Cytotoxic T Lymphocytes Research Articles

The immune responses elicited by six recombinant antigens of Mycoplasma hyopneumoniae in mice

Mycoplasma hyopneumoniae (M. hyopneumoniae) is the causative agent of swine enzootic pneumonia, resulting in substantial economic losses in global pig farming. Although vaccination is the primary strategy for controlling M. hyopneumoniae infection, current vaccines fall short in preventing transmission of this pathogen or protecting the body from secondary infection. This study aimed to assess the immunogenicity of six recombinant antigens (P97R1, P46, GAPDH, PdhA, DnaK, and EF-Tu) of M. hyopneumoniae through intramuscular immunization in mice. The results showed that the six antigens elicited high levels of serum IgG. Among them, P97R1, P46, PdhA, and DnaK stimulated robust antigen-specific IgA mucosal immune responses. CCK-8 assays revealed that both P97R1 and DnaK significantly increased the proliferation of mononuclear cells from spleen and lung, and DnaK also promoted the proliferation of blood mononuclear cells. Additionally, PdhA induced Th17-type immune response with a high level of IL-17 level in serum. Flow cytometry analysis indicated that P97R1 and PdhA increased the ratio of CD8+/CD4+ T lymphocyte, favoring cytotoxic T lymphocyte (CTL) immune responses. Notably, P97R1 immunization significantly decreased the percentages of CD4+ T cells while increased the percentages of CD8+ T cells. The present findings demonstrate that the candidate antigens P97R1, PdhA, and DnaK of M. hyopneumoniae induce specific humoral and mucosal immunity; P97R1 and DnaK also stimulated intense cellular immunity, and PdhA induced CTL and Th17-type immune responses. In conclusion, P97R1, PdhA, and DnaK emerge as potential candidate antigens for the future development of a more effective subunit vaccine against M. hyopneumoniae.

Transcription factor networks drive perforin activity in the anti-bacterial immune response of tilapia

Perforin, produced by natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), is one of the effectors of cell-mediated cytotoxicity (CMC) in vertebrates, playing a paramount role in killing target cells. However, whether and how perforin is involved in adaptive immune responses in early vertebrates remains unclear. Using Nile tilapia (Oreochromis niloticus) as a model, we investigated the characteristics of perforin in early vertebrates. Oreochromis niloticus perforin (OnPRF) possesses 2 conserved functional domains, membrane attack complex/perforin (MACPF) and protein kinase C conserved region 2 (C2) domains, although they share low amino acid sequence similarity with other homologs. OnPRF was widely expressed in various immune tissues and could respond to lymphocyte activation and T-cell activation in vitro at both the transcriptional and protein levels, indicating that it may be involved in adaptive immune responses. Furthermore, after infection with Edwardsiella piscicida and Aeromonas hydrophila, the mRNA and protein levels of OnPRF were significantly up-regulated within the adaptive immune response period. Additionally, we revealed that many transcription factors were involved in the transcriptional regulation of OnPRF, including p65, c-Fos, c-Jun, STAT1 and STAT4, and there was a synergy among these transcription factors. Overall, these findings demonstrate the involvement of OnPRF in T-cell activation and adaptive immune response in tilapia, thus providing new evidence for comprehending the evolution of immune response in early vertebrates.

Evaluating the Impact of Adjunctive Partial Cryoablation on Dual Checkpoint Inhibitor Immunotherapy Response in a Murine Model.

Purpose To evaluate the impact of adjunctive partial cryoablation on checkpoint inhibitor (CPI) immunotherapy response. Materials and Methods One hundred fifty-six mice (equal number of male and female animals) with dual-implanted tumor models were treated with dual CPI or a vehicle and randomized to treatment of a single tumor with partial cryoablation. Tumors were followed for 60 days following cryoablation for response assessment. In additional groups, the tumor microenvironment was characterized via flow cytometry, cytokine analysis, and immunohistochemistry. Statistical comparison was made between the different treatment groups regarding T-cell infiltration and activation characteristics within the noncryoablated tumor and cytokine levels within the partially ablated tumor. Additionally, qualitative assessment of T-cell activation within the cryoablated and noncryoablated tumors at immunofluorescence was carried out. Results At 60 days following treatment, CPI and adjunctive cryoablation-treated MC-38 mice had a significantly increased survival rate (79%) compared with mice treated with CPI alone (61%; P < .001). CT-26 mice also had an increased survival rate (57% vs 35%, respectively; P = .04). Following cryoablation, increases in inflammatory cytokines and chemokines within the treated tumors were observed. Flow cytometry of noncryoablated tumor showed increased CD8 T-cell activation. Immunofluorescence and histologic evaluation following cryoablation further demonstrated a robust CD8 T-cell and myeloid infiltrate. Conclusion Adjunctive cryoablation significantly increased the response to dual CPI in multiple cancer models at both partially ablated and distant (nonablated) tumor sites. Immune analysis suggests cryoablation promotes a vigorous immune response within the partially cryoablated tumor that increases activation of the adaptive immune system within distant tumor sites. Keywords: Cancer, Cryoablation, Checkpoint Inhibitor Immunotherapy, Tumor Response Supplemental material is available for this article. © RSNA, 2024.

