scholarly journals The Catastrophic HPV/HIV Dual Viral Oncogenomics in Concert with Dysregulated Alternative Splicing in Cervical Cancer

2021 ◽  
Vol 22 (18) ◽  
pp. 10115
Author(s):  
Rahaba Marima ◽  
Rodney Hull ◽  
Georgios Lolas ◽  
Konstantinos N. Syrigos ◽  
Minah Kgoebane-Maseko ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Alternative Splicing ◽  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
Therapeutic Potential ◽  
Public Health Problem ◽  
Hiv Infections ◽  
Vital Role ◽  
African Women ◽  
Splicing Machinery

Cervical cancer is a public health problem and has devastating effects in low-to-middle-income countries (LTMICs) such as the sub-Saharan African (SSA) countries. Infection by the human papillomavirus (HPV) is the main cause of cervical cancer. HIV positive women have higher HPV prevalence and cervical cancer incidence than their HIV negative counterparts do. Concurrent HPV/HIV infection is catastrophic, particularly to African women due to the high prevalence of HIV infections. Although various studies show a relationship between HPV, HIV and cervical cancer, there is still a gap in the knowledge concerning the precise nature of this tripartite association. Firstly, most studies show the relationship between HPV and cervical cancer at genomic and epigenetic levels, while the transcriptomic landscape of this relationship remains to be elucidated. Even though many studies have shown HPV/HIV dual viral pathogenesis, the dual molecular oncoviral effects on the development of cervical cancer remains largely uncertain. Furthermore, the effect of highly active antiretroviral therapy (HAART) on the cellular splicing machinery is unclear. Emerging evidence indicates the vital role played by host splicing events in both HPV and HIV infection in the development and progression to cervical cancer. Therefore, decoding the transcriptome landscape of this tripartite relationship holds promising therapeutic potential. This review will focus on the link between cellular splicing machinery, HPV, HIV infection and the aberrant alternative splicing events that take place in HIV/HPV-associated cervical cancer. Finally, we will investigate how these aberrant splicing events can be targeted for the development of new therapeutic strategies against HPV/HIV-associated cervical cancer.

HIV Infection, AIDS and Vaccines

2021 ◽  
Author(s):  
Khrystyna Hrynkevych ◽  
Heinz-J. Schmitt
Keyword(s):  
Immune System ◽  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
Opportunistic Infections ◽  
Sexual Transmission ◽  
Hiv Infections ◽  
Perinatal Transmission ◽  
Human Immune System ◽  
Acute Hiv Infection ◽  
Acquired Immunodeficiency

HIV (human immunodeficiency virus) is a retrovirus that infects CD4+ T cells of the human immune system. If the infection is not treated, these cells are destroyed, resulting in an acquired immunodeficiency, i.e., “AIDS” (acquired immunodeficiency syndrome). HIV owns a reverse transcriptase enzyme to convert its RNA into DNA, which is then integrated into the human genome – then undetectable by the immune system. Today, sexual transmission is the major route of HIV infection, while parenteral transmission (sharing needles among drug addicts; rarely blood transfusion) and perinatal transmission are also possible. Acute HIV infection is accompanied by infectious mononucleosis-like symptoms (fevers, rash, lymphadenopathy, sore throat, fatigue), followed by a chronic asymptomatic stage, with viral replication at low levels, followed years later by AIDS, characterized by a plethora of possible opportunistic infections and cancers that result from T-cell deficiency and finally in death within about 2–3 years. Antiretroviral treatment (ART) includes 6 main classes of medicines that affect different steps of viral activities. While no cure is possible, ART – and particularly “Highly active antiretroviral therapy” (HAART) – has made HIV infections a chronic disease and therapy also results in a reduction of transmission. A large variety of vaccine candidates have been assessed – including phase 3 studies – but for many reasons, none of them have been successful to date.

Missed opportunity to diagnose HIV with Pneumocystis carinii pneumonia as its sequela

2020 ◽  
Vol 13 (6) ◽  
pp. e235386
Author(s):  
Louise Dunphy ◽  
Neil Patel ◽  
Bret Palmer ◽  
Edward McKeown
Keyword(s):  
Primary Care ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
Pneumocystis Carinii ◽  
Public Health Problem ◽  
Developed Countries ◽  
Solid Organ ◽  
Cd4 Cell Count ◽  
Highly Active

