The Nonlinearity of Working Capital and Cross-Sectional Stock Returns: Does Financial Constraints Matter?

This study is the first to examine the impacts of working capital (WC) and financial constraints on cross-sectional stock returns in Taiwan. The findings indicate a non-linear relationship between WC and stock returns. Moreover, the nonlinearity between WC and cross-sectional stock returns is robust after controlling for financial constraints, risk, and growth factors, before the Covid-19 pandemic. In contrast, there is no evidence of nonlinearity between WC and stock returns throughout the Covid-19 outbreak. In addition, the study shows that any deviations from the minimum WC level enhance the stock returns cross-sectionally. It is found that a positive Deviation effect exists in the Taiwan stock exchange before the Covid-19 pandemic by employing portfolio sorting methodologies. The return difference of the long buying highest Deviation and short selling lowest Deviation portfolios earn from 0.6% to 0.9% per month after controlling for financial constraints, risks, and growth factors. Interestingly, it is determined that the deviation effect becomes negative for small stocks during the Covid-19 pandemic, implying that investors prefer small stocks to maintain minimum working capital. The results support the trade-off theory and liquidity preference theory. Finally, the study provides insights into working capital management for managers, and investment strategies for investors during the pandemic.

Colostrum ingredients, its nutritional and health benefits - an overview

This review focused on compiling, summarizing, updating the information available on the colostrum and its health benefits. Colostrum is the first milk secreted by the mammary gland of female mammals immediately after birth during the first few days, and its composition differs from the mature milk. It ensures immune support for newborns in the early stages of life. It is a divine immune gift from the Creator. Mammalian colostrum contains unique components rich in nutritional macronutrients (proteins, fat, carbohydrates) and micronutrients (vitamins, minerals, antioxidants) and many bioactive substances like antimicrobial factors (Igs, LF, LP, LZ, cytokines) and growth factors (EGF, TGFalpha and beta, IGF-1 and 2, FGF, PDGF, GH), which are necessary to stimulate the immune systems that newborns need for health and survival life. Physicochemical composition changes dramatically in the first few days that distinguish it from mature milk. This reverses an essential difference in their biological function as fractional sources or for health-promotion. So it is considered one of the best natural food supplements consumed within various life stages. Colostrum is used to treat cancer, AIDS, polio, heart disease, and rheumatoid arthritis. Hyper-immune colostrum or milk collected from cows immunized by SARS-CoV-2, it can grant protection short-term from infection in humans and can be used as an alternative way to produce specific antibodies against CoVID-19 until effective excess vaccines against new mutations can be available. Likewise, colostrum and its components contribute as a non-drug alternative to the clinical management of CoVID-19. Also, lactoferrin and its supplements are effective in preventing and treating people with coronavirus infection. Therefore, due to these previous multiple functions, colostrum is considered as a natural food, called miracle immune milk, and used as a medicine.Copyright © 2022 The Author

Marketing Strategy and Performance in Tourism Industry: SMART Tourism Development in Madura Island

This study aims to determine the growth factors, strategies, and performance of SMART. SMART stands for Specific, Measurable, Achievable, Relevant, and Time-Bound in the form of an effective process for determining and achieving business goals. The research design is a mix of methods to collect, process, and analyze data systematically and directly so that research can be carried out properly. Our findings reveal that the actual condition of the recovery of tourism industry, especially in Bangkalan, Sumenep, and Pamekasan regencies is getting better. The main challenge for the post-pandemic tourism industry is to promote local tourism on the international stage. It can be concluded that the SMART tourism framework can provide opportunities for businesses to determine their goals in facing the challenges of the tourism industry. Also, these findings reveal a lack of critical literature examining the assumptions of smart tourism and questioning its feasibility and positive experiential, economic and social impacts on local communities. This study proposes a research agenda that is far from comprehensive by understanding SMART's tourism potential and possible shortcomings and becomes a recommendation for government policies in the context of restoring the tourism industry in Indonesia.