Enhanced cancer cell proliferation and aggressive phenotype counterbalance in breast cancer with high BRCA1 gene expression.

While comprehensive research exists on the mutation of the DNA repair gene BRCA1, limited information is available regarding the clinical significance of BRCA1 gene expression. Given that cancer cell proliferation is aggrevated by DNA repair, we hypothesized that high BRCA1 gene expression breast cancer (BC) might be linked with aggressive tumor biology and poor clinical outcomes. The cohorts: The Cancer Genome Atlas (TCGA, n = 1069), METABRIC (n = 1903), and SCAN-B (n = 3273) were utilzed to obtain data of 6245 BC patients. BC patients without BRCA1 mutation exhibited higher BRCA1 expression, which was associated with DNA repair functionality. However, no such correlation was observed with BRCA2 expression. The association of high BRCA1 expression with cancer cell proliferation was evidenced by significant enrichment of cell proliferation-related gene sets, higher histological grade, and proliferation score. Furthermore, increased levels of homologous recombination deficiency, intratumoral heterogeneity, and altered fractions were associated with high BRCA1 expression. Moreover, BC with high BRCA1 expression exhibited reduced infiltration of dendritic cells and CD8 T-cells, while showing increased infiltration of Th1 cells. Surprisingly, BRCA1 expression was not associated with the survival of BC irrespective of the subtypes. Conversely, BC with low BRCA1 expression enriched cancer aggravating pathway gene sets, such as Cancer Stem Cell-related signaling (NOTCH and HEDGEHOG), Angiogenesis, Epithelial-Mesenchymal Transition, Inflammatory Response, and TGF-beta signaling. Despite being linked to heightened proliferation of cancer cells and unassertive phenotype, BRCA1 expression did not show any association with survival in BC.

Convection-enhanced delivery of [177Lu]Lu-labeled gold nanoparticles combined with anti-PD1 checkpoint immunotherapy improves the survival of immunocompetent C57BL/6J mice with orthotopic GL261 murine glioma tumors

