Therapeutic Effects of Tretinoin and Caffeine-Treated Bone Marrow-Derived Mesenchymal Stem Cell on Immunological Features of Ulcerative Colitis: An Animal Model Study.

Background: Ulcerative colitis (UC) is one of the inflammatory gastrointestinal diseases. It causes irritation, inflammation, and ulcers in the digestive tract. UC is distinguished clinically by abdominal and rectal pain and intestinal secretion abnormalities. Mesenchymal stem cell (MSC) therapy could be the underlying treatment for UC. This study aimed to compare the results of MSC therapy with tretinoin and caffeine in an animal model. Materials and Methods: Sixty male BALB/c mice were randomly divided into six equal groups. Five groups were exposed to acetic acid-induced colitis, and one healthy negative control group was designed. The positive control group was UC-induced mouse model with no treatment. Besides, treatment groups were MSCs (n = 2×106) that received tretinoin and caffeine. The treatment group was given mesalazine orally. The decision to begin treatment was taken after monitoring the symptoms of the UC. Results: MSCs, tretinoin, and caffeine-treated MSCs significantly decrease inflammatory cytokines (interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α) and inflammatory mediators (myeloperoxidase (MPO) and nitric oxide (NO)) compared with the positive control group. However, the alleviated effects of tretinoin-treated MSCs significantly were more than those of MSCs and caffeine-treated MSCs. Conclusion: MSC therapy is an effective option for UC and can prevent disease progression. The results represented a high developmental rate and simple cell application of MSC therapy in UC patients. Also, MSC therapy's ability for immunomodulation is strengthened by drugs that improve their microenvironment by binding to their receptors.

Investigating the potential of oncolytic viruses for cancer treatment via MSC delivery.

Mesenchymal stem cells (MSCs) have attracted considerable interest as a promising approach for cancer treatment due to their ability to undergo tumor-trophic migration. MSCs possess the unique ability to selectively migrate to tumors, making them an excellent candidate for targeted delivery of oncolytic viruses (OVs) to treat isolated tumors and metastatic malignancies. OVs have attracted attention as a potential treatment for cancer due to their ability to selectively infect and destroy tumor cells while sparing normal cells. In addition, OVs can induce immunogenic cell death and contain curative transgenes in their genome, making them an attractive candidate for cancer treatment in combination with immunotherapies. In combination with MSCs, OVs can modulate the tumor microenvironment and trigger anti-tumor immune responses, making MSC-releasing OVs a promising approach for cancer treatment. This study reviews researches on the use of MSC-released OVs as a novel method for treating cancer. Video Abstract.

Viral Vectors, Exosomes, and Vexosomes: Potential armamentarium for delivering CRISPR/Cas to cancer cells.

The underlying cause of cancer is genetic disruption, so gene editing technologies, particularly CRISPR/Cas systems can be used to go against cancer. The field of gene therapy has undergone many transitions over its 40-year history. Despite its many successes, it has also suffered many failures in the battle against malignancies, causing really adverse effects instead of therapeutic outcomes. At the tip of this double-edged sword are viral and non-viral-based vectors, which have profoundly transformed the way scientists and clinicians develop therapeutic platforms. Viruses such as lentivirus, adenovirus, and adeno-associated viruses are the most common viral vectors used for delivering the CRISPR/Cas system into human cells. In addition, among non-viral vectors, exosomes, especially tumor-derived exosomes (TDEs), have proven to be quite effective at delivering this gene editing tool. The combined use of viral vectors and exosomes, called vexosomes, seems to be a solution to overcoming the obstacles of both delivery systems.

Human Hematopoietic Stem Cells Co-cultured in 3D with Stromal Support to Optimize Lentiviral Vector-mediated Gene Transduction.

