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10 result(s) for "Ndayambaje, Martin"
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Therapeutic Management of Ebola Virus: Targeting Oxidative Stress and Inflammatory Pathways
The Ebola virus (EBOV), a highly lethal pathogen causing hemorrhagic fever, poses a persistent public health threat, with devastating multi-organ complications and high transmission potential through bodily fluids. EBOV’s pathogenesis is marked by severe oxidative stress and immune dysregulation, where increased reactive oxygen species (ROS) levels foster cellular damage, hinder immune defenses, and facilitate viral replication. Through immune evasion and suppression of cellular stress responses, EBOV affects both innate and adaptive immunity, activating pyroptosis, PANoptosis, necroptosis, and lymphocyte apoptosis, thereby amplifying inflammation and disease severity. Recent research suggests that bioactive molecules, including quercetin, curcumin, eugenol, and p-anisaldehyde, may offer therapeutic potential due to their antioxidant, anti-inflammatory, and immunomodulatory effects. This review also underscores the potential of conventional treatments, including amiodarone, favipiravir, remdesivir, azithromycin, chloroquine, and nitazoxanide, as therapeutic agents against EBOV, thanks to their antiviral and anti-inflammatory properties, although their efficacy varies across experimental models. These natural compounds could enhance immune resilience by scavenging ROS, modulating inflammation, and mitigating immune dysregulation, presenting promising adjunctive strategies to support conventional EBOV therapies.
Plant-derived molecules in monkeypox management: insight and alternative therapeutic strategies
The WHO and CDC recently declared monkeypox virus (MPXV) a zoonotic disease known as monkeypox (Mpox) a Public Health Emergency of International Concern. According to the CDC, no treatment is specifically approved for Mpox infections. Medicinal plants are crucial in healthcare and economic development, particularly for low- and middle-income countries. This review offers valuable insights into the pathogenesis and the management of Mpox through therapeutic approaches and vaccination strategies using plant-based molecules. Core structural proteins necessary for both viral entry and the immune response, including A29, H3L, and L1R, are involved in the pathogenesis of MPXV. Potential targets for vaccines include proteins like A35R and B6R, which are essential to the propagation of viruses. The MPXV evades the immune system by concealing its DNA, suppressing the interferon response, limiting T and NK cell activation, and preventing apoptosis, complicating vaccine and treatment development. Antivirals (tecovirimat, brincidofovir) and vaccinations (JYNNEOS, ACAM2000) manage Mpox. A recent study revealed early clinical trial results, indicating that the antiviral drug tecovirimat, a well-known conventional treatment, is no more effective than a placebo against the clade I virus type Research gaps, low vaccination effectiveness, and availability are challenges. This review offers a novel perspective on combating the global threat of Mpox by investigating alternative management strategies centered on plant-derived compounds. Graphical Abstract
Molecular characterization of Ebola virus, immune response, and therapeutic challenges: a narrative review
The Ebola virus (EBOV) remains a major public health challenge due to its complex structure and the lack of appropriate and effective vaccines and therapies. This review characterizes the Ebola virus, its immune response, and its therapeutic challenges. Structural EBOV proteins include the envelope glycoprotein, nucleoprotein, RNA polymerase L, and viral proteins VP30, VP24, VP35, and VP40. The proteins play a role in the virus's pathogenesis by evading the host's immune response. The immune system evasion mechanisms of EBOV are critical in its pathogenesis. Some vaccines, such as the recombinant vesicular stomatitis virus-Zaire Ebola virus (RVSV-ZEBOV), have proven to be very effective and have been approved by the Food and Drug Administration (FDA) additionally, four other vaccines have been approved including Gam Evac-Combi (licensed in Russia), ad5-EBOV (approved in China), Zabdeno and Mvabea (approved in Europe). However, some challenges remain in developing effective vaccines, such as the selection of immunogens, cross-protecting immunity, long-term protection, mechanism of protection, and rapid response vaccination. Despite the progress made, there is still a need for an effective vaccine that offers durable and broad protection against multiple strains of the Ebola virus. This will be achieved through the collaboration of various organizations and government and Non-Governmental Organization (NGO) agencies.
Artemisia herba-alba: antioxidant capacity and efficacy in preventing chronic arthritis in vivo
Arthritis is a debilitating condition impacting the quality of life for millions worldwide, characterized by pain and inflammation. Understanding the mechanisms of arthritis and developing effective treatments are crucial. This study investigated the hydroethanolic extract of Artemisia herba-alba for its protective potential against arthritis hallmarks, oxidative stress, and lipid peroxidation in vitro. It also assessed its in vivo anti-arthritic activity. The phytochemical analysis identified various compounds within the extract, with high concentrations of polyphenols and flavonoids. These compounds are associated with numerous health benefits, making A. herba-alba a potential source of valuable phytochemicals. A. herba-alba demonstrated a notable effect in body weight loss, paw edema, and arthritic severity. Histopathological examination revealed structural improvements in bone and muscle tissues, emphasizing its therapeutic potential in managing chronic arthritis. Furthermore, while these findings are promising, further studies are necessary to delve deeper into the mechanisms underlying the observed hematological changes and to gain a more comprehensive understanding of the in vivo results. This research sets the stage for continued exploration, ultimately aiming to unlock the full potential of A. herba-alba in addressing chronic arthritis and enhancing the lives of those affected by this condition.