IntroductionOur objective was to study convection enhanced delivery (CED) of 177Lu-labeled metal chelating polymer (MCP) conjugated to gold nanoparticles ([177Lu]Lu-MCP-AuNP) alone or combined with anti-PD1 immune checkpoint inhibition (ICI) for improving the survival of immunocompetent C57BL/6J mice with orthotopic GL261 murine glioma tumors. MethodsC57BL/6J mice with GL261 tumors were treated with [177Lu]Lu-MCP-AuNP (0.8 or 2.7 MBq; 4 × 1011 AuNP) alone or combined with anti-PD1 antibodies (200 μg i.p. every 2 d × 3 doses). Control mice received normal saline, non-radioactive MCP-AuNP or anti-PD1 antibodies. Kaplan-Meier median survival was estimated. T-cell infiltration into the brain was probed by flow cytometry. Toxicity was assessed by monitoring body weight and cognitive function tests [Object Location Test (OLT) and Novel Object Recognition Test (NORT)] and T2-weighted MRI of the brain, overall health and ex vivo histopathological examination of the brain. ResultsTreatment with [177Lu]Lu-MCP-AuNP (0.8 MBq) significantly increased median survival compared to MCP-AuNP (29 vs. 25 d; P = 0.007) or normal saline-treated mice (24 d; P < 0.001). Combining [177Lu]Lu-MCP-AuNP (0.8 MBq) with anti-PD1 antibodies increased median survival to 32 d (P < 0.0001 vs. normal saline). Increasing the mean amount of [177Lu]Lu-MCP-AuNP to 2.7 MBq and combining with anti-PD1 antibodies extended survival to at least 218 d in 5/9 mice. Increased CD8+ cytotoxic T-cells and decreased CD4+ helper T-cells were found in the brain vs. normal saline-treated mice. No weight loss (>20 %) was observed for treated or control mice. There was no change in cognitive function in mice treated with [177Lu]Lu-MCP-AuNP (0.8 MBq) alone or combined with anti-PD1 antibodies assessed by the OLT or NORT. T2-weighted MRI in mice treated with 2.7 MBq [177Lu]Lu-MCP-AuNP combined with anti-PD1 antibodies revealed edema, gliosis and ex vacuo dilatation of the ventricle proximal to the site of infusion. Histopathological examination of the brain revealed dilatation of the ventricle and gliosis proximal to the site of infusion but no radiation necrosis. MRI and histological analysis did not reveal tumor in the brain of these mice. Mice treated with 2.7 MBq [177Lu]Lu-MCP-AuNP combined with anti-PD1 antibodies did not demonstrate overall deleterious health effects. ConclusionsWe conclude that CED of [177Lu]Lu-MCP-AuNP combined with anti-PD1 checkpoint immunotherapy improved the survival of immunocompetent C67BL/6J mice with GL261 glioma tumors in the brain. Higher administered amounts of [177Lu]Lu-MCP-AuNP (2.7 MBq vs. 0.8 MBq) were most effective and yielded long-term survival. Advances in knowledge and implications for patient careThis study demonstrates that combining a locally-infused radiation nanomedicine, [177Lu]Lu-MCP-AuNP and anti-PD1 checkpoint immunotherapy improved the survival of mice with glioma tumors in the brain. In the future, this treatment may be useful to treat residual tumor at the surgical margins in patients with GBM to prevent local recurrence and improve survival.

Alternate MHC I antigen presentation pathways allow CD8+ T-cell recognition and killing of cancer cells in the absence of ß2M or TAP.

Major histocpmpatibilty complex class I (MHC I) antigen presentation allows CD8+ T cells to detect and eliminate cancerous or virally infected cells. The MHC I pathway is not essential for cell growth and viability and consequently cancers and viruses can evade control by CD8+ T cells by inactivating antigen presentation. In cancers, two common ways for this evasion are the loss of either the MHC I light chain (ß2M) or the cytosol-to-endoplasmic reticulum (ER) peptide transporter (TAP). ß2M-null cells are generally thought to lack the MHC I pathway because the MHC I heavy chain by itself lacks the proper conformation for peptide display. TAP-null cells are thought to have severely defective MHC I antigen presentation because they are incapable of supplying peptides from the cytosol to MHC I molecules in the ER. However, we have found that highly reactive memory CD8+ T cells could still recognize cells that completely lacked ß2M or TAP. This was at least in part because in TAPnull cells, the Sec62 component of the Sec61 translocon supported the transfer of cytosolic peptides into the ER. In ß2M-negative cells, free MHC I heavy chains were able to bind peptides and assume a conformation that was sufficiently recognized by CD8+ T cells. This process required ER chaperones and the peptide-loading complex. We found that these mechanisms supported antigen presentation at a level that was sufficient for memory CD8+ T cells to kill melanoma cells both in vitro and in tumor-bearing mice. The implications for tumor immunotherapy are discussed.

WWOX tuning of oleic acid signaling orchestrates immunosuppressive macrophage polarization and sensitizes hepatocellular carcinoma to immunotherapy

BackgroundImmune checkpoint inhibitors (ICIs) are therapeutically effective for hepatocellular carcinoma (HCC) but are individually selective. This study examined the role of specific common fragile sites (CFSs) related gene in HCC...

Research Progress of PD 1/PD L1 Inhibitors in the Treatment of Urological Tumors.

Immune checkpoint inhibitors (ICIs) offer significant advantages for the treatment of urologic tumors, enhancing the immune function of anti-tumor T cells by inhibiting PD-1 and PDL1 binding. They have been shown to be well tolerated and remarkably effective in clinical practice, offering hope to many patients who are not well treated with conventional drugs. Clinical trials in recent years have shown that anti-PD-1 and PD-L1 antibodies have good efficacy and safety in the treatment of urologic tumors. These antibodies can be applied to a variety of urologic tumors, such as bladder cancer, renal cell carcinoma, and prostate cancer. They have been approved for the first-line treatment or as an option for follow-up therapy. By blocking the PD-1/PD-L1 signaling pathway, ICIs can release immune functions that are suppressed by tumor cells and enhance T-cell killing, thereby inhibiting tumor growth and metastasis. This therapeutic approach has achieved encouraging efficacy and improved survival for many patients. Although ICIs have shown remarkable results in the treatment of urologic tumors, some problems remain, such as drug resistance and adverse effects in some patients. Therefore, further studies remain important to optimize treatment strategies and improve clinical response in patients. In conclusion, PD-1/PD-L1 signaling pathway blockers have important research advances for the treatment of urologic tumors. Their emergence brings new hope for patients who have poor outcomes with traditional drug therapy and provides new options for immunotherapy of urologic tumors. The purpose of this article is to review the research progress of PD-1 and PD-L1 signaling pathway blockers in urologic tumors in recent years.