HSC transplantation (HSCT) has emerged as a promising treatment option for hematological and immunological disorders. Unfortunately, many viral vectors are inefficient at transduction, limiting the number of cells available for gene therapy in cord blood HSC transplantation. Combining ex vivo expansion and genetic manipulation of cord blood cells is a potential gene therapy approach. We present a 3D co-culture method using a demineralized bone matrix scaffold to optimize lentiviral vector-mediated gene transduction. pLenti-III-miR-GFP-has-miR-124 was transduced into cord blood HSCs. Transduced CD34 + cells co-cultured on the stromal layer for 72 h under cytokine-free conditions. We performed flow cytometry, colony assays, real-time polymerase chain reaction, and SEM morphological analysis. Seventy-two hours after transduction, when pLentiIII-miR-GFP-has-miR-124 and control vector-transduced expanded cord blood HSCs were compared to non-transduced expanded cord blood HSCs, the findings revealed 15 ± 3.04 and 55 ± 3.05-fold increases in miR-124 mRNA expression, respectively. Compared to a control culture on the same day, the expansion of CD34+, CD38-HSCs in 3D culture increased 544 ± 31.09 fold. This result demonstrated that the 3D-culture system could emerge as a novel approach to overcoming the current limitations of cord blood HSC transduction. In the future, this research could be applied in a therapeutic setting.

Design of a multi-epitope-based vaccine consisted of immunodominant epitopes of structural proteins of SARS-CoV-2 using immunoinformatics approach.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown rapid global spread and has resulted in a significant death toll worldwide. In this study, we aimed to design a multi-epitope vaccine against SARS-CoV-2 based on structural proteins S, M, N, and E. We identified B- and T-cell epitopes and then the antigenicity, toxicity, allergenicity, and similarity of predicted epitopes were analyzed. T-cell epitopes were docked with corresponding HLA alleles. Consequently, the selected T- and B-cell epitopes were included in the final construct. All selected epitopes were connected with different linkers and flagellin and pan-HLA DR binding epitopes (PADRE) as an adjuvant were used in the vaccine construct. Furthermore, molecular docking was used to evaluate the complex between the final vaccine construct and two alleles, HLA-A*02:01 and HLA-DRB1*01:01. Finally, codons were optimized for in silico cloning into pET28a(+) vector using SnapGene. The final vaccine construct comprised 11 CTL, HTL, and B-cell epitopes corresponding to 394 amino acid residues. In silico evaluation showed that the designed vaccine might potentially promote an immune response. Further in vivo preclinical and clinical testing is required to determine the safety and efficacy of the designed vaccine.

Combined extract of heated TC1, a heat-killed preparation of Lactobacillus casei and alpha-galactosyl ceramide in a mouse model of cervical cancer.

BACKGROUND: Nowadays, cancer is the leading cause of death among threats to humanity, necessitating prompt action and preparation. Cervical cancer is one of the most common cancers in women and is currently treated with surgery, radiation, chemotherapy, and immunotherapy, among other treatments. Current oncology approaches focused on the simultaneous development of safe and effective cancer multi-agent therapies. The present study aimed to evaluate the effects of a combined extracts of heated TC1, a heat-killed preparation of Lactobacillus casei, and alpha-galactosyl ceramide (α-GalCer) in a mouse model of cervical cancer. MATERIAL AND METHODS: Cervical cancer in the mouse model was prepared by TC1 cells subcutaneous injection into the left flank of female C57BL/6 mouse aged 6-8 weeks (n = 80). After the appearance of the palpable tumor, the mice with cervical cancer were randomly devoted to 8 (ten-member) groups. The mice in some groups were treated with PBS, TC1 cell extract, L. casei extract, α-GalCer, and a combination of the mentioned treatments. Then, they were evaluated the splenocytes proliferation, lactate dehydrogenase production and nitric oxide. Moreover, IL-4, IFN-γ, and TGF-ß cytokine levels of splenocytes supernatant the mice were measured. In all evaluations, a statistical difference of less than 0.05 (P ˂ 0.05) was considered as a significant level. RESULT: The findings revealed that the combination therapy group (heated TC1 cell and L. casei extracts with α-GalCer) significantly increases the splenocytes proliferation (MTT) (0.358 ± 0.04 OD), LDH production (45.9 ± 2.3 U/L), NO rate (38.4 ± 2.8 µM), and IFN-γ cytokine level (46.6 ± 3.7 pg/ml) (P < 0.05). Also, observes a significantly reduces the production of IL-4 (11.6 ± 2.5 pg/ml) and TGF-ß cytokines levels (7.8 ± 2.5 pg/ml) (P < 0.05) in comparison to the control group. CONCLUSION: The study showed that combination therapy of L. casei and α-GalCer is an efficient treatment for cervical cancer in the mouse model.

