The potential of a tumor cell to metastasize profoundly depends on its microenvironment, or "niche" interactions with local components. Tumor-associated-macrophages (TAMs) are the most abundant subpopulation of tumor stroma and represent a key component of tumor microenvironment. The dynamic interaction of cancer cells with neighboring TAMs actively drive cancer progression and metastatic transformation through intercellular signaling networks that need better elucidation. Thus, current study was planned for discerning paracrine communication networks operational between TAMs, and breast cancer cells with special reference to cancer cell invasion and dissemination to distant sites. Here, we report role of MIP-1β in enhancing invasive potential of metastatic breast cancer MDA-MB-231 and MDA-MB-468 cells. In addition, the poorly metastatic MCF-7 cells were also rendered invasive by MIP-1β. The MIP-1β-driven cancer cell invasion was dependent on upregulated expression levels of MYO3A gene, which encodes an unconventional myosin super-family protein harboring a kinase domain. Ex ovo study employing Chick-embryo-model and in vivo Syngenic 4T1/BALB/c mice-model further corroborated aforementioned in vitro findings, thereby substantiating their physiological relevance. Concordantly, human breast cancer specimen exhibited significant association between mRNA expression levels of MIP-1β and MYO3A. Both, MIP-1β and MYO3A exhibited positive correlation with MMP9, an established molecular determinant of cancer cell invasion. Higher expression of these genes correlated with poor survival of breast cancer patients. Collectively, these results point toward so far undisclosed MIP-1β/MYO3A axis being operational during metastasis, wherein macrophage-derived MIP-1β potentiated cancer cell invasion and metastasis via up regulation of MYO3A gene within cancer cells. Our study exposes opportunities for devising potential anti-metastatic strategies for efficient clinical management of breast cancer.

This study belongs to identification of suitable COVID-19 inhibitors<br><div><br></div><div>Coronavirus became pandemic very soon and is a potential threat to human lives across the globe. No approved drug is currently available therefore an urgent need has been developed for any antiviral therapy for COVID-19. For the molecular docking study, ten herbal molecules have been included in the current study. The three-dimensional chemical structures of molecules were prepared through ChemSketch 2015 freeware. Molecular docking study was performed using AutoDock 4.2 simulator and Discovery studio 4.5 was employed to predict the active site of target enzyme. Result indicated that all-natural molecules found in the active site of enzyme after molecular docking. Oxyacanthine and Hypericin (-10.990 and -9.05 and kcal/mol respectively) have shown good binding efficacy among others but Oxyacanthine was the only natural product which made some of necessary interactions with residues in the enzyme require for target inhibition. Therefore Oxyacanthine may be considered to be potential inhibitor of main protease enzyme of virus but need to be explored for further drug development process. <br></div>

Severe cases of COVID-19 are characterized by hyperinflammation induced by cytokine storm, ARDS leading to multiorgan failure and death. JAK-STAT signaling has been implicated in immunopathogenesis of COVID-19 infection under different stages such as viral entry, escaping innate immunity, replication, and subsequent inflammatory processes. Prompted by this fact and prior utilization as an immunomodulatory agent for several autoimmune, allergic, and inflammatory conditions, Jakinibs have been recognized as validated small molecules targeting the rapid release of proinflammatory cytokines, primarily IL-6, and GM-CSF. Various clinical trials are under investigation to evaluate Jakinibs as potential candidates for treating COVID-19. Till date, there is only one small molecule Jakinib known as baricitinib has received FDA-approval as a standalone immunomodulatory agent in treating critical COVID-19 patients. Though various meta-analyses have confirmed and validated the safety and efficacy of Jakinibs, further studies are required to understand the elaborated pathogenesis of COVID-19, duration of Jakinib treatment, and assess the combination therapeutic strategies. In this review, we highlighted JAK-STAT signalling in the pathogenesis of COVID-19 and clinically approved Jakinibs. Moreover, this review described substantially the promising use of Jakinibs and discussed their limitations in the context of COVID-19 therapy. Hence, this review article provides a concise, yet significant insight into the therapeutic implications of Jakinibs as potential anti-COVID agents which opens up a new horizon in the treatment of COVID-19, effectively.

