Background/Objectives:N-Myristoyltransferase inhibitors (NMTi) represent a novel antiviral strategy against mammarenaviruses such as Lassa and Junin viruses. The Z matrix protein inhibits viral ribonucleoprotein (vRNP) activity in a dose-dependent manner. Here, we investigated whether Z-mediated vRNP inhibition depends on Z myristoylation or oligomerization.Methods:We used HEK293T cells transfected with wild-type (WT) or G2A-mutated Z constructs in LCMV minigenome (MG) assays. Cells were treated with the NMTi IMP-1088 and the proteasome inhibitor MG132. Z protein expression, vRNP activity, and VLP production were analyzed by immunofluorescence, western blotting, and colocalization analyses.Results:IMP-1088 treatment led to proteasome-mediated degradation of Z, reducing its inhibition of vRNP activity, which was restored by MG132. The non-myristoylated Z G2A mutant retained vRNP inhibitory activity but showed impaired oligomerization and budding capacity. These findings demonstrate that Z-mediated vRNP inhibition is independent of myristoylation and oligomerization.Conclusions:Z myristoylation and oligomerization are not required for its inhibitory vRNP activity. Targeting Z myristoylation with NMTi impairs virus assembly and budding without affecting Z-mediated inhibition of vRNP activity, supporting the development of NMTi as a promising broad-spectrum antiviral strategy against mammarenaviruses.

Background/Objectives: Burns are a prevalent health concern that manifest on the skin’s surface or within organs due to various traumas and necessitate prompt intervention. The healing process of the skin involves a sequence of time-dependent events, commencing with the activation of growth factors and culminating in the expression of various genes. To expedite the healing process of burn wounds, there is a need to develop biodegradable materials and new technologies that are compatible with the skin. Methods: In this study, the roles of tilapia (TL, Oreochromis niloticus) fish skin in burn wound treatment processes were investigated. TL or TL-alginate hydrogels (AGTL) were applied to a burn wound created in Sprague Dawley rats for 7 and 14 days. Following the administration of treatment, the levels of hydroxyproline, a critical element in tissue reorganization, along with the gene expression levels of COL1A1, COL3A1, MMP-2, and MMP-9, and the protein expression levels of MMP-2 and MMP-9 were evaluated. Results: Wound closure processes were faster in AGTL-groups compared to TL-groups, and hydroxyproline levels were found to be higher. While the increase in MMP-2 levels was less, the increase in MMP-9 gene and protein levels was greater in the AGTL-group. Concurrently, COL1A1 levels decreased over 14 days, while COL3A1 levels increased in the AGTL-group. Conclusions: Consequently, it was determined that the biological substances in the TL structure, in conjunction with alginate, were effective in the healing and reorganization of the wound tissue. This finding suggests that tilapia may provide a valuable source of insights for future studies aimed at developing effective wound dressings for wound tissues.

The COVID-19 pandemic, instigated by the emergence of the novel coronavirus, SARS-CoV-2, created an incomparable global health crisis. Due to its highly virulent nature, identifying potential therapeutic agents against this lethal virus is crucial. PLpro is a key protein involved in viral polyprotein processing and immune system evasion, making it a prime target for the development of antiviral drugs to combat COVID-19. To expedite the search for potential therapeutic candidates, this review delved into computational studies. Recent investigations have harnessed computational methods to identify promising inhibitors targeting PLpro, aiming to suppress the viral activity. Molecular docking techniques were employed by researchers to explore the binding sites for antiviral drugs within the catalytic region of PLpro. The review elucidates the functional and structural properties of SARS-CoV-2 PLpro, underscoring its significance in viral pathogenicity and replication. Through comprehensive all-atom molecular dynamics (MD) simulations, the stability of drug–PLpro complexes was assessed, providing dynamic insights into their interactions. By evaluating binding energy estimates from MD simulations, stable drug–PLpro complexes with potential antiviral properties were identified. This review offers a comprehensive overview of the potential drug/lead candidates discovered thus far against PLpro using diverse in silico methodologies, encompassing drug repurposing, structure-based, and ligand-based virtual screenings. Additionally, the identified drugs are listed based on their chemical structures and meticulously examined according to various structural parameters, such as the estimated binding free energy (ΔG), types of intermolecular interactions, and structural stability of PLpro–ligand complexes, as determined from the outcomes of the MD simulations. Underscoring the pivotal role of targeting SARS-CoV-2 PLpro in the battle against COVID-19, this review establishes a robust foundation for identifying promising antiviral drug candidates by integrating molecular dynamics simulations, structural modeling, and computational insights. The continual imperative for the improvement of existing drugs and exploring novel compounds remains paramount in the global efforts to combat COVID-19. The evolution and management of COVID-19 hinge on the symbiotic relationship between computational insights and experimental validation, underscoring the interdisciplinary synergy crucial to this endeavor.