Pneumocystis carinii pneumonia (PCP) is an opportunistic infection of the lung occurring primarily in patients with HIV infection with a CD4 cell count <200 mm3, solid organ transplant recipients and those taking immunosuppressive therapy. The 1980s heralded the HIV pandemic, turning PCP into a major medical and public health problem worldwide. Manifestations of unusual infections such as pneumocystis and Kaposi’s sarcoma, were, after all, the first signs of the emerging pandemic to be recognised and may indeed, be the presenting feature of a previously undiagnosed HIV infection. With the advent of pneumocystis chemoprophylaxis and the initiation of highly active antiretroviral therapy, there has been a decreased incidence in developed countries, but it remains high in developing countries. Unfortunately, late presentation of HIV remains a problem resulting in significant morbidity and mortality. The authors report the case of a new diagnosis of HIV infection in a 45-year-old woman, presenting with a dry cough, dyspnoea, unintentional weight loss and PCP. Two weeks after commencing highly active antiretroviral therapy, she was diagnosed with immune reconstitution inflammatory syndrome. Research shows that stigma and discrimination in the healthcare setting contributes to keeping individuals from accessing HIV prevention, care and treatment services and adopting key preventive behaviours. The barriers to HIV testing and stigma eradication in primary care will be explored as well as missed opportunities to diagnosis HIV in primary care in individuals presenting with signs and symptoms of immunosuppression, in this case shingles.

An Overview of Antiretroviral Agents for Treating HIV Infection in Paediatric Population

2020 ◽  
Vol 27 (5) ◽  
pp. 760-794 ◽  
Author(s):  
Rita Melo ◽  
Agostinho Lemos ◽  
António J. Preto ◽  
Beatriz Bueschbell ◽  
Pedro Matos-Filipe ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Reverse Transcriptase ◽  
Targeted Delivery ◽  
Highly Active Antiretroviral Therapy ◽  
Antiretroviral Drugs ◽  
Viral Reservoir ◽  
Reverse Transcriptase Inhibitors ◽  
Replication Process ◽  
Antiretroviral Agents ◽  
Multiple Drugs

Paediatric Acquired ImmunoDeficiency Syndrome (AIDS) is a life-threatening and infectious disease in which the Human Immunodeficiency Virus (HIV) is mainly transmitted through Mother-To- Child Transmission (MTCT) during pregnancy, labour and delivery, or breastfeeding. This review provides an overview of the distinct therapeutic alternatives to abolish the systemic viral replication in paediatric HIV-1 infection. Numerous classes of antiretroviral agents have emerged as therapeutic tools for downregulation of different steps in the HIV replication process. These classes encompass Non- Nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs), Nucleoside/Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs/NtRTIs), INtegrase Inhibitors (INIs), Protease Inhibitors (PIs), and Entry Inhibitors (EIs). Co-administration of certain antiretroviral drugs with Pharmacokinetic Enhancers (PEs) may boost the effectiveness of the primary therapeutic agent. The combination of multiple antiretroviral drug regimens (Highly Active AntiRetroviral Therapy - HAART) is currently the standard therapeutic approach for HIV infection. So far, the use of HAART offers the best opportunity for prolonged and maximal viral suppression, and preservation of the immune system upon HIV infection. Still, the frequent administration of high doses of multiple drugs, their inefficient ability to reach the viral reservoirs in adequate doses, the development of drug resistance, and the lack of patient compliance compromise the complete HIV elimination. The development of nanotechnology-based drug delivery systems may enable targeted delivery of antiretroviral agents to inaccessible viral reservoir sites at therapeutic concentrations. In addition, the application of Computer-Aided Drug Design (CADD) approaches has provided valuable tools for the development of anti-HIV drug candidates with favourable pharmacodynamics and pharmacokinetic properties.

Medicinal Plants and Bioactive Compounds for Diabetes Management: Important Advances for Drug Discovery

2020 ◽  
Vol 26 ◽  
Author(s):  
Kondeti Ramudu Shanmugam ◽  
Bhasha Shanmugam ◽  
Gangigunta Venkatasubbaiah ◽  
Sahukari Ravi ◽  
Kesireddy Sathyavelu Reddy
Keyword(s):  
Herbal Medicine ◽  
Medicinal Plants ◽  
Bioactive Compounds ◽  
Diabetes Management ◽  
Therapeutic Potential ◽  
Public Health Problem ◽  
In Vivo Studies ◽  
Major Public Health Problem

Background : Diabetes is a major public health problem in the world. It affects each and every part of the human body and also leads to organ failure. Hence, great progress made in the field of herbal medicine and diabetic research. Objectives: Our review will focus on the effect of bioactive compounds of medicinal plants which are used to treat diabetes in India and other countries. Methods: Information regarding diabetes, oxidative stress, medicinal plants and bioactive compounds were collected from different search engines like Science direct, Springer, Wiley online library, Taylor and francis, Bentham Science, Pubmed and Google scholar. Data was analyzed and summarized in the review. Results and Conclusion: Anti-diabetic drugs that are in use have many side effects on vital organs like heart, liver, kidney and brain. There is an urgent need for alternative medicine to treat diabetes and their disorders. In India and other countries herbal medicine was used to treat diabetes. Many herbal plants have antidiabetic effects. The plants like ginger, phyllanthus, curcumin, aswagandha, aloe, hibiscus and curcuma showed significant anti-hyperglycemic activities in experimental models and humans. The bioactive compounds like Allicin, azadirachtin, cajanin, curcumin, querceitin, gingerol possesses anti-diabetic, antioxidant and other pharmacological properties. This review focuses on the role of bioactive compounds of medicinal plants in prevention and management of diabetes. Conclusion: Moreover, our review suggests that bioactive compounds have the potential therapeutic potential against diabetes. However, further in vitro and in vivo studies are needed to validate these findings.