Ethnopharmacological relevance:Alchornea laxiflora (Benth.) Pax &amp; K. Hoffm. (Euphorbiaceae) is an important traditional medicinal plant grown in tropical Africa. The stem, leaves, and root have been widely used in the folk medicine systems in Nigeria, Cameroon, South Africa, and Ghana to treat various ailments, including inflammatory, infectious, and central nervous system disorders, such as anxiety and epilepsy.Material and methods: The scientific name of the plant was validated using the “The Plant List,” “Kew Royal Botanic Gardens,” and Tropicos Nomenclatural databases. The literature search on A. laxiflora was performed using electronic search engines and databases such as Google scholar, ScienceDirect, PubMed, AJOL, Scopus, and Mendeley.Results: To the best of our knowledge, no specific and detailed review has been reported on A. laxiflora. Consequently, this review provides an up-to-date systematic presentation on ethnobotany, phytoconstituents, pharmacological activities, and toxicity profiles of A. laxiflora. Phytochemical investigations disclosed the presence of important compounds, such as alkaloids, flavonoids, phenolics, terpenoids, and fatty acids. Furthermore, various pharmacological activities and traditional uses reported for this botanical drug were discussed comprehensively.Conclusion: This systemic review presents the current status and perspectives of A. laxiflora as a potential therapeutic modality that would assist future researchers in exploring this African botanical drug as a source of novel drug candidates for varied diseases.

Objective: The aim of the present study was to assess bioactive compounds found in Tulsi as potential COVID-19 Mpr °inhibitor using molecular docking and to provide scientific justification in term of its active ingredient to target protein for prevention and symptomatic treatment of COVID-19. Methods: COVID-19 Mpr °was docked with eight phytochemicals of Ocimum sanctum Linn. Using Autodock 4.2. Determination of active site and visualization of molecular interactions between ligands and target enzyme was done by Biovia Discovery Studio 4.5. Results: Our result demonstrates that Vicenin, Caryophyllene, Cirsimaritin, Isothymusin and Isothymonin have a better binding affinity to target enzyme. However, only Vicenin exhibited better binding energy i.e.-7.02 kcal/mol to COVID-19 Main protease among other phytochemicals through some responsible interactions to inhibit the replication of SARS-CoV-2 in the human body, whereas Caryophyllene and Cirsimaritin exhibited similar binding affinity i.e.-6.46 kcal/mol but different interactions with target enzyme. Conclusion: Tulsi (Ocimum sanctum Linn.) is a preeminent traditional drug of Ayurveda for prophylaxis and treatment of various ailments, including respiratory disorders like cough, cold and flu. With no specific therapies available, reevaluating and repurposing traditional drugs could be an effective approach for the prevention and treatment of SARS-CoV-2 infection. Therefore our study provides scientific evidence for the potential use of Tulsi as an adjunct therapy for the prevention and symptomatic treatment of COVID-19. However, further in vitro and in vivo studies should be conducted to validate use of proposed compounds in drug discovery and as therapeutics against COVID-19.

This study belongs to identification of suitable COVID-19 inhibitors<br><div><br></div><div>Coronavirus became pandemic very soon and is a potential threat to human lives across the globe. No approved drug is currently available therefore an urgent need has been developed for any antiviral therapy for COVID-19. For the molecular docking study, ten herbal molecules have been included in the current study. The three-dimensional chemical structures of molecules were prepared through ChemSketch 2015 freeware. Molecular docking study was performed using AutoDock 4.2 simulator and Discovery studio 4.5 was employed to predict the active site of target enzyme. Result indicated that all-natural molecules found in the active site of enzyme after molecular docking. Oxyacanthine and Hypericin (-10.990 and -9.05 and kcal/mol respectively) have shown good binding efficacy among others but Oxyacanthine was the only natural product which made some of necessary interactions with residues in the enzyme require for target inhibition. Therefore Oxyacanthine may be considered to be potential inhibitor of main protease enzyme of virus but need to be explored for further drug development process. <br></div>

Background: Parkinson’s disease (PD) is a neurodegenerative syndrome defined by a variety of motor, cognitive, and psychomotor dysfunctions. The current pharmaceutical treatment focuses on treating the condition's symptoms. They are primarily concerned with reducing illness symptoms or avoiding dopamine metabolism. As our understanding of disease pathogenesis improves, new therapeutic approaches emerge. Objective: This article aims to describe the standard Parkinson's medications based on symptoms and requirements. It emphasizes recent advancements in symptomatic therapy for motor indications and achievements in the research and clinical testing of medicines that promise to enable disease modification in patients with already-manifest PD. Methods: Information for this paper was found by looking through Google Scholar and reading several research and review articles from Bentham Science, Science Direct, Elsevier, Frontiers, Taylor & Francis, and other publishers. Result: Parkinson's disease therapeutic interventions are now limited to symptomatic therapy, mostly in dopaminergic medications and deep brain stimulation (DBS). They have the potential to deliver great therapeutic progress, yet they can also have serious drawbacks that decrease a patient's quality of life. The progress of pluripotent stem cell therapies and genome engineering procedures has sparked renewed hope for the treatment of a wide range of human illnesses, particularly genetic abnormalities. Conclusion: The current Parkinson's therapy trends are successful and continually evolving, with several drugs currently undergoing clinical trials. As these new therapies constantly coming out and can be used together, they will likely change how Parkinson's disease is treated in the coming years.

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