Risk Factors Associated with Opportunistic Infections among People Living with HIV/AIDS and Receiving an Antiretroviral Therapy in Gabon, Central Africa.

The Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is still one of the main causes of death in sub-Saharan Africa. Antiretroviral therapies (ARTs) have significantly improved the health conditions of people living with HIV/AIDS (PLWHA). Consequently, a significant drop in morbidity and mortality, along with a reduced incidence of opportunistic infections (OIs), has been observed. However, certain atypical and biological profiles emerge in ART patients post-examination. The objective of this study was to identify the risk factors that contributed to the onset of OIs in HIV patients undergoing ART in Gabon. Epidemiological and biological data were obtained from medical records (2017 to 2019) found at the outpatient treatment centre (CTA) of Franceville in Gabon. Samples for blood count, CD4, and viral load analysis at CIRMF were collected from PLWHA suffering from other pathogen-induced conditions. A survey was carried out and data were analysed using Rstudio 4.0.2 and Excel 2007 software. Biological and socio-demographic characteristics were examined concerning OIs through both a univariate analysis via Fisher's exact tests or chi2 (χ2), and a multivariate analysis via logistic regression. Out of the 300 participants initially selected, 223 were included in the study, including 154 (69.05%) women and 69 (30.95%) men. The mean age was 40 (38.6; 41.85), with individuals ranging from 2 to 77 years old. The study cohort was classified into five age groups (2 to 12, 20 to 29, 30 to 39, 40 to 49, and 50 to 77 years old), among which the groups aged 30 to 39 and 40 to 49 emerged as the largest, comprising 68 (30.5%) and 75 (33.6%) participants, respectively. It was noted that 57.9% of PLWHA had developed OIs and three subgroups were distinguished, with parasitic, viral, and bacterial infections present in 18%, 39.7%, and 55.4% of cases, respectively. There was a correlation between being male and having a low CD4 T-cell count and the onset of OIs. The study revealed a high overall prevalence of OIs, and extending the study to other regions of Gabon would yield a better understanding of the risk factors associated with the onset of these infections.

Human T-Cell Leukemia Virus Type 1-Related Diseases May Constitute a Threat to the Elimination of Human Immunodeficiency Virus, by 2030, in Gabon, Central Africa.

The Joint United Nations Program on HIV/AIDS (UNAIDS) has adopted the Sustainable Development Goals (SDGs) to end the HIV/AIDS epidemic by 2030. Several factors related to the non-suppression of HIV, including interruptions of antiretroviral therapy (ART) and opportunistic infections could affect and delay this projected epidemic goal. Human T-Cell leukemia virus type 1 (HTLV-1) appears to be consistently associated with a high risk of opportunistic infections, an early onset of HTLV-1 and its associated pathologies, as well as a fast progression to the AIDS phase in co-infected individuals, when compared to HIV-1 or HTLV-1 mono-infected individuals. In Gabon, the prevalence of these two retroviruses is very high and little is known about HTLV-1 and the associated pathologies, leaving most of them underdiagnosed. Hence, HTLV-1/HIV-1 co-infections could simultaneously imply a non-diagnosis of HIV-1 positive individuals having developed pathologies associated with HTLV-1, but also a high mortality rate among the co-infected individuals. All of these constitute potential obstacles to pursue targeted objectives. A systematic review was conducted to assess the negative impacts of HTLV-1/HIV-1 co-infections and related factors on the elimination of HIV/AIDS by 2030 in Gabon.

Photodynamic Therapy: A Prospective Therapeutic Approach for Viral Infections and Induced Neoplasia.

The recent COVID-19 pandemic outbreak and arising complications during treatments have highlighted and demonstrated again the evolving ability of microorganisms, especially viral resistance to treatment as they develop into new and strong strains. The search for novel and effective treatments to counter the effects of ever-changing viruses is undergoing. Although it is an approved procedure for treating cancer, photodynamic therapy (PDT) was first used against bacteria and has now shown potential against viruses and certain induced diseases. PDT is a multi-stage process and uses photosensitizing molecules (PSs) that accumulate in diseased tissues and eradicates them after being light-activated in the presence of oxygen. In this review, studies describing viruses and their roles in disrupting cell regulation mechanisms and signaling pathways and facilitating tumorigenesis were described. With the development of innovative "or smart" PSs through the use of nanoparticles and two-photon excitation, among other strategies, PDT can boost immune responses, inactivate viral infections, and eradicate neoplastic cells. Visualization and monitoring of biological processes can be achieved in real-time with nanomedicines and better tissue penetration strategies. After photodynamic inactivation of viruses, signaling pathways seem to be restored but the underlying mechanisms are still to be elucidated. Light-mediated treatments are suitable to manage both oncogenic viral infections and induced neoplasia.

Features of third generation photosensitizers used in anticancer photodynamic therapy: Review.

