrhotic patients (43.3 %; 1.2 ± 0.2 ng/mL) compared to fibrotic patients (26.2 %; 0.7 ± 0.1 ng/mL). T. gondii infection was significantly (P

Chronic hepatitis C (CHC) leads eventually to liver fibrosis, advanced hepatic disease and related deaths. Therefore, it is very important to assess clinical risk factors associated with rapid CHC and hepatic fibrosis progression. Former studies reported diabetes mellitus synergistic interactions with other host factors to fibrosis progression. Here, we aimed to evaluate the association between elevated blood glucose levels and CHC progression according to METAVIR system in patients chronically infected with HCV-genotype 4 and to evaluate the correlation between elevated glucose levels and liver- and viral-related biochemical parameters. A total of 160 patients with CHC (80 with liver fibrosis and 80 with cirrhosis) and 40 healthy volunteers, negative for HCV, were included. Our results revealed that cirrhotic patients had high (

Mammography, magnetic resonance imaging (MRI), and ultrasound are useful tools that can be used in breast cancer (BC) screening but these methods have various limitations. Thus, finding diagnostic biomarkers may be a useful alternative choice.A total of 142 females with breast diseases (40 females with benign conditions and 102 females with BC) were included in the study. In addition to age- and sex-matched 29 normal females as a negative control. The level of collagen III was detected using the ELISA technique. It was (21.29±3.14 µg/ml) in sera of females with BC higher than in benign (13.91±2.65 µg/ml) and in normal (5.69±0.43 µg/ml) females. Collagen III yielded an AUC of 0.86 to differentiate BC from normal females and an AUC of 0.62 to differentiate BC females from those with benign conditions. Moreover, AUC was risen to 0.72 to differentiate females with BC from those without BC. While the index provided values that were significantly (P

Background Human IL-32 is a polyfunctional cytokine that was initially reported to inhibit HIV-1 infection. However, recent data suggest that IL-32 may enhance HIV-1 replication by activating the HIV-1 primary targets, CD4 T-cells. Indeed, IL-32 is expressed in multiple isoforms, some of which are proinflammatory, whereas others are anti-inflammatory. Setting and methods Here, we aimed to determine the relative expression of IL-32 isoforms and to test their inflammatory nature and potential to induce HIV-1 production in latently infected cells from virologically suppressed HIV-infected individuals. IL-32 and other cytokines were quantified from plasma and supernatant of CD4 T-cells by ELISA. Transcripts of IL-32 isoforms were quantified by qRT-PCR in peripheral blood mononuclear cells. The impact of recombinant human IL-32 isoforms on HIV-1 transcription was assessed in CD4 T-cells from HIV-1cART individuals by qRT-PCR. Results All IL-32 isoforms were significantly upregulated in HIV-1cART compared to HIV individuals with IL-32β representing the dominantly expressed isoform, mainly in T-cells and NK-cells. At the functional level, although IL-32γ induced typical proinflammatory cytokines (IL-6 and IFN-γ) in TCR-activated CD4 T-cells, IL-32α showed an anti-inflammatory profile by inducing IL-10 but not IL-6 or IFN-γ. However, IL-32β showed a dual phenotype by inducing both pro- and anti-inflammatory cytokines. Interestingly, consistent with its highly pro-inflammatory nature, IL-32γ, but not IL-32α or IL-32β, induced HIV-1 production in latently infected CD4 T-cells isolated from combined antiretroviral therapy-treated individuals. Conclusions Our data report on the differential expression of IL-32 isoforms and highlight the potential role of IL-32, particularly the γ isoform, in fueling persistent inflammation and transcription of viral reservoir in HIV-1 infection.

Summary The crosstalk between intestinal epithelial cells (IECs) and Th17-polarized CD4+ T cells is critical for mucosal homeostasis, with HIV-1 causing significant alterations in people living with HIV (PLWH) despite antiretroviral therapy (ART). In a model of IEC and T cell co-cultures, we investigated the effects of IL-17A, the Th17 hallmark cytokine, on IEC ability to promote de novo HIV infection and viral reservoir reactivation. Our results demonstrate that IL-17A acts in synergy with TNF to boost IEC production of CCL20, a Th17-attractant chemokine, and promote HIV trans-infection of CD4+ T cells and viral outgrowth from reservoir cells of ART-treated PLWH. Importantly, the Illumina RNA-sequencing revealed an IL-17A-mediated pro-inflammatory and pro-viral molecular signature, including a decreased expression of type I interferon (IFN-I)-induced HIV restriction factors. These findings point to the deleterious features of IL-17A and raise awareness for caution when designing therapies aimed at restoring the paucity of mucosal Th17 cells in ART-treated PLWH., Graphical abstract, Highlights • IL-17A acts in synergy with TNF to enhance CCL20 production in IEC exposed to HIV • IL-17A/TNF-activated IEC efficiently promote HIV trans-infection of CD4+ T cells • IL-17A reprograms IEC to boost HIV outgrowth from CD4+ T cells of ART-treated PLWH • IL-17A decreases the expression of IFN-I-induced HIV restriction factors in IEC, Immunology; Immune response; Virology