Advances in early diagnosis of cervical cancer based on biosensors.

Human papillomavirus (HPV) is a causative agent of cervical cancer among women worldwide. Serological and molecular tests are commonly used to detect and identify HPV, but all the detection methods for HPV have some limitations. Nowadays, considerable advancements in nanosensors have enabled monitoring of hybridization procedures dynamically for HPV detection. Biosensors, as effective, quick, economical, and highly sensitive tools, can be used in the diagnosis of HPV as an alternative technique instead of other detection methods. Biosensor detection methods of HPV in use from 2000 to 2021 were investigated using several databases such as Google Scholar, Scopus, PubMed, and the Scientific Information Database. Furthermore, a manual search of the references of the retrieved articles was performed. On analyzing the most recently developed biosensors for HPV identification, we observed that three biosensor systems, electrochemical, optical, and piezoelectric systems, are the main transducers used in the development of HPV biosensors. The aim of this review is to examine recent research on biosensors for the detection of HPV and perform a comparison with other diagnostic methods. Considering the importance of rapid HPV detection in the control of infection and development of public health measures, improvement of biosensors as an economical and quick method can be very useful in the diagnosis of HPV.

Overview of the pre-clinical and clinical studies about the use of CAR-T cell therapy of cancer combined with oncolytic viruses.

BACKGROUND: Cancer is one of the critical issues of the global health system with a high mortality rate even with the available therapies, so using novel therapeutic approaches to reduce the mortality rate and increase the quality of life is sensed more than ever. MAIN BODY: CAR-T cell therapy and oncolytic viruses are innovative cancer therapeutic approaches with fewer complications than common treatments such as chemotherapy and radiotherapy and significantly improve the quality of life. Oncolytic viruses can selectively proliferate in the cancer cells and destroy them. The specificity of oncolytic viruses potentially maintains the normal cells and tissues intact. T-cells are genetically manipulated and armed against the specific antigens of the tumor cells in CAR-T cell therapy. Eventually, they are returned to the body and act against the tumor cells. Nowadays, virology and oncology researchers intend to improve the efficacy of immunotherapy by utilizing CAR-T cells in combination with oncolytic viruses. CONCLUSION: Using CAR-T cells along with oncolytic viruses can enhance the efficacy of CAR-T cell therapy in destroying the solid tumors, increasing the permeability of the tumor cells for T-cells, reducing the disturbing effects of the immune system, and increasing the success chance in the treatment of this hazardous disease. In recent years, significant progress has been achieved in using oncolytic viruses alone and in combination with other therapeutic approaches such as CAR-T cell therapy in pre-clinical and clinical investigations. This principle necessitates a deeper consideration of these treatment strategies. This review intends to curtly investigate each of these therapeutic methods, lonely and in combination form. We will also point to the pre-clinical and clinical studies about the use of CAR-T cell therapy combined with oncolytic viruses.

A comparative study of laboratory findings in PCR-positive and PCR-negative COVID-19 hospitalized patients.

INTRODUCTION: Given the many misconceptions in terms of both diagnosis and treatment, SARS-CoV-2 continues to infect and victimize. Notwithstanding molecular testing is the gold standard method of in vitro diagnostic, the often long-waiting time, as well as false-negative results are daunting challenges facing us. In this study, we aimed to report the diagnostic value of laboratory findings in COVID-19 patients, with an extensive focus on the differences between PCR-positive and PCR-negative cases. PATIENTS AND METHODS: We did a retrospective single-centre study on a large cohort of 1546 COVID-19 patients in Tehran, Iran. Based on clinical symptoms, chest CTs were performed for all the patients. Also, molecular testing of swab specimens was also performed for 1450 cases. RESULTS: All the data on laboratory results were retrospectively extracted from medical records. Of the 1546 patients, 1040 (67.5%) were male and 506 (32.5%) were female with the mean age of 55.67. On admission, 31.4% of the whole study population displayed lymphopenia and 38.9% showed neutrophilia. Decreased hemoglobin and mild thrombocytopenia were also found in 40% and 18.6% of cases, respectively. Elevated lactate dehydrogenase in nearly 75% of COVID-19 cases was the most common alteration amongst biochemical parameters which together with increased ESR and CRP could serve as diagnostic markers in SARS-CoV-2 infection. Of the 1450 patients with a PCR result, 439 (28.3%) were PCR-negative and 1011 (65.3%) were PCR-positive. Notably, lymphopenia and increased AST were higher in the PCR-positive group than their negative counterparts. Albeit being in the normal range, a significant decrease in the number of monocytes was also evident in the PCR-positive cases. CONCLUSIONS: As far we are aware, this is the first time that we reported a comprehensive exploration of laboratory characteristics of a large cohort of hospitalized COVID-19 patients from Iran, hoping that these data will cast more light on the diagnostic significance of these parameters.