Background: Levels of chronic inflammation, oxidative stress, and neurotransmitter availability are altered in depressed patients and can be used as biological markers. This study aimed to analyze these markers in female Wistar rats under chronic inflammation induced by E. coli lipopolysaccharide (LPS), treated with aqueous extract of A. gratissima and rutin, the major flavonoid of its extract. Methods: Thirty female Wistar rats under a chronic inflammatory regimen induced by 1 mg/kg i.p. of LPS were divided into six experimental groups: control (1), treated with fluoxetine 5 mg/kg (2), rutin at 50 mg/kg (3) or 100 mg/kg (4), aqueous extract of A. gratissima 100 mg/kg (5), and co-treatment with 50 mg/kg of extract and 10 mg/kg of rutin (6). Treatments were administered by gavage for 15 days. Results: Oxidative damage to proteins and lipids was lower in group 6 compared to group 2. Pro- and anti-inflammatory cytokines increased in group 1 but not in group 2, indicating a relationship with depression. Similar effects were observed in the treated groups, showing no significant differences from group 2. Neurotransmitter levels of dopamine and serotonin were low in group 1, and all treatments effectively increased them. Additionally, A. gratissima extract at 100 ppm increased locomotor activity in planarians. Conclusions: This study demonstrates the effectiveness of the LPS induction model in subacute experimental designs and the potential antidepressant effect of the treatments due to their antioxidant and anti-inflammatory properties, and ability to increase neurotransmitter levels.

Pulmonary arterial hypertension (PAH) is a progressive disorder caused by the narrowing of small blood vessels in the lungs, which, in the absence of therapies, leads to right heart failure and premature death. No cure for this devastating disorder is known. Current management therapies aim to improve symptoms, and hence, there is a need to identify novel therapeutic interventions. The major objectives of this review are to critically evaluate current treatment strategies and highlight the challenges and prospects of established drugs and natural products for the resolution of PAH.

Nitric oxide (•NO), a diffusible free radical, is an intercellular messenger, playing a crucial role in several key brain physiological processes, including in neurovascular coupling (NVC). In the brain, glutamatergic activation of the neuronal nitric oxide synthase (nNOS) enzyme constitutes its main synthesis pathway. However, when oxygen (O2) supply is compromised, such as in stroke, ischemia, and aging, such •NO production pathway may be seriously impaired. In this context, evidence suggests that, as already observed in the gastric compartment, the reduction of nitrite by dietary compounds (such as ascorbate and polyphenols) or by specific enzymes may occur in the brain, constituting an important rescuing or complementary mechanism of •NO production. Here, using microsensors selective for •NO, we show that nitrite enhanced the •NO production in a concentration-dependent manner and in the presence of ascorbate evoked by N-methyl-D-aspartate (NMDA) and glutamate stimulation of rat hippocampal slices. Additionally, nitrite potentiated the •NO production induced by oxygen-glucose deprivation (OGD). Overall, these observations support the notion of a redox interaction of ascorbate with nitrite yielding •NO upon neuronal glutamatergic activation and given the critical role of NO as the direct mediator of neurovascular coupling may represents a key physiological mechanism by which •NO production for cerebral blood flow (CBF) responses to neuronal activation is sustained under hypoxic/acidic conditions in the brain.