Objectives Untreated HIV infection was previously associated with IL-32 overexpression in gut epithelial cells (IEC). Here, we explored IL-32 isoform expression in the colon of people living with HIV (PLWH) receiving antiretroviral therapy (ART) and IL-32 triggers/modulators in IEC. Design Sigmoid colon biopsies (SCB) and blood were collected from ART-treated PLWH (HIV + ART; n = 17; mean age: 56 years; CD4 counts: 679 cells/μl; time on ART: 72 months) and age-matched HIV-uninfected controls (HIVneg; n = 5). The IEC line HT-29 was used for mechanistic studies. Methods Cells from SCB and blood were isolated by enzymatic digestion and/or gradient centrifugation. HT-29 cells were exposed to TLR1-9 agonists, TNF-α, IL-17A, and HIV. IL-32α/β/γ/D/e/θ and IL-17A mRNA levels were quantified by real-time RT-PCR. IL-32 protein levels were quantified by ELISA. Results IL-32β/γ/e isoform transcripts were detectable in the blood and SCB, with IL-32β mRNA levels being predominantly expressed in both compartments and at significantly higher levels in HIV + ART compared to HIVneg. IL-17A transcripts were only detectable in SCB, with increased IL-17A levels in HIVneg compared to HIV + ART and negatively correlated with IL-32β mRNA levels. IL-32β/γ/e isoform mRNA were detected in HT-29 cells upon exposure to TNF-α, Poly I:C (TLR3 agonist), Flagellin (TLR-5 agonist) and HIV. IL-17A significantly decreased both IL-32 β/γ/e mRNA and cell-associated IL-32 protein levels induced upon TNF-α and Poly I:C triggering. Conclusions We document IL-32 isoforms abundant in the colon of ART-treated PLWH and reveal the capacity of the Th17 hallmark cytokine IL-17A to attenuate IL-32 overexpression in a model of inflamed IEC.

The identification of transmission clusters (TCs) of HIV-1 using phylogenetic analyses can provide insights into viral transmission network and help improve prevention strategies. We compared the use of partial HIV-1 envelope fragment of 1,070 bp with its loop 3 (108 bp) to determine its utility in inferring HIV-1 transmission clustering. Serum samples of recently (n = 106) and chronically (n = 156) HIV-1-infected patients with status confirmed were sequenced. HIV-1 envelope nucleotide-based phylogenetic analyses were used to infer HIV-1 TCs. Those were constructed using ClusterPickerGUI_1.2.3 considering a pairwise genetic distance of ≤10% threshold. Logistic regression analyses were used to examine the relationship between the demographic factors that were likely associated with HIV-1 clustering. Ninety-eight distinct consensus envelope sequences were subjected to phylogenetic analyses. Using a partial envelope fragment sequence, 42 sequences were grouped into 15 distinct small TCs while the V3 loop reproduces 10 clusters. The agreement between the partial envelope and the V3 loop fragments was significantly moderate with a Cohen's kappa (κ) coefficient of 0.59, p

Aim: Improvement of breast cancer (BrCa) control will be markedly supported by early detection. Owing to limitations of current diagnostic tools like mammography and ultrasound and lack of existing confirmed BrCa biomarkers, this study concerned the evaluation of some potential biomarkers and their combination in BrCa detection. Methods: Three hundred participant women; 200 with BrCa patients, 50 with benign breast diseases, and 50 healthy individuals were enrolled in this study. Serum levels of nuclear matrix protein-52 (NMP-52), collagen III, and matrix metalloproteinase-1 (MMP-1) were determined by ELISA. Results: Mean levels of NMP-52 (9.83±1.1 μg/ml), collagen III (22.6±3.2 μg/mL) and MMP-1 (3.6±0.3 μg/mL) in BrCa patients were significantly higher (P 2cm). Diagnostic scores combined these markers revealed valuable power (AUC=0.83, 78% sensitivity, 75% specificity) in BrCa diagnosis. This power is not markedly influenced in the detection of early tumor stages (Tis-T2), low grade (G1-G2), lesser tumor size ≤2 cm, and negative lymph nodes status (AUC=0.79, 0.74, 0.74, and 0.85, respectively). Conclusions: Combined use of NMP-52, collagen III, and MMP-1 can serve as a potential biomarker for BrCa diagnosis. This combination is likely to improve the clinical early tumor diagnosis.