CWF19L1 promotes T-cell cytotoxicity through the regulation of alternative splicing.

Enhancing host anti-tumor immunity is paramount for advancing cancer immunotherapy. In this study, we identify CWF19-like cell cycle control factor 1 (CWF19L1) as a novel splicing regulator that enhances T cell-mediated cytotoxicity. CWF19L1 interacts prominently with key splicing factors within the nucleus, including components of the U5 small nuclear ribonucleoprotein (snRNP) and the pre-mRNA processing factor 19 (PRPF19) complex. Deficiency of CWF19L1 disrupts alternative splicing of immune-related genes, resulting in diminished expression of cytotoxic molecules. Furthermore, CWF19L1 plays a critical role in promoting T cell-mediated anti-tumor responses by upregulating the expression of effector cytokines. Our findings unveil previously undocumented functions of CWF19L1 in alternative splicing and its involvement in the regulation of anti-tumor immunity, highlighting its potential as a therapeutic target for novel cancer immunotherapies.

Unravelling the Reasons Behind Limited Response to Anti-PD Therapy in ATC: A Comprehensive Evaluation of Tumor-Infiltrating Immune Cells and Checkpoints.

Inhibiting the immune checkpoint (ICP) PD-1 based on PD-L1 expression status has revolutionized the treatment of various cancers, yet its efficacy in anaplastic thyroid carcinoma (ATC) remains limited. The therapeutic response depends upon multiple factors, particularly the conduciveness of the tumor's immune milieu. This study comprehensively evaluated and classified ATC's immune microenvironment (IME) to elucidate the factors behind suboptimal response to anti-PD therapy. Utilizing multiplex-immunofluorescence and immunohistochemistry, we retrospectively analyzed 26 cases of ATC for expression of ICPs PD-L1, PD-1, CTLA4, TIM3, and Galectin-9 and tumor-infiltrating cytotoxic T lymphocytes (CTL)-the effector cells, the anti-tumor NK cells, the immune-inhibitory myeloid-derived suppressor (MDSC) and regulatory T (Treg) cells, and B lymphocytes. Most ATCs (65%) exhibited PD-L1 positivity, but only 31%, in addition, had abundant CTL (type I IME), a combination associated with a better response to ICP inhibition. Additionally, PD-1 expression levels on CTL were low/absent in most cases-a "target-missing" situation-unfavorable for an adequate therapeutic response. All but one ATC showed nuclear Galectin-9 expression. The documentation of nuclear expression of Galectin-9 akin to benign thyroid is a first, and its role in ATC pathobiology needs further elucidation. In addition to less abundant PD-1 expression on CTL, the presence of MDSC, Treg, and exhausted cytotoxic T lymphocytes in the immune milieu of ATC can contribute to anti-PD resistance. TIM3, the most frequently expressed ICP on CTL, followed by CTLA4, provides alternate therapeutic targets in ATC. The co-expression of multiple immune checkpoints is of great interest for ATC since these data also open the avenue for combination therapies.

Potential Strategies for Overcoming Drug Resistance Pathways Using Propolis and Its Polyphenolic/Flavonoid Compounds in Combination with Chemotherapy and Radiotherapy.