Todim-Vikor Methods with Pythagorean Fuzzy Information Based Emergency Decision Support Model for Economic Growth Factor Selection

Because India's economy has shrunk to a low level during COVID-19, building an emergency decision support model (EDSM) for economic growth factors is the main objective of this study. We develop the TODIM-VIKOR method under Pythagorean fuzzy information. For dealing with comparison problems, the Pythagorean fuzzy scoring function is presented. We also include a new entropy metric for assessing the degree of fuzziness in PyFS. We also present a new Jensen Shannon divergence metric for PyFS that can be used to compare the discrimination information of two PyFSs. In this article, we introduced entropy and divergence measures to derive objective weight in the TODIM-VIKOR approach. Establishes a novel emergency decision making (EDM) strategy under the Pythagorean fuzzy atmosphere, using economic growth considerations. We used TODIM to determine the overall dominance degree, which takes into account the bounded rationality of decision makers, and VIKOR to calculate the compromise ranking of alternatives. © 2023 IEEE.

The Relationship Between Coronavirus Disease-2019-Positive Patients and Plasma Interleukins and Transforming Growth Factor-γ Levels

Objective: The aim of this study is to reveal the relationship between the cytokine plasma levels and symptoms of coronavirus disease-2019 (COVID-19)-positive patients, which is characterized by serious respiratory syndromes. Materials and Methods: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-positive patients were evaluated in four groups. Group 1 patients had no symptoms. Group 2 patients were mildly symptomatic. Group 3 patients had multiple symptoms. Group 4 patients had all symptoms of acute respiratory distress syndrome. Analysis of interleukin (IL)-17A, transforming growth factor-γ1 (TGF-γ1), and IL-6 concentrations in plasma samples taken from patients were examined by enzyme-linked immunosorbent assay method. Results: IL-17A levels were increased in parallel with the clinical condition in all patients. TGF-γ1 was only observed in patients in Groups 3 and 4, and IL-6 was only observed in Group 4 patients. Conclusion: It is known that many cytokines are involved in the development of different viral infections and viral invasion always triggers an inflammatory response. The profile of inflammatory markers may be used to classify COVID-19 patients. In conclusion of this study, it is suggested that the level of cytokines which is changed according to the patient's clinical status should be used to evaluate the response of SARS-CoV-2 treatment. IL-17A, TGF-γ1, and IL-6 concentrations in plasma levels could be good prognostic indicators of COVID-19. [ FROM AUTHOR]

TGF-beta 2 enriched formula as oral nutritional supplement in patients hospitalized for COVID-19: A preliminary observational study

BACKGROUND: SARS-COV 2 turned in a global epidemic since January 2020. It is able to directly stimulate the release of proinflammatory cytokines (cytokine storm) and, affecting enterocytis, dysregulates intestinal permeability likewise Inflammatory Bowel Diseases. According to Guidelines, nutritional support in COVID-19 patients is relevant in a perspective of a fast recovery. Aim of this study is to propose in SARS-COV2 patients an early nutritional support using a polymeric-TGF-beta2 containing formula, with immunoregulatory properties specific for bowel disease, evaluating its effects on systemic inflammation and protein energy malnutrition. METHOD(S): COVID-19 patients hospitalized in Santa Maria Hospital of Terni and in Madonna delle Grazie Hospital of Matera (March-December 2020) were enrolled. The protocol consists in supplying 150 gr of nutritional formula powder (750 kcal/day). Values of serum prealbumin, transferrin, C-reactive protein and Lymphocyte count were collected at baseline and every week. Data were compared to a untreated sample of inpatients. RESULT(S): TGF-beta2 containing formula use seems to be associated to a lower needing and longer time free from steroid therapy, increasing of prealbumin and transferrin values and overall with a better outcome in exposed patients;higher values of serum prealbumin seemed to be associated with lower CRP. It does not induce gastrointestinal discomfort or worsen gastrointestinal symptoms. CONCLUSION(S): TGF-beta2 containing formula represents a valid nutritional support in COVID-19, preventing sarcopenia associated to hypercatabolic status and modulating inflammatory response probably thanks to specific properties of its nutritional components. This is only a preliminary observation: further investigations are on-going, involving several Italian Centers. Copyright © 2022-IOS Press. All rights reserved.

Predictive model for BNT162b2 vaccine response in cancer patients based on blood cytokines and growth factors.