Cancer remains a main public health issue and the second cause of mortality worldwide. Photodynamic therapy is a clinically approved therapeutic option. Effective photodynamic therapy induces cancer damage and death through a multifactorial manner including reactive oxygen species-mediated damage and killing, vasculature damage, and immune defense activation. Anticancer efficiency depends on the improvement of photosensitizers drugs used in photodynamic therapy, their selectivity, enhanced photoproduction of reactive species, absorption at near-infrared spectrum, and drug-delivery strategies. Both experimental and clinical studies using first- and second-generation photosensitizers had pointed out the need for developing improved photosensitizers for photodynamic applications and achieving better therapeutic outcomes. Bioconjugation and encapsulation with targeting moieties appear as a main strategies for the development of photosensitizers from their precursors. Factors influencing cellular biodistribution and uptake are briefly discussed, as well as their roles as cancer diagnostic and therapeutic (theranostics) agents. The two-photon photodynamic approach using third-generation photosensitizers is present as an attempt in treating deeper tumors. Although significant advances had been made over the last decade, the development of next-generation photosensitizers is still mainly in the developmental stage.

Learning from Nature: Bioinspired Chlorin-Based Photosensitizers Immobilized on Carbon Materials for Combined Photodynamic and Photothermal Therapy.

Chlorophylls, which are chlorin-type photosensitizers, are known as the key building blocks of nature and are fundamental for solar energy metabolism during the photosynthesis process. In this regard, the utilization of bioinspired chlorin analogs as photosensitizers for photodynamic therapy constitutes an evolutionary topic of research. Moreover, carbon nanomaterials have been widely applied in photodynamic therapy protocols due to their optical characteristics, good biocompatibility, and tunable systematic toxicity. Herein, we review the literature related to the applications of chlorin-based photosensitizers that were functionalized onto carbon nanomaterials for photodynamic and photothermal therapies against cancer. Rather than a comprehensive review, we intended to highlight the most important and illustrative examples over the last 10 years.

Nano-Mediated Photodynamic Therapy for Cancer: Enhancement of Cancer Specificity and Therapeutic Effects.

Deregulation of cell growth and development lead to cancer, a severe condition that claims millions of lives worldwide. Targeted or selective approaches used during cancer treatment determine the efficacy and outcome of the therapy. In order to enhance specificity and targeting and obtain better treatment options for cancer, novel modalities are currently under development. Photodynamic therapy has the potential to eradicate cancer, and combination therapy would yield even greater outcomes. Nanomedicine-aided cancer therapy shows enhanced specificity for cancer cells and minimal side-effects coupled with effective cancer destruction both in vitro and in vivo. Nanocarriers used in drug-delivery systems are very capable of penetrating the cancer stem cell niche, simultaneously killing cancer cells and eradicating drug-resistant cancer stem cells, yielding therapeutic efficiency of up to 100-fold against drug-resistant cancer in comparison with free drugs. Safety precautions should be considered when using nano-mediated therapy as the effects of extended exposure to biological environments are still to be determined.

Evaluation of cell damage induced by irradiated Zinc-Phthalocyanine-gold dendrimeric nanoparticles in a breast cancer cell line.

BACKGROUND: Cancer is a non-communicable disease that occurs following a mutation in the genes which control cell growth. Breast cancer is the most diagnosed cancer among South African women and a major cause of cancer-related deaths worldwide. Photodynamic therapy (PDT) is an alternative cancer therapy that uses photochemotherapeutic agents, known as photosensitizers. Drug-delivery nanoparticles are commonly used in nanomedicine to enhance drug-therapeutic efficiency. This study evaluated the photodynamic effects following treatment with 0.3 µM multiple particles delivery complex (MPDC) and irradiated with a laser fluence of 10 J/cm2 using a 680 nm diode laser in a breast cancer cell line (MCF-7). METHODS: Cell damage was assessed by inverted light microscopy for cell morphology; the Apoptox-Glo triple assay was used for cell viability, caspase activity and identification of cytodamage markers; flow cytometric analysis for cell death pathways and mitochondrial membrane potential; the enzyme linked immunosorbent assay (ELISA) for cytochrome C release; and real-time reverse transcriptase polymerase chain reaction (RT-PCR) array for gene expression. RESULTS: Laser activated-MPDC induced a significant change in morphology of PDT-treated cells, with the appearance of apoptotic like morphological features. An increase in cytotoxicity, caspase activity, cell depolarization and cytochrome C release were identified in PDT-treated cells. Finally, the upregulation of BAX, BCL-2, CASP-2 and ULK-1 genes was observed. CONCLUSION: The MPDC yielded a successful and stable hybrid agent with potent photodynamic abilities.

Characterization of a multiple particle delivery complex and determination of cellular photodamage in skin fibroblast and breast cancer cell lines.