Conventional cancer treatments include surgical resection, chemotherapy, hyperthermia, immunotherapy, hormone therapy, and locally targeted therapies such as radiation therapy. Standard cancer therapies often require the use of multiple agents, which can activate nuclear factor kappa B (NF-κB) in tumor cells, leading to reduced cell death and increased drug resistance. Moreover, the use of multiple agents also contributes to added toxicity, resulting in poor treatment outcomes. Cancer cells gradually develop resistance to almost all chemotherapeutics through various mechanisms, such as drug efflux, alterations in drug metabolism and transport, changes in signal transduction pathways, enhanced DNA repair capacity, evasion of apoptosis, increased mutations, reactivation of drug targets, interaction with the cancer microenvironment, cancer cell-stroma interactions, epithelial-mesenchymal transition (EMT)-mediated chemoresistance, epigenetic modifications, metabolic alterations, and the effect of cancer stem cells (CSCs). Developing new strategies to improve chemotherapy sensitivity while minimizing side effects is essential for achieving better therapeutic outcomes and enhancing patients' quality of life. One promising approach involves combining conventional cancer treatments with propolis and its flavonoids. These natural compounds may enhance tumor response to treatment while reducing toxicity. Propolis and its components can sensitize cancer cells to chemotherapeutic agents, likely by inhibiting NF-κB activation, reprogramming tumor-associated macrophages (TAMs; an M2-like phenotype), and thereby reducing the release of matrix metalloproteinase (MMP)-9, cytokines, chemokines, and the vascular endothelial growth factor (VEGF). By reducing TAMs, propolis and its components may also overcome EMT-mediated chemoresistance, disrupt the crosstalk between macrophages and CSCs, inhibit the maintenance of stemness, and reverse acquired immunosuppression, thus promoting an antitumor response mediated by cytotoxic T-cells. This review highlights the potential of flavonoids to modulate the responsiveness of cancer to conventional treatment modalities. The evidence suggests that novel therapeutic strategies incorporating flavonoids could be developed to improve treatment outcomes. The positive effects of combining propolis with chemotherapeutics include reduced cytotoxicity to peripheral blood leukocytes, liver, and kidney cells. Therefore, polyphenolic/flavonoid components may hold potential for use in combination with chemotherapeutic agents in the clinical treatment of various types of cancers.

Evaluating peripheral blood lymphocyte subset composition and lipopolysaccharide-induced cytokine secretory activity in mononuclear leukocyte cultures from patients with febrile and meningeal forms of tick-borne encephalitis

Introduction.Multiple studies on immune response in patients with various clinical forms of tick-borne encephalitis (TBE) have shown conflicting results. The study aim was to estimate the changes in peripheral blood lymphocyte subset counts and activity of spontaneous and lipopolysaccharide (LPS)-stimulated cytokine production in the mononuclear leukocyte cultures in patients with febrile and meningeal acute TBE.Materials and methods.Groups 1 and 2 included 16 and 12 patients with febrile and meningeal acute TBE, respectively. The control group included 13 healthy donors. Hemogram and T-lymphocyte, T-helper cell, T-cytotoxic and NK cell counts were analyzed by flow cytometry at week 1 of the disease as well as the spontaneous and LPS-stimulated secretion levels of TNFα, IL-1β, IL-6, IL-10, IL-8, and MCP-1 were assessed by ELISA in the supernatants of mononuclear cell cultures twice: during hospitalization and two weeks later. Statistical analysis was performed by the Mann–Whitney U-test, and Wilcoxon test.Results.Group 2 demonstrated significant decrease in spontaneous and/or LPS-stimulated levels of proinflammatory cytokines IL-1β, IL-6, MCP-1, and TNFα, but showed higher IL-8 level as compared with Group 1. In addition, spontaneous and/or LPS-induced levels of IL-6 and TNFαin Group 2 did not significantly differ from the controls, which presumably also indicated the suppression of their production. In contrast, spontaneous and/or LPS-induced levels of IL-1β, IL-6, MCP-1, and TNFαin Group 1 were higher than in the controls. The spontaneous IL-10 level in the patients from both groups were higher than in the controls. Peripheral blood lymphocyte and T-cytotoxic T-lymphocyte counts in both groups of TBE patients were lower than in the controls. There was significant increase in neutrophil counts, decrease in NK cell count in Group 2 as compared to the patients with a milder febrile form.Conclusion.Meningeal acute TBE patients was presumably associated with inadequate immune response with NK cell deficiency, T-cell dysfunction, increased neutrophil count in the peripheral blood and impaired pro-inflammatory cytokine production related to innate immune response.