scholarly journals PPM1G promotes the progression of hepatocellular carcinoma via phosphorylation regulation of alternative splicing protein SRSF3

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Dawei Chen ◽  
Zhenguo Zhao ◽  
Lu Chen ◽  
Qinghua Li ◽  
Jixue Zou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Alternative Splicing ◽  
Protein Function ◽  
Vital Role ◽  
Normal Tissues ◽  
Mechanistic Analysis ◽  
Highly Correlated ◽  
Splicing Patterns

AbstractEmerging evidence has demonstrated that alternative splicing has a vital role in regulating protein function, but how alternative splicing factors can be regulated remains unclear. We showed that the PPM1G, a protein phosphatase, regulated the phosphorylation of SRSF3 in hepatocellular carcinoma (HCC) and contributed to the proliferation, invasion, and metastasis of HCC. PPM1G was highly expressed in HCC tissues compared to adjacent normal tissues, and higher levels of PPM1G were observed in adverse staged HCCs. The higher levels of PPM1G were highly correlated with poor prognosis, which was further validated in the TCGA cohort. The knockdown of PPM1G inhibited the cell growth and invasion of HCC cell lines. Further studies showed that the knockdown of PPM1G inhibited tumor growth in vivo. The mechanistic analysis showed that the PPM1G interacted with proteins related to alternative splicing, including SRSF3. Overexpression of PPM1G promoted the dephosphorylation of SRSF3 and changed the alternative splicing patterns of genes related to the cell cycle, the transcriptional regulation in HCC cells. In addition, we also demonstrated that the promoter of PPM1G was activated by multiple transcription factors and co-activators, including MYC/MAX and EP300, MED1, and ELF1. Our study highlighted the essential role of PPM1G in HCC and shed new light on unveiling the regulation of alternative splicing in malignant transformation.

scholarly journals Hematological Profile of HIV-Infected Patients on First-Line Highly Active Antiretroviral Therapy and Its Correlation With CD4 Count

2021 ◽  
Author(s):  
John Jospeh Diamond Princy ◽  
Kshetrimayum Birendra Singh ◽  
Ningthoujam Biplab ◽  
Ningthoukhongjam Reema ◽  
Rajesh Boini ◽  
...  
Keyword(s):  
Platelet Count ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
Cd4 Count ◽  
Total Leukocyte Count ◽  
Hiv Patients ◽  
Positive Correlation ◽  
Highly Active ◽  
The Mean

Abstract Introduction Human immunodeficiency virus (HIV) infection is a state of profound immunodeficiency. Disorders of hematopoietic system are a common but often overlooked complication of HIV infection. This can manifest at any stage of the disease but more commonly in the advanced stage with low CD4 count. Anemia is the most common hematological abnormality in HIV patients and prevalence ranges from 1.3 to 95%. As HIV disease progresses, the prevalence and severity of anemia also increase. Hence, this study was undertaken to assess the hematological parameters of HIV-infected patients on highly active antiretroviral therapy (HAART) at different treatment durations with the hope to improve the HAART outcome in HIV patients and its correlation with CD4 count. Methods This prospective longitudinal study enrolled 134 HIV-infected patients admitted to or attending the OPD in the Department of Medicine or Antiretroviral Therapy (ART) Center (Center of Excellence), Regional Institute of Medical Sciences (RIMS), Imphal, Manipur, from 2018 to 2020. Complete hemogram, CD4 count, and other related-blood investigations were studied. Results The mean age of the study population was 39.9 ± 11.04 years. Of the 134 patients, 75 (56%) were males and 59 (44%) were females. Twelve (9%) patients had a history of injecting drug use (IDU). TLE (tenofovir, lamivudine, efavirenz) regimen was started on 112 (83.6%) patients and the majority of them (69/134 [51.5%]) had a CD4 count of 200 to 499 cells/mm3, which increased significantly 6 months after HAART to 99 to 1,149 cells/mm3, with a mean of 445 ± 217 cells/mm3. There were significant improvements in hemoglobin (Hb) levels, total leukocyte count (TLC), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) after HAART indicating a positive correlation with CD4 count (p < 0.05). Thrombocytopenia was observed higher after HAART when compared to baseline. There was a positive correlation between platelet count and CD4 count. However, the mean corpuscular volume (MCV) and erythrocyte sedimentation rate (ESR) had a negative correlation with CD4 count. Conclusion The study inferred a strong positive correlation between CD4 and Hb levels, TLC, ANC, ALC, and platelet count after HAART with improvement in these values as CD4 count increases. Specific treatment intervention based on the changes in the immunohematological profile trends can help prevent most of the adverse effects on HIV patients in our community.

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