Background: Currently, blood markers are noninvasive methods for the diagnosis of patients with colorectal cancer (CRC). We evaluated four biomarkers (Carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA19.9), collagen III, and metalloproteinase 1 (MMP-1)) and their combination as a substitute method to enhance diagnosis of CRC. Subjects and methods: one hundred ninety-five patients who had undergone colonoscopy examination were included in the study (135 CRC and 60 benign growths). Also, 45 healthy individuals were included. Multivariate discriminant analysis (MDA) and area under the receiver operating characteristic curve (AUC) were applied for evaluating the diagnostic power of single and their combination. Results: levels of collagen III, CEA, and CA 19.9 increased while MMP-1 decreased with the progression of CRC (stages, positive lymph node invasion, distant organ metastasis, and high grades) with a significant difference (P P < 0.0001). Combination of MMP-1, CEA, CA 19-9, and Collagen III yielded MC3 index had diagnostic power greater than every single marker could achieve alone. When differentiating colon cancer from benign growth, the AUC of MC3 index was 0.91 yielded 85.2% sensitivity and 86.7% specificity. Moreover, the MC3 index for patients with late stages, lymph node invasion, organ metastasis, and high-grade had AUC = 0.81, 0.82, 0.80, and 0.80 higher than CEA and CA19.9.Conclusion: MC3 index is can be used as an effective index for early detection of CRC.

HIV persists in latently infected CD4+ T cells during antiretroviral therapy (ART). Immune checkpoint molecules, including PD-1, are preferentially expressed at the surface of persistently infected cells. However, whether PD-1 plays a functional role in HIV latency and reservoir persistence remains unknown. Using CD4+ T cells from HIV-infected individuals, we show that the engagement of PD-1 inhibits viral production at the transcriptional level and abrogates T-cell receptor (TCR)-induced HIV reactivation in latently infected cells. Conversely, PD-1 blockade with the monoclonal antibody pembrolizumab enhances HIV production in combination with the latency reversing agent bryostatin without increasing T cell activation. Our results suggest that the administration of immune checkpoint blockers to HIV-infected individuals on ART may facilitate latency disruption. The immune checkpoint molecule PD-1 is expressed on a fraction of CD4+ T cells latently infected with HIV, but whether PD-1 plays a functional role in reservoir persistence remains unknown. Here, Fromentin et al. show that PD-1 blockade potentiates latency reversal ex vivo in CD4+ T cells from ART suppressed individuals.

BACKGROUND Despite the success of antiretroviral therapy (ART) to control viral replication, people living with HIV (PWH) have high levels of chronic systemic inflammation and immune dysregulation which drives accelerated co-morbidities including coronary artery disease (CAD). Regulatory T cells (Tregs) and ectonucleotidases CD39/CD73 are known to be athero-protective via their immunosuppressive and anti-inflammatory functions. DESIGN We assessed the dynamics of Treg subsets in ART-treated PWH with or without CAD vs. HIV-uninfected individuals. METHODS Blood specimens were obtained from 142 participants including ART-treated HIV-infected adults with (n = 43) or without CAD (n = 41), as well as HIV-uninfected controls with (n = 31) or without CAD (n = 27). CAD was determined by the presence of atherosclerotic features on computed tomography angiography of the coronary arteries performed on all study participants. Treg subsets frequencies were assessed by flow cytometry. RESULTS Regardless of statin treatment or ART regimen, HIV+CAD+ individuals had the highest total Treg frequencies and increased thymic generation and output of Tregs (Helios/CD31 expression), while athero-protective CD39+/CD73+ Tregs were significantly depleted in this group. Tregs from PWH had higher expression of CCR6/CXCR3 than uninfected individuals regardless of CAD, while in HIV+CAD+ individuals Tregs expressed the highest levels of CCR4, which limits their maintenance. The lowest levels of CD4+ and CD8+ T-cell immune activation has been observed in HIV+CAD+ within study groups. CONCLUSION ART-treated PWH with diagnosed CAD are characterized by profound alterations in populations of anti-inflammatory and athero-protective Treg subsets. These changes may contribute to atherosclerotic plaque formation and progression during chronic HIV infection in the ART era.