Cell-autonomous IL6ST activation suppresses prostate cancer development via STAT3/ARF/p53-driven senescence and confers an immune-active tumor microenvironment

BackgroundProstate cancer ranks as the second most frequently diagnosed cancer in men worldwide. Recent research highlights the crucial roles IL6ST-mediated signaling pathways play in the development and progression of various cancers, particularly through hyperactivated STAT3 signaling. However, the molecular programs mediated by IL6ST/STAT3 in prostate cancer are poorly understood.MethodsTo investigate the role of IL6ST signaling, we constitutively activated IL6ST signaling in the prostate epithelium of a Pten-deficient prostate cancer mouse model in vivo and examined IL6ST expression in large cohorts of prostate cancer patients. We complemented these data with in-depth transcriptomic and multiplex histopathological analyses.ResultsGenetic cell-autonomous activation of the IL6ST receptor in prostate epithelial cells triggers active STAT3 signaling and significantly reduces tumor growth in vivo. Mechanistically, genetic activation of IL6ST signaling mediates senescence via the STAT3/ARF/p53 axis and recruitment of cytotoxic T-cells, ultimately impeding tumor progression. In prostate cancer patients, high IL6ST mRNA expression levels correlate with better recurrence-free survival, increased senescence signals and a transition from an immune-cold to an immune-hot tumor.ConclusionsOur findings demonstrate a context-dependent role of IL6ST/STAT3 in carcinogenesis and a tumor-suppressive function in prostate cancer development by inducing senescence and immune cell attraction. We challenge the prevailing concept of blocking IL6ST/STAT3 signaling as a functional prostate cancer treatment and instead propose cell-autonomous IL6ST activation as a novel therapeutic strategy.

HIV disease progression among heterosexually-infected individuals before the introduction of universal ART in China: A linear mixed-effects model.

In 2016, China introduced universal antiretroviral therapy (ART) for all HIV-infected individuals regardless of CD4 cell count. However, the natural history and rate of CD4 count decline among heterosexually-infected individuals remain uncharacterized. Analyzing national surveillance data can address this gap and shed light on the pathogenesis of HIV in this population. We used a linear mixed-effects model to assess CD4 trajectory over time before ART initiation and estimated the median time from HIV seroconversion to reaching CD4 thresholds of < 500, < 350, and < 200 cell/mm3. From the Chinese HIV/AIDS Comprehensive Response Information Management System, 59,085 eligible individuals were identified, with 113 having data to estimate the date of HIV seroconversion. The linear mixed-effects models estimated an intercept of 23.64 (95% confidence interval [CI]: 22.41 to 24.87) and a slope of -1.32 (95% CI: -1.34 to -1.30) for males, and an intercept of 22.70 (95% CI: 21.00 to 24.40) and a slope of -1.29 (95% CI: -1.31 to -1.27) for females. The estimated median times from HIV seroconversion to reaching CD4 count thresholds of < 500, < 350, < 200 cells/mm3 were 0.97, 3.74, and 7.20 years for males, and 0.26, 3.09, and 6.48 years for females, respectively. Males consistently took longer to reach these CD4 count thresholds compared to females of the same age group. Older individuals (≥ 40 years) reached CD4 thresholds faster than younger individuals (15-29 years), indicating more rapid disease progression in older people living with HIV.

Prevalence and predictors of precancerous cervical lesions among women living with HIV in Libreville, Gabon

BackgroundHIV-infected women are at an increased risk of developing precancerous cervical lesions (PCL) than non-infected women. In Gabon, no data exists on the prevalence of PCL among women living with HIV. The aim of this study was to assess the prevalence and risk factors associated with the development of PCL among HIV-positive women in Libreville, Gabon.MethodologiesThis was a retrospective study carried out within the Gynecology and Obstetrics Department of University Hospital Center of Libreville (CHUL) from January to August 2016. It included women registered at the HIV Clinic of Nkembo, and screened for PCL or cervical cancer (CC). Descriptive statistics were used to characterize sociodemographic data and the prevalence of PCL. The chi square and odd-ratio tests were used to evaluate the associations between PCL, CD4 count, antiretroviral use, age at first sexual intercourse, number of sexual partner tobacco, and contraception use.ResultsAmong the 115 HIV-positive women recruited, 33 (28.70%; SD ± 0.45) were diagnosed with PCL. 79.1% of them were on antiretroviral therapy (ART), and the mean CD4 cell count value was 411.74 cells/mm3 (SD ± 241.77). Being on ART, age, number of sexual partners, contraceptive use and smoking were not risk-factors linked with the development of PCL. CD4 cell count was the only associated risk-factors (p-value: 0.02).ConclusionThe incidence of PCL among HIV-infected is high in Libreville, Gabon, especially among those with baseline CD4 counts < 200 cells/mm3. This study recommends screening for cervical cancer for all HIV-infected women.