Combination therapy with CAR T cells and oncolytic viruses: a new era in cancer immunotherapy.

Chimeric antigen receptor (CAR) T-cell therapy is an encouraging and fast-growing platform used for the treatment of various types of tumors in human body. Despite the recent success of CAR T-cell therapy in hematologic malignancies, especially in B-cell lymphoma and acute lymphoblastic leukemia, the application of this treatment approach in solid tumors faced several obstacles resulted from the heterogeneous expression of antigens as well as the induction of immunosuppressive tumor microenvironment. Oncolytic virotherapy (OV) is a new cancer treatment modality by the use of competent or genetically engineered viruses to replicate in tumor cells selectively. OVs represent potential candidates to synergize the current setbacks of CAR T-cell application in solid tumors and then and overcome them. As well, the application of OVs gives researches the ability to engineer the virus with payloads in the way that it selectively deliver a specific therapeutic agents in tumor milieu to reinforce the cytotoxic activity of CAR T cells. Herein, we made a comprehensive review on the outcomes resulted from the combination of CAR T-cell immunotherapy and oncolytic virotherapy for the treatment of solid cancers. In the current study, we also provided brief details on some challenges that remained in this field and attempted to shed a little light on the future perspectives.

Therapeutic potential of CAR T cell in malignancies: A scoping review.

Although tremendous advancements in cancer therapy over the last several years, cancer still is a complex illness to cure. Traditional cancer treatments, including chemotherapy, radiotherapy, and surgery, have a poor therapeutic effect, emphasizing the significance of employing innovative treatments like activated cell therapy. Chimeric antigen receptor T cell is one of the most prevalent types of activated cell therapy have been developed to direct T lymphocytes toward cancers (CAR-T cells). CAR-T cells therapy has illustrated poor impact versus solid tumors despite the remarkable success in patients suffering from hematological malignancies. CAR-T cells must overcome various hurdles to obtain full responses to solid tumors, including growth, stability, trafficking, and destiny inside tumors. As a result, novel treatment methods will entail overcoming the challenges that CAR-T cells face in solid tumors. The use of CAR-T cells in combination with other therapeutic approaches such as chemotherapy, radiotherapy, immuno-checkpoint inhibitors, and oncolytic viruses can promote the effectiveness of CAR-T cell therapy for the treatment of solid tumors. However, more research is needed to determine the safety and effectiveness of these therapies. CAR-T cell treatment success rates vary by type of disease, but are predicted to reach up to 90% in patients with leukemia. However, since this kind of immunotherapy is still in its infancy, there is much to learn about its efficacy. This review provided an in-depth examination of CAR-T cell therapy and its success and failure as a cancer treatment approach. We also discuss combination therapies with CAR-T Cell.

Droplet digital PCR of viral DNA/RNA, current progress, challenges, and future perspectives.

High-throughput droplet-based digital PCR (ddPCR) is a refinement of the conventional polymerase chain reaction (PCR) methods. In ddPCR, DNA/RNA is encapsulated stochastically inside the microdroplets as reaction chambers. A small percentage of the reaction chamber contains one or fewer copies of the DNA or RNA. After PCR amplification, concentrations are determined based on the proportion of nonfluorescent partitions through the Poisson distribution. Some of the main features of ddPCR include high sensitivity and specificity, absolute quantification without a standard curve, high reproducibility, good tolerance to PCR inhibitor, and high efficacy compared to conventional molecular methods. These advantages make ddPCR a valuable addition to the virologist's toolbox. The following review outlines the recent technological advances in ddPCR methods and their applications in viral identification.

Oncolytic Viruses and Cancer, Do You Know the Main Mechanism?