Background. The hospital environment, especially surfaces and medical devices, is a source of contamination for patients. Objective. This study carried out, to the best of our knowledge, for the first time at Taza Hospital in Morocco aimed to assess the microbiological quality of surfaces and medical devices in surgical departments and to evaluate the disinfection procedure in time and space. Methods. Samples were taken by swabbing after cleaning the hospital surface or medical device, to isolate and identify germs which were inoculated on semiselective culture media then identified by standard biochemical and physiological tests, using the analytical profile index (API) galleries. Moreover, the association rules extraction model between sites on the one hand and germs on the other hand was used for sampling. Results. The study showed that 83% of the samples have been contaminated after biocleaning. The most contaminated services have been men’s and women’s surgeries. 62% of isolated germs have been identified as Gram-positive bacteria, 29% as Gram-negative bacteria, and 9% as fungi. Concerning the association rules extraction model, a strong association between some contaminated sites and the presence of germ has been found, such as the association between wall and nightstand and door cuff, meaning that the wall and nightstand contamination is systematically linked to that of the door cuff. The disinfection procedure efficacy evaluation has enabled suggesting renewing it each 4 h. Conclusion. Microbiological monitoring of surfaces is necessary at hospital level through the use of the association rule extraction model, which is very important to optimize the sampling, cleaning, and disinfection site scenarios of the most contaminated ones.

Elite controllers (ECs) are people living with human immunodeficiency virus (HIV) who spontaneously control viral replication without antiretroviral therapy. We observed that elevated anti-cytomegalovirus (CMV) immunoglobulin G (IgG) levels correlated with annual CD4 T-cell count decay in ECs independently of age, sex, and human leukocyte antigen (HLA) type. Elevated anti-CMV titers may favor disease progression in ECs.

Background/aim Diabetes mellitus (DM) is a serious, chronic and epidemic disease. Its effective therapy with exogenous insulin places an overwhelming burden on the patient's lifestyle. Moreover, pancreatic islet transplantation is limited by the scarceness of donors and the need for chronic immunosuppression. Cell-based therapy is considered an alternative source of insulin-producing cells (IPCs); encapsulating such cellular grafts in immunoisolating devices would protect the graft from immune attack without the need for immunosuppression. Herein, we investigate the ability of TheraCyte capsule as an immunoisolating device to promote the maturation of differentiated rat bone marrow derived mesenchymal stem cells (BM-MSCs), transplanted subcutaneously to treat diabetic rats in comparison with intratesticular transplantation. Main methods Rat BM-MSC were differentiated into IPCs, and either encapsulated in TheraCyte capsules for subcutaneous transplantation or transplanted intratesticular into diabetic rats. Serum insulin, C-peptide & blood glucose levels of transplanted animals were monitored. Retrieved cells were further characterized by immunofluorescence staining and gene expression analysis. Key findings Differentiated rat BM-MSC were able to produce insulin in vitro, ameliorate hyperglycemia in vivo and survive for 6 months post transplantation. Transplanted cells induced higher levels of insulin and C-peptide, lower levels of blood glucose in the cured animals of both experimental groups. Gene expression revealed a further in vivo maturation of the implanted cells. Significance These data suggest that TheraCyte encapsulation of allogeneic differentiated stem cells are capable of reversing hyperglycemia, which holds a great promise as a new cell based, clinically applicable therapies for diabetes., Stem cells, Diabetes, Subcutaneous transplantation; Biological sciences; Cell biology; Biochemistry; Endocrinology; Regenerative medicine.

Aim: To study the potential use of nanoformulations of curcumin (CUR); CUR-loaded pluronic nanomicelles (CURnp1), and CUR-loaded poly(lactic-co-glycolic acid) nanoparticles (CURnp2) as antitumor agents in Ehrlich ascites carcinoma-bearing animals, and their mechanism of action. Materials & methods: CURnp1 and CURnp2 were prepared, characterized and tested against Ehrlich ascites carcinoma-bearing mice. Superoxide dismutase, catalase (CAT), glutathione, malondialdehyde, histopathological, immunohistochemical studies, cell cycle and caspase-3 were investigated. Results & conclusion: CURnp1 destroyed tumors via increasing superoxide dismutase, CAT and glutathione, decreasing malondialdehyde through inducing apoptosis by decreasing Ki-67 and Bcl2 expression and activating caspase-3 leading to inhibition of proliferation and cell cycle arrest with progression at G1/S phase. The study demonstrated for the first time superiority of CURnp1 over native CUR and CURnp2 as anticancer agents.