Current Trends in HIV Infection in the Republic of Crimea

The aim of this study was to analyse the trends in HIV infection, including diagnostic ones, in the Republic of Crimea in the period of 2014–2023. The source of data for this study was various statistical forms and reports. The findings revealed a significant downward trend in HIV incidence and a significant upward trend in HIV prevalence. The mortality rate was stable. The coverage of HIV testing and antiretroviral therapy increased over time. The number of patients with a suppressed viral load in the Republic fluctuated in different years of observation and reached 81% in 2023. In the second part of this study, we analysed the demographic and clinical laboratory characteristics of newly diagnosed patients with HIV. A predominance of men was noted. The proportion of injection drug users (IDUs) decreased, and the proportion of new HIV infection cases through heterosexual contacts increased. An increase in the median age of patients was also noted. Analysis of CD4 cell counts revealed significant differences between subgroups by gender, age, and route of infection. The longest time to disease detection was typical for IDUs. A comprehensive assessment of HIV infection trends in Crimea allows us to evaluate the effectiveness of measures and decisions taken on the issue of HIV infection.

Prevalence, Risk Factors, and Clinical Profiles of Hepatitis D Virus in Nigeria: A Systematic Review, 2009–2024

Background: The World Health Organization (WHO) recommends hepatitis D virus (HDV) screening among hepatitis B virus (HBV) infected individuals, with a focus on priority populations in resource-limited settings like Nigeria. HDV infection is a growing public health challenge, particularly among individuals with chronic hepatitis B virus (HBV) infection. HDV accelerates liver disease progression and significantly increases the risk of cirrhosis and hepatocellular carcinoma. Despite this, the epidemiology of HDV in Nigeria remains inadequately documented. This scoping review critically evaluates the prevalence, risk factors, and clinical outcomes of HDV co-infection among HBV patients in Nigeria. Method: We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The review included observational cross-sectional studies published between 2009 and 2024. We focused on studies that used Immunoglobulin G (IgG) antibody testing or RNA-based diagnostics to assess HDV prevalence. We included PubMed, Google Scholar, and Dimensions databases due to their broad indexing and coverage of peer-reviewed articles and accessibility. We screened the studies for their relevance to HDV prevalence, risk factors, and clinical outcomes, while excluding those that only tested for IgM or HDV antigen. Eleven studies, with a combined sample size of 2308 participants, were included in the final analysis. We performed a narrative synthesis of the findings, considering geographic, gender, and age-based variations in HDV prevalence and clinical impact. Results: HDV prevalence among HBV-infected individuals in Nigeria ranged from 2.0% to 31.6%. The highest prevalence was reported in the Southwest (31.6%) among malaria patients, while lower rates were observed in the Southeast (2.8%). Prevalence was higher in males, particularly those aged 21–30 years in the Southwest and 31–40 years in other regions. RNA-based testing provided more accurate data on active viremia, with viremic HDV prevalence rates ranging from 3.2% to 16%. Triple infection with HIV/HBV/HDV was associated with significantly lower CD4+ cell counts and worse clinical outcomes, including elevated liver enzymes and rapid progression to liver cancer. Key risk factors for HDV co-infection included multiple sexual partners, sharing of needles, and unsafe medical practices. Co-infected patients demonstrated worse clinical outcomes, such as elevated liver enzymes, decompensated cirrhosis, and higher rates of hepatocellular carcinoma. Conclusions: Our review underscores the urgent need for routine HDV screening among HBV patients in Nigeria, especially given the severe clinical consequences of co-infection. The recent WHO guidelines recommending HDV screening align with our findings, which emphasize the importance of RNA-based HDV testing among HBV-positive patients to improve diagnostic accuracy. Public health efforts should prioritize tailored interventions based on geographic, age, and gender disparities in HDV prevalence. Triple infection with HIV/HBV/HDV requires integrated care models to address both immune suppressions as indicated by diminished CD4 cell count and liver disease progression, as these patients face worse outcomes. Targeted HDV screening in mostly affected demographics and geographies and improved Nigeria capacity for cheaper HDV RNA/PCR diagnostics can reduce liver-related morbidity and mortality caused by HBV, which can be worsened and accelerated by HDV coinfection.

Characterising HIV-Indicator conditions among two nationwide long-term cohorts of people living with HIV in Germany (1999-2023).