Phytochemical Characteristics, Antioxidant, and Antimicrobial Activities and In Silico Prediction of Bioactive Compounds from Cedrus atlantica Wood Tar
Cedrus atlantica wood tar (CAWT) is traditionally used as a medicinal product, especially in low- and middle-income countries. Despite its traditional use, scientific support for its efficacy remains limited. This study evaluated the biological properties of CAWT using an integrated approach that combined qualitative and quantitative phytochemical analysis, disc diffusion and microdilution tests for antimicrobial assays (disc diffusion and microdilution), antioxidant activity (DPPH and ferric-reducing power assays), in silico ADMET/toxicity, docking, and MD/MMGBSA and provided a balanced comparison with reference antioxidants. This study demonstrated that CAWT is rich in secondary metabolites linked to biological activity, including polyphenols (307.39 ± 58.45 mg GAE/g), tannins (124.42 ± 6.14 mg TAE/g), and flavonoids (15.62 ± 2.53 mg QE/g). For free radical scavenging, CAWT inhibited DPPH with an IC50 of 19.781 ± 2.51 µg/mL and showed ferric-reducing activity with an IC50 of 83.7 ± 2.88 µg/mL for its antimicrobial activity against Pseudomonas aeruginosa; inhibition zones reached 35.66 ± 0.58 mm. In silico analysis, Swiss ADMET and pkCSM predicted ≥94% intestinal absorption, no cytochrome P450 liabilities, and low acute toxicity for six dominant terpenoids. Docking pinpointed trans-cadina-1(6),4-diene and α/β-himachalene as high-affinity ligands of LasR and gyrase B (ΔG ≈ −8 kcal mol−1). A 100 ns GROMACS run confirmed stable hydrophobic locking of the lead LasR complex (RMSD 0.22 nm), while MM/GBSA calculated a dispersion-dominated binding free energy of −37 kcal mol−1. Overall, CAWT showed in vitro antioxidant activity (DPPH and ferric-reducing assays) and inhibitory effects in disc diffusion assays, while in silico predictions for major terpenoids suggested favorable oral absorption and low acute toxicity. However, chemical composition analysis and bio-guided fractionation are necessary to confirm the antimicrobial activity and to validate the compounds responsible for the observed effects.
Vernonia amygdalina Delile and cancer: a comprehensive review of its chemopreventive mechanisms and efficacy
Cancer, distinguished by the uncontrolled proliferation and spread of malignantly altered cells, poses a substantial worldwide health concern. The complex series of events in cancer progression entails intricate molecular and genetic changes occurring within specific cellular targets. Cancer chemoprevention has emerged as a crucial approach to alleviate the burden of cancer on healthcare systems. This strategy involves the utilization of pharmacologically natural molecules and active substances to impede, suppress, forestall, or reverse the progression of invasive cancer. Among these substances, Vernonia amygdalina Delile (VAD ) demonstrated therapeutic properties. This review elicits the detailed potential of VAD in combating multiple cancers by targeting cancer pathways. VAD has demonstrated noteworthy preventive capabilities by inhibiting cellular growth, migration, and invasion of cancer cells, stimulating cell death, and regulating signaling routes associated with cancer initiation. Furthermore, the VAD 's leaf extract has been identified to contain bioactive molecules that contribute to its cytotoxic, antioxidant, and anticancer activities. Despite progress in the exploration of VAD 's chemopreventive attributes, there are shortcomings in both in vivo studies and individual molecular scrutiny. Future research efforts should emphasize in vivo experimentation and clinical trials while carefully delineating the signaling pathways involved.
Stathmin-2 loss leads to neurofilament-dependent axonal collapse driving motor and sensory denervation
The mRNA transcript of the human STMN2 gene, encoding for stathmin-2 protein (also called SCG10), is profoundly impacted by TAR DNA-binding protein 43 (TDP-43) loss of function. The latter is a hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Using a combination of approaches, including transient antisense oligonucleotide-mediated suppression, sustained shRNA-induced depletion in aging mice, and germline deletion, we show that stathmin-2 has an important role in the establishment and maintenance of neurofilament-dependent axoplasmic organization that is critical for preserving the caliber and conduction velocity of myelinated large-diameter axons. Persistent stathmin-2 loss in adult mice results in pathologies found in ALS, including reduced interneurofilament spacing, axonal caliber collapse that drives tearing within outer myelin layers, diminished conduction velocity, progressive motor and sensory deficits, and muscle denervation. These findings reinforce restoration of stathmin-2 as an attractive therapeutic approach for ALS and other TDP-43-dependent neurodegenerative diseases. Stathmin-2 is lost in amyotrophic lateral sclerosis. Here the authors show that stathmin-2 has an essential role in the maintenance of axon structure, with its loss from adult motor neurons resulting in axonal collapse and muscle denervation.