Background: HIV-1 transmitted/founder viruses (TF) are selected during the acute phase of infection from a multitude of virions present during transmission. They possess the capacity to establish infection and viral dissemination in a new host. Deciphering the discrete genetic determinant of infectivity in their envelope may provide clues for vaccine design. Methods: One hundred twenty-six clade B HIV-1 consensus envelope sequences from untreated acute and early infected individuals were compared to 105 sequences obtained from chronically infected individuals using next generation sequencing and molecular analyses. Results: We identified an envelope amino acid signature associated with TF viruses. They are more likely to have an isoleucine (I) in position 841 instead of an arginine (R). This mutation of R to I (R841I) in the gp41 cytoplasmic tail (gp41CT), specifically in lentivirus lytic peptides segment 1 (LLP-1), is significantly enriched compared to chronic viruses (OR = 0.2, 95% CI (0.09, 0.44), p = 0.00001). Conversely, a mutation of lysine (K) to isoleucine (I) located in position six (K6I) of the envelope signal peptide was selected by chronic viruses and compared to TF (OR = 3.26, 95% CI (1.76&ndash, 6.02), p = 0.0001). Conclusions: The highly conserved gp41 CT_ LLP-1 domain plays a major role in virus replication in mediating intracellular traffic and Env incorporation into virions in interacting with encoded matrix protein. The presence of an isoleucine in gp41 in the TF viruses&rsquo, envelope may sustain its role in the successful establishment of infection during the acute stage.

Early HIV-1 infection is characterized by enhanced tryptophan catabolism, which contributes to immune suppression and disease progression. However, the mechanism by which kynurenine, a tryptophan-related metabolite, induces immune suppression remains poorly understood. Herein, we show that the increased production of kynurenine correlates with defective interleukin-2 (IL-2) signaling in memory CD4 T cells from HIV-infected subjects. Defective IL-2 signaling in these subjects, which drives reduced protection from Fas-mediated apoptosis, was also associated with memory CD4 T-cell loss. Treatment of memory CD4 T cells with the concentration of kynurenine found in plasma inhibited IL-2 signaling through the production of reactive oxygen species. We further show that IL-2 signaling in memory CD4 T cells is improved by the antioxidant N -acetylcysteine. Early initiation of antiretroviral therapy restored the IL-2 response in memory CD4 T cells by reducing reactive oxygen species and kynurenine production. The study findings provide a kynurenine-dependent mechanism through IL-2 signaling for reduced CD4 T-cell survival, which can be reversed by early treatment initiation in HIV-1 infection. IMPORTANCE The persistence of functional memory CD4 T cells represents the basis for long-lasting immune protection in individuals after exposure to HIV-1. Unfortunately, primary HIV-1 infection results in the massive loss of these cells within weeks of infection, which is mainly driven by inflammation and massive infection by the virus. These new findings show that the enhanced production of kynurenine, a metabolite related to tryptophan catabolism, also impairs memory CD4 T-cell survival and interferes with IL-2 signaling early during HIV-1 infection.

Aim: This study aimed to evaluate, for the first time the potential use of a safe biocompatible nanoformulation of silymarin (SM) as antitumor agent and to provide its mechanism of action compared with native SM. Materials & methods: SM was loaded into pluronic nanomicelles and Ehrlich ascites carcinoma-tumor-bearing mice were used as experimental model. Biochemical parameters including SOD, CAT and GSH, lipid peroxidation biomarkers (MDA), histopathological, ultrastructural and immunohistochemical studies were applied on the Ehrlich ascites carcinoma cells. Furthermore, the cell cycle as well as caspase-3 were examined. Results & conclusion: Nanoformulated SM (SMnp) destroyed tumors via increasing SOD, CAT and GSH concomitant with decreasing MDA. Moreover, SMnp-induced apoptosis through decreasing Ki-67 and Bcl2 expression, along with the activation of caspase-3, leads to inhibition of proliferation and the arrest of ceel cycle progression at the G1/S phase. Electron microscopy studies presented the superiority of SMnp over native SM in causing mitochondrial and nuclear degeneration in cancer cells.

BACKGROUND Although established markers such as CEA and CA19-9 are important for diagnosing early stages of colon cancer, they are not ideal. Developing promising markers include cytokeratin 1 (CK1) and mucin-1 (MUC1), but the combined value of each of these markers is unclear. We therefore evaluated the value of a combined laboratory-based score of these four markers in the diagnosis of colon cancer. METHODS Two hundred patients who had undergone colonoscopic examination (150 colon cancer, 50 benign growths) were recruited. The study was controlled by 35 healthy subjects. CEA, CA19-9, CK1 and MUC1 were measured by ELISA and evaluated for cancer diagnosis using area under the receiver operating characteristic curve (AUC). RESULTS Serum levels of all four markers were increased in the order colon cancer > benign disease > healthy controls (p