Information about occurrence and affected groups of symptoms/diagnoses indicative of an HIV infection (so-called HIV indicator conditions; HIV-ICs) is lacking. We analyse HIV-IC incidence, transmission risks and immune status among people living with HIV (PLWH) antiretroviral therapy (ART) naive. Diagnoses reported for ART-naive PLWH from two multicentre observational, prospective cohort studies between 1999-2023 were analysed. Incidence rates per 1,000 person-years (PYs) were calculated for the overall study period and time periods defined by ART treatment recommendations. For further description, CD4 counts around HIV-IC diagnosis (+ -30days) and HIV-transmission routes were collected. In total 15,940 diagnoses of 18,534 PLWH in Germany were included. Of those 81% were male (median age: 36years) and 56% reported being men, who have sex with men as the likely HIV-transmission route. Incidence rates varied between the different HIV-ICs. Syphilis had the highest incidence rate (34 per 1,000 PYs; 95% confidence interval [CI] 29-40) for sexually transmitted infections (STIs), hepatitis B was highest for viral hepatitis diagnoses (18 per 1,000 PYs; 95% CI 17-20); according to CDC-classification herpes zoster for HIV-associated diagnoses (22 per 1,000; 95% CI 20-24) and candidiasis for AIDS-defining diagnoses (30 per 1,000 PYs; 95% CI 29-32). Most PLWH with HIV-ICs (hepatitis, HIV-associated diagnoses and AIDS-defining conditions) had CD4 cell counts < 350. This analysis characterizes HIV-ICs regarding the incidence, HIV-transmission route and patients' immune status. The results underline the importance of HIV-IC-based screening to detect PLWH with already partially impaired immune status and in need of timely ART initiation.

In Silico Development of a Multi-Epitope Subunit Vaccine against Bluetongue Virus in Ovis aries Using Immunoinformatics

The bluetongue virus (BTV), transmitted by biting midges, poses a significant threat to livestock globally. This orbivirus induces bluetongue disease, leading to substantial economic losses in the agricultural sector. The current control measures have limitations, necessitating the development of novel, efficient vaccines. In this study, an immunoinformatics approach is employed to design a multi-epitope subunit vaccine for Ovis aries targeting six BTV serotypes. Focusing on the VP2 capsid protein, the vaccine incorporates B-cell, helper-T lymphocytes (HTL), and cytotoxic T-cell lymphocytes (CTL) epitopes. Molecular docking reveals stable interactions with TLR2 and TLR4 receptors, suggesting the stability of the complex, indicating the potential viability of the multi-epitope vaccine. The computational approach offers a rapid and tailored strategy for vaccine development, highlighting potential efficacy and safety against BTV outbreaks. This work contributes to understanding BTV and presents a promising avenue for effective control.

Evaluation of Right Ventricular Diastolic Function among HIV-1-Infected Patients on Highly Active Antiretroviral Therapy and its Relationship with CD4 Cell Count and Viral Load

Abstract Context: With the introduction of highly active antiretroviral therapy, human immunodeficiency virus (HIV) patients live longer and therefore develop complications such as cardiovascular diseases. The prevalence of left ventricular diastolic dysfunction among HIV-infected patients ranges from 2.7% to 64%. Data on right ventricular diastolic function among HIV-infected patients in our region of northeastern Nigeria are lacking. Aims: We therefore assessed right ventricular diastolic function among HIV-infected patients on highly active antiretroviral therapy (HAART). Materials and Methods: This cross-sectional study was conducted among HIV-infected patients receiving HAART at the Federal Medical Centre Nguru, Yobe State, Northeastern Nigeria. Tricuspid flow E/A ratio, right ventricular deceleration time, and tissue Doppler E/e’ waves were used to assess the right ventricular diastolic function. Results: One hundred and seven subjects were recruited into the study comprising 70 (65.4%) females and 37 (34.6%) males. The prevalence of right ventricular diastolic dysfunction is 12.15%. CD4 cell count correlated positively with right ventricular deceleration time and negatively with tricuspid E/A ratio. Viral load correlated positively with the tricuspid E/A ratio and negatively with the tricuspid E/e ratio and right ventricular deceleration time. Conclusion: Right ventricular diastolic dysfunction is not uncommon among HIV-infected patients in northeastern Nigeria; its prevalence was found to be 12.15%, and there was a significant positive correlation between right ventricular deceleration time and CD4 cell count and a significant negative correlation between right ventricular deceleration time and viral load, suggesting that lower CD4 cell count and higher viral load are associated with worsening right ventricular diastolic function.