Pesticide Application Practices and Knowledge among Small-Scale Local Rice Growers and Communities in Rwanda: A Cross-Sectional Study
Background: Agriculture contributes a third of Rwanda’s GDP and is the main source of income for rural households, with 80% of the total population involved in crop and/or livestock production. The Government of Rwanda established the Muvumba rice project in 2011 amidst a policy shift towards rice as a national staple crop. However, the indiscriminate use of pesticides by local, low-income rice growers has raised concerns about potential human, animal and ecosystem health impacts as pesticide distribution and application are not strictly regulated. Although pesticide use can directly influence farmer health and ecosystems, little is known about small-scale farmers’ pesticide application practices and knowledge. We aimed to assess local application practices and understanding of pesticides to identify gaps in farmers’ knowledge on safe pesticide use and deviations from established standards and recommended practices. Methods: We conducted a cross-sectional study consisting of observations of pesticide practices and interviews with 206 small-scale rice growers in Nyagatare District, Rwanda, in March 2017. Descriptive statistical analyses (sample means, standard deviation and range) were performed, and we evaluated the association between farmers’ personal protective equipment (PPE) use and their education level and literacy status. Results: Over 95% of observed farmers did not comply with minimum standards for safe pesticide use, and 80% of respondents reported that they stored pesticides in their homes without personal protection measures. Education and literacy level were not significantly associated with PPE use. Additionally, 90% of respondents had experienced adverse health effects after using pesticides including intense headache, dizziness, stomach cramps, skin pain and itching, and respiratory distress. All respondents also reported animals in and around the rice scheme (cattle, birds, and fish) behaving abnormally or with signs consistent with pesticide exposure in the six months preceding the study, which may be linked to pesticide-contaminated water. Conclusions: Our study demonstrates potential for high exposure to pesticides for farmers, their families, and animals sharing rice-growing or downstream environments and points to the need for training on safe and effective pesticide use.
Microbial identification of potato taste defect from coffee beans
Coffee is a socioeconomic important plant all over the world due to its exportation and how it provides income to the farmers and the country. However, potato taste defect (PTD) affects the Rwandan coffee quality. The smell is reported to be caused by some bacteria that are responsible for the off‐flavor and may also be related to the infestation of Antestia pest which are in its elimination process. The aim of this study was to isolate, biochemically characterize, and identify bacteria producing potato flavor from Rwandan coffee. Five samples were obtained from different regions (Nyamasheke and Nyakizu) of Rwanda. Bacteria were isolated and enumerated in the nutrient agar media followed by culture on nutrient and tryptic soy broth media. Bacteria were also cultured to several carbon sources such as glucose, fructose, sucrose, starch, pectin, and galactose to smell the odor produced by those bacteria. DNA extraction of isolates was done, and the resulting DNA strands were undergone three steps of PCR to be amplified using the forward primer and reverse primer. The identification of bacteria producing potato flavor from Rwandan coffee beans was done through 16S rDNA method followed by sequence analysis using FinchTV software and BLAST. Earthy odor was the mostly produced one for nutrient agar and tryptic soy agar media, and for carbon sources such as sucrose, glucose, pectin, fructose, and galactose. The potato odor was recorded mostly from damaged floaters and hand‐sorted damaged coffee beans. However, other odors such as fruity and ferment were found to be produced by bacteria in coffee beans. The study came up by concluding the presence of different kinds of bacteria including Enterobacteriaceae and Pantoea, which are responsible for the formation of 2‐isopropyl‐3‐methoxypyrazine (IMP) in coffee beans and cause the production of potato flavor. Potato taste defect (PTD) affects coffee quality, and the presence of bacteria including Enterobacteriaceae and Pantoea could be responsible for the formation of 2‐isopropyl‐3‐methoxypyrazine (IMP) in coffee beans and cause the production of potato flavor.
Stathmin-2 loss leads to neurofilament-dependent axonal collapse driving motor and sensory denervation
The human mRNA most affected by TDP-43 loss-of-function is transcribed from the STMN2 gene and encodes stathmin-2 (also known as SCG10), whose loss is a neurodegenerative disease hallmark. Here using multiple in vivo approaches, including transient antisense oligonucleotide (ASO)-mediated suppression, chronic shRNA-mediated depletion in aging mice, and germline deletion, we establish stathmin-2 to be essential for acquisition and maintenance of neurofilament-dependent structuring of axoplasm critical for maintaining diameter and conduction velocity of large-myelinated axons. Sustained stathmin-2 loss from an otherwise mature adult nervous system is demonstrated over a time course of eight months to initiate and drive motor neuron disease that includes 1) shrinkage in inter-neurofilament spacing that is required to produce a three-dimensional space filling array that defines axonal caliber, 2) collapse of mature axonal caliber with tearing of outer myelin layers, 3) reduced conduction velocity, 4) progressive motor and sensory deficits (including reduction of the pain transducing neuropeptide CGRP), and 5) muscle denervation. Demonstration that chronic stathmin-2 reduction is itself sufficient to trigger motor neuron disease reinforces restoration of stathmin-2 as an attractive therapeutic approach for TDP-43-dependent neurodegeneration, including the fatal adult motor neuron disease ALS.Competing Interest StatementThe authors have declared no competing interest.