The global rate of cancer has increased in recent years, and cancer is still a threat to human health. Recent developments in cancer treatment have yielded the understanding that viruses have a high potential in cancer treatment. Using oncolytic viruses (OVs) is a promising approach in the treatment of malignant tumors. OVs can achieve their targeted treatment effects through selective cell death and induction of specific antitumor immunity. Targeting tumors and the mechanism for killing cancer cells are among the critical roles of OVs. Therefore, evaluating OVs and understanding their precise mechanisms of action can be beneficial in cancer therapy. This review study aimed to evaluate OVs and the mechanisms of their effects on cancer cells.

P16INK4A Immunohistochemistry as a Gold Standard for Cervical Cancer and Precursor Lesions Screening.

BACKGROUND: High-risk (HR) Human papillomaviruses (HPVs) are known as the main factors implicated in the pathogenesis of cervical preinvasive and invasive lesions. Therefore, the presence or absence of HR-HPV can be followed for the prognosis of low-grade and high-grade squamous intraepithelial lesions. Since the overexpression of p16INK4a protein depends on the presence of transcriptionally-active HPV, and due to its availability and simple interpretation, it may be considered as a proper marker to diagnose cervical cancer. METHODS: An immunohistochemical analysis of p16INK4a was performed in 72 cervical tissue specimens at Imam Khomeini Complex Hospital (Tehran, Iran) from 2016 to 2018. The performance parameters were calculated and compared using receiving operating characteristics curve (ROC) details. RESULTS: p16INK4a is significantly up-regulated in the cervical cancer samples in comparison with that in normal samples. Moreover, the ROC data showed the potential ability of p16INK4a under determined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. The molecular typing disclosed the attendance of HPV DNA in 44.4% of cases (32/72) with a predominance of HPV type 16. CONCLUSION: The molecular biomarker p16INK4a can be a good candidate for the early diagnosis and prognosis of cervical cancer in HPV-infected patients. Considering the increase in the expression level of p16INK4a in cancer and precancer tissues, p16INK4a may be used for early detection of cervical cancer.

Comparison of Snail1, ZEB1, E-Cadherin Expression Levels in HPV-Induced Cervical Cancer.

BACKGROUND: Molecular profiling techniques are the rapid detection of biomarkers in the human papillomavirus (HPV) infected cells. We aimed to measure the expression level of three cell factors including Snail1, ZEB-1, and E-cadherin in cervical cancer (CC), precancerous and healthy samples, simultaneously, to find potential biomarkers. METHODS: The expression level of the mentioned cell factors were investigated in 72 CC patients, precancerous patients, and healthy controls by using Real-Time PCR. RESULTS: The results demonstrated a significant reduction in the expression level of E-cadherin in cancer and precancerous cases than that in healthy cases; whereas the expression level of ZEB-1 and Snail1 were upregulated in cancer and precancerous samples. The receiver operating characteristic (ROC) analyses shows the highest AUC value emerged for Snail1: 1(95% CI: 1-1) in comparing CC and healthy groups with a sensitivity of 100.0 % and specificity of 100.0%. CONCLUSION: The molecular biomarker Snail1 may be helpful to early diagnosis and prognosis of CC in the HPV-infected human populations. Considering the increased expression level of Snail1 in cancer and precancerous tissue compared to healthy tissue as well as the area under the ROC curve, Snail1 can be used for early detection of CC.

The dysregulation of microarray gene expression in cervical cancer is associated with overexpression of a unique messenger RNA signature.

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) is the fourth most common cause of cervical cancer (CC). The aim of the present study was to investigate gene expression levels of previously identified transcriptional signatures for malignant and non-malignant CC. MATERIALS AND METHODS: To validate of previously analyzed microarray gene expression data, we selected two hub genes (CDK1 and PLK1) and four differentially expressed mRNAs that were common in pre-malignant-normal and malignant-pre-malignant networks (SMS, NNT, UHMK1 and DEPDC1). To this purpose, the study included women diagnosed histologically with malignant CC (n=15), pre-malignant (n=15), and normal subjects (n=15). The expression of six host genes and viral E6/E7 genes were measured by quantitative Real-Time PCR. RESULTS: The results showed higher expression of CDK1/PLK1 hub genes and SMS, NNT and UHMK1 genes in malignant CC group than non-malignant CC group and normal group. A positive correlation was observed between gene expression of viral E6/E7 oncogenes and UHMK1 gene. CONCLUSION: Dysregulation of several mRNA signatures are a common feature of CC and can be potentially used as diagnostic and prognostic biomarkers as well as can be applied to therapeutic targets for CC treatment.