Zinc metallized Phthalocyanine (ZnPcSmix ), a potent photosensitizer, is conjugated to gold dendrimer encapsulated nanoparticles (AuDENPs) in order to improve the efficacy of photodynamic therapy (PDT) using MCF-7 breast cancer cells and WS1 fibroblast cells as a control. Both ZnPcSmix and AuDENPs are mixed in a nitrogen atmosphere for 48 hours and characterization analysis conducted using ultraviolet-visible (UV-vis) spectrometry for spectral properties, transmission electron microscopy (TEM) for morphological features and zeta potential measurement for surface stability and size distribution of the compound obtained or of the multiple particles delivery complex (MPDC). Cell viability, proliferation and membrane damage following PDT are assessed by the trypan blue exclusion test, adenosine triphosphate luminescence and lactate dehydrogenase cytotoxicity assays, respectively. Stable MPDCs are spherical shaped with a diameter lesser than 5 nm, and have a maximum absorption peak at 676 nm. The MPDC-mediated PDT induces a decrease in cell viability and proliferation, and increased membrane damage or cytotoxicity. The conjugation enhances the therapeutic efficiency of PDT by improving drug delivery and targeting of MCF-7 cancer cells.

Comparative study between the photodynamic ability of gold and silver nanoparticles in mediating cell death in breast and lung cancer cell lines.

Cancer is one of the dreadest diseases once diagnosed and has severe impacts on health, social and economic global aspects. Nanomedicine is considered an emerging approach for early cancer diagnosis and treatment. The multifunctional effects of silver and gold nanoparticles (Ag and Au NPs) have rendered them to be potent candidates for biomedical applications. The current work presents a comparative study between Au NPs and Ag NPs as possible potent photosensitizers (PS) in photodynamic therapy (PDT). Transmission electron microscopy (TEM) was used to identify and characterize the shape, size, and cellular localization of Au NPs; the absorption properties of Au NPs were determined using ultraviolet-visible spectroscopy (UV-Vis) and zeta potential was used to identify surface charge. Inverted light microscopy (LM), Trypan blue exclusion assay, adenosine triphosphate luminescence (ATP), and lactate dehydrogenase membrane integrity assays (LDH) were used for investigating the photodynamic ability of these nanostructures on breast (MCF-7) and lung (A549) cancer cell lines. Flow cytometry using Annexin V and propidium iodide (PI) dyes was used to determine the cell death pathway induced. The average size of the synthesized Au NPs was 50 nm, having an absorption peak at 540 nm with -7.85 mV surface net charge. MCF-7 and A549 cells were able to absorb the Au NPs. The latter, when irradiated with laser light in the phototherapeutic window, promoted cytotoxicity and a significant reduction in cell viability and proliferation were observed. The photodynamic activity that was observed in both cancer cell lines was found to be less eminent than that observed in case of the Ag NPs when compared to Au NPs. The present study is the first that compares the photodynamic ability of two different nanoparticles, silver and gold, as photosensitizers without any further functionalization. This study extends the possibilities of using such nanostructures in PDT within the therapeutic window wavelength, yet through the conjugation of Au NPs with other photosensitizers to synergize its effect.

Cell death pathways and phthalocyanine as an efficient agent for photodynamic cancer therapy.

The mechanisms of cell death can be predetermined (programmed) or not and categorized into apoptotic, autophagic and necrotic pathways. The process of Hayflick limits completes the execution of death-related mechanisms. Reactive oxygen species (ROS) are associated with oxidative stress and subsequent cytodamage by oxidizing and degrading cell components. ROS are also involved in immune responses, where they stabilize and activate both hypoxia-inducible factors and phagocytic effectors. ROS production and presence enhance cytodamage and photodynamic-induced cell death. Photodynamic cancer therapy (PDT) uses non-toxic chemotherapeutic agents, photosensitizer (PS), to initiate a light-dependent and ROS-related cell death. Phthalocyanines (PCs) are third generation and stable PSs with improved photochemical abilities. They are effective inducers of cell death in various neoplastic models. The metallated PCs localize in critical cellular organelles and are better inducers of cell death than other previous generation PSs as they favor mainly apoptotic cell death events.

Induced cell death pathway post photodynamic therapy using a metallophthalocyanine photosensitizer in breast cancer cells.

OBJECTIVE: Zinc phthalocyanine (ZnPcSmix) was used as the photosensitizer (PS) in this study to investigate the cell death patterns as a result of photodynamic therapy (PDT) in a breast cancer cell line (MCF-7) in vitro using a 680 nm diode laser at a fluence of 5 J/cm(2). BACKGROUND: PDT is a noninvasive form of cancer therapy, successfully applied for the treatment of various cancer types. METHODS: Flow cytometry using Annexin V-fluorescein isothiocyanate (FITC), a cell death immunosorbent assay (ELISA), and gene expression analysis following ZnPcSmix mediated PDT were performed to determine the induced cell death pathways. RESULTS: The apoptotic cells abounded after the treatment, nuclear fragmentation was seen as oligonucleosomal degradation and increased expression of the B-cell lymphoma 2 (Bcl-2), DNA fragmentation factor alpha (DFFA1), and caspase 2 (CASP2) genes, indicated that apoptosis is the main induced mode of cell death. CONCLUSIONS: ZnPcSmix mediated PDT led to an apoptotic cell death pathway and the PS used showed its ability to stimulate and initiate programmed cell death.