The 2019 oil spill was considered the largest environmental disaster in the Brazilian Northeastern coast. It was associated with mostly ineffective government actions, thus intensifying historical vulnerabilities faced by local populations. We aimed to analyze the environmental conflicts and injustices and the socio-environmental, economic, and health vulnerabilities arising from the oil spill, considering the COVID-19 pandemic, impacting artisanal fishing communities of the Northeastern coast. A document-based, qualitative, cross-sectional research was carried out between September 2019 and October 2022, in open access secondary databases, and using field diaries from research of the Environmental Health and Work Laboratory (LASAT) of the Aggeu Magalhães Institute of the Oswaldo Cruz Foundation. The disaster caused situations of injustice and environmental conflicts that had negative repercussions in the territories with socioeconomic impacts, on the environment, and on the health of the population. The entire marine environment was affected, resulting in physical and chemical alterations. The health vulnerabilities faced by local people were intensified, influencing the social determination of the health–disease process. The local economy was extremely affected, generating job insecurity and several socio-cultural problems. It is essential to build environmental and health diagnoses for remedial measures in disasters such as the oil spill.

Infection and sepsis remain among the leading causes of neonatal mortality. The susceptibility of newborns to infection can be attributed to their immature immune system. Regarding immune response, monocytes represent a numerically minor population of leukocytes. However, they contribute to a variety of immunological demands, such as continuous replenishment of resident macrophages under non-infectious conditions and migration to inflamed sites where they neutralize pathogens and secrete cytokines. Further functions include the presentation of antigens and T-cell activation. Cytokines coordinate host responses to bacterial and viral infections and orchestrate ongoing physiological signaling between cells of non-immune tissues. A critical event is the skewing of the cytokine repertoire to achieve a resolution of infection. In this regard, monocytes may hold a key position as deciders in addition to their phagocytic activity, securing the extinction of pathogens to prevent broader organ damage by toxins and pro-inflammatory reactions. Neonatal monocytes undergo various regulatory and metabolic changes. Thus, they are thought to be vulnerable in anticipating pro-inflammatory conditions and cause severe progressions which increase the risk of developing sepsis. Furthermore, clinical studies have shown that exposure to inflammation puts neonates at a high risk for adverse pulmonary, immunological and other organ developments, which may result in multiorgan disease. This review discusses significant functions and impairments of neonatal monocytes that are decisive for the outcome of bacterial infections.

Bipolar Disorder (BD), a chronic mental illness, does not have an ideal treatment, and patients with BD have a higher chance of being diagnosed with alcohol abuse, liver disease, and diabetes. The goal of treatment is to prevent a relapse in BD episodes and find a new treatment. The research here looks at the genetics of BD and ignores environmental factors, as they are subjective. Therapy treats known environmental triggers and stressors and explores methods to reduce them. However, therapy alone cannot fully alleviate the symptoms of BD. My research employs text-mining as a primary strategy to obtain relevant genes and drugs pertaining to BD. The main gene involved is the Brain-Derived Neurotrophic Factor (BDNF). Popular drugs currently used for treatment of BD are Lithium and Carbamazepine. Using CMapPy to look at gene expression data, one sees a relationship between the two drug therapies and BDNF. Lithium fails to treat mania and Carbamazepine fails to treat depression, relatively speaking. When comparing gene expression data of Lithium and Carbamazepine with Ketamine, a newer therapy for BD, Ketamine, raises the BDNF level, keeps it elevated, and effectively controls BD episodes. Ketamine does not have the shortcomings that Lithium and Carbamazepine have. Next steps would include conducting a clinical trial with the hopeful application of Ketamine as a new treatment for BD.

The urgent need to fight the COVID-19 pandemic has impressively stimulated the efforts of the international scientific community, providing an extraordinary wealth of studies. After the sequence of the virus became available in early January 2020, safe and effective vaccines were developed in a time frame much shorter than everybody expected. However, additional studies are required since viral mutations have the potential of facilitating viral transmission, thus reducing the efficacy of developed vaccines. Therefore, improving the current laboratory testing methods and developing new rapid and reliable diagnostic approaches might be useful in managing contact tracing in the fight against both the original SARS-CoV-2 strain and the new, potentially fast-spreading CoV-2 variants. Mass Spectrometry (MS)-based testing methods are being explored, with the challenging promise to overcome the many limitations arising from currently used laboratory testing assays. More specifically, MALDI-MS, since its advent in the mid 1980s, has demonstrated without any doubt the great potential to overcome many unresolved analytical challenges, becoming an effective proteomic tool in several applications, including pathogen identification. With the aim of highlighting the challenges and opportunities that derive from MALDI-based approaches for the detection of SARS-CoV-2 and its variants, we extensively examined the most promising proofs of concept for MALDI studies related to the COVID-19 outbreak.