Identifying novel biomarkers of the pediatric influenza infection by weighted co-expression network analysis.

BACKGROUND: Despite the high yearly prevalence of Influenza, the pathogenesis mechanism and involved genes have not been fully known. Finding the patterns and mapping the complex interactions between different genes help us to find the possible biomarkers and treatment targets. METHODS: Herein, weighted gene co-expression network analysis (WGCNA) was employed to construct a co-expression network among genes identified by microarray analysis of the pediatric influenza-infected samples. RESULTS: Three of the 38 modules were found as the most related modules to influenza infection. At a functional level, we found that the genes in these modules regulate the immune responses, protein targeting, and defense to virus. Moreover, the analysis of differentially expressed genes disclosed 719 DEGs between the normal and infected subjects. The comprehensive investigation of genes in the module involved in immune system and viral defense (yellow module) revealed that SP110, HERC5, SAMD9L, RTP4, C19orf66, HELZ2, EPSTI1, and PHF11 which were also identified as DEGs (except C19orf66) have the potential to be as the biomarkers and also drug targeting for the treatment of pediatric influenza. CONCLUSIONS: The WGCN analysis revealed co-expressed genes which were involved in the innate immune system and defense to virus. The differentially expressed genes in the identified modules can be considered for designing drug targets. Moreover, modules can help to find pathogenesis routes in the future.

Serum and tissue miRNAs: potential biomarkers for the diagnosis of cervical cancer.

BACKGROUND: Finding new biomarkers for the early detection of cervical cancer is an essential requirement in this field. In this study, we aimed to evaluate the expression level of potential biomarkers in progression of cervical cancer in patients with cervical cancer compared to normal subjects. METHODS: The expression levels of tissue and serum miRNAs, including miR-9, miR-192 and miR-205, were investigated in 36 normal, 18 precancer, and 18 cervical cancer samples using real-time polymerase chain reaction. RESULTS: The results showed the higher significant expressions of miR-9, miR-192 and miR-205 in the tissue of cancer samples than those in the normal samples. Moreover, the miR-192 and miR-205 expression were significantly increased in the cancer group in comparison with the precancer group. Examination of serum samples revealed the increase in the expression level in the cancer groups than in the normal samples, for miR-9, miR-192 and miR-205 and the expressions of miR-9, miR-192 and miR-205 were significantly up-regulated in the precancer group in comparison with the normal group. Also the expression of miR-205 was remarkably increased in the cancer group in comparison with the precancer group. The receiver operating characteristic (ROC) analyses showed the highest area under the curve value for miR-192. CONCLUSIONS: Given the increased expression level of miR-192 in cancer and in precancerous tissue and serum compared with the normal tissue and serum validated by analysing the ROC curve, miR-192 can be used as potential biomarker for the early detection of cervical cancer.

Reconnaissance of the candidate genes involved in the pathogenesis of human immunodeficiency virus and targeted by antiretroviral therapy.

The expression levels of many genes change after treatment of human immunodeficiency virus (HIV)-infected subjects by antiretroviral drugs. High-throughput analysis of tremendous datasets led to the discovery of genes that are implicated in the treatment pathways. In this study, we performed a gene-enrichment analysis after determining the differentially expressed genes (DEGs) between untreated HIV-positive and HIV-negative subjects and also between treated HIV-positive subjects with antiretroviral therapy (ART; who receiving nucleoside reverse transcriptase inhibitor-based ART) and untreated HIV-positive cases in the peripheral blood mononuclear cells (PBMCs), adipose, and muscle tissues. In sum, the genes that activate inflammatory, immune response, proliferation, metabolism, and viral involvement pathways have different expression patterns in the untreated HIV-positive subjects and treated HIV-positive cases. Moreover, the expression levels of the genes including ACLY, ALDH18A1, HADHA, and YARS in the PBMCs tissue and HBEGF, PKN3, DEGS2, and EDN3 in the fat tissue were found to be different in the HIV-infected patients, which can be considered as new biomarkers for HIV infection.