Background: Patients with cancer, especially hematological cancer, are at increased risk for breakthrough COVID-19 infection. So far, a predictive biomarker that can assess compromised vaccine-induced anti-SARS-CoV-2 immunity in cancer patients has not been proposed. Methods: We employed machine learning approaches to identify a biomarker signature based on blood cytokines, chemokines, and immune- and non-immune-related growth factors linked to vaccine immunogenicity in 199 cancer patients receiving the BNT162b2 vaccine. Results: C-reactive protein (general marker of inflammation), interleukin (IL)-15 (a pro-inflammatory cytokine), IL-18 (interferon-gamma inducing factor), and placental growth factor (an angiogenic cytokine) correctly classified patients with a diminished vaccine response assessed at day 49 with >80% accuracy. Amongst these, CRP showed the highest predictive value for poor response to vaccine administration. Importantly, this unique signature of vaccine response was present at different studied timepoints both before and after vaccination and was not majorly affected by different anti-cancer treatments. Conclusion: We propose a blood-based signature of cytokines and growth factors that can be employed in identifying cancer patients at persistent high risk of COVID-19 despite vaccination with BNT162b2. Our data also suggest that such a signature may reflect the inherent immunological constitution of some cancer patients who are refractive to immunotherapy.

Vascular Endothelial Growth Factor Receptor 2: Molecular Mechanism and Therapeutic Potential in Preeclampsia Comorbidity with Human Immunodeficiency Virus and Severe Acute Respiratory Syndrome Coronavirus 2 Infections.

This review explored the role of vascular endothelial growth factor receptor-2 (VEGFR-2) in the synergy of preeclampsia (PE), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Downregulation of VEGFR-2 in PE promotes endothelial dysfunction and prevents endothelial cell (EC) migration, proliferation, and differentiation. The HIV-1 accessory protein, tat (trans-activator of transcription), prevents VEGFR-2 signaling via the vascular endothelial growth factor A (VEGF-A) ligand. Combined antiretroviral therapy (cART) may cause immune reconstitution, impaired decidualization, and endothelial injury, thus may be a risk factor for PE development. The VEGF/VEGFR-2 interaction may be associated with SARS-CoV-2-related pulmonary oedema. Endothelial dysfunction and heightened inflammation are both associated with PE, HIV, and SARS-CoV-2 infection; therefore, it is plausible that both characteristics may be exacerbated in the synergy of these events. In addition, this review explored microRNAs (miR) regulating VEGFR-2. An overexpression of miR-126 is evident in PE, HIV, and SARS-CoV-2 infection; thus, modulating the expression of miR-126 may be a therapeutic strategy. However, the involvement of microRNAs in PE, HIV, and SARS-CoV-2 infection needs further investigating. Since these conditions have been evaluated independently, this review attempts to predict their clinical manifestations in their synergy, as well as independently; thereby providing a platform for early diagnosis and therapeutic potential in PE, HIV, and SARS-CoV-2 infection.

With the Continuing Increase in Sub-Saharan African Countries, Will Sustainable Development of Goal 1 Ever Be Achieved by 2030?

The poor in Sub-Saharan Africa (SSA) are in a worse predicament than their counterparts in other regions. The goal of this study was to establish the key drivers of poverty in SSA by looking at how economic variables affect growth and poverty. Data from ten SSA nations—upper-middle-income countries (UMIC), lower-middle-income countries (LMIC), and low-income countries (LIC)—were analyzed based on historical values from 2015 to 2019. From the six economic variables studied, the best model reveals that 78% of the differences in poverty can be accounted for using a methodical, statistical approach. Poverty and unemployment rates have a substantial positive relationship (p = 0.001662). The gross domestic product (GDP) growth rate and poverty have a slight link, which is significant at the 10% level (p = 0.067) but is not a significant contributor to poverty alleviation. The secondary school enrolment rate has no bearing on poverty variation (p = 0.33). Increased GDP does not necessarily correspond to poverty reduction. Unemployment, on the other hand, is a major contributor to poverty in the region. Moreover, education (secondary school ennoblement) plays a less important role in reducing poverty, whereas per capita personal consumer spending and GDP growth rate have a bigger impact on poverty reduction. The proposed theoretical and numerical model works on general indicators and trends;it does not guarantee that people in the UMIC, LMIC, and LIC countries may not fall below the international poverty line ($1.90 per day). The poverty rates are predicted to climb by more than 2% by 2030, postponing poverty elimination in the SSA region by almost five years. This signifies that more than half of the SSA population will remain poor.

Role of Innate and Adaptive Cytokines in the Survival of COVID-19 Patients.

SARS-CoV-2 is a new coronavirus characterized by a high infection and transmission capacity. A significant number of patients develop inadequate immune responses that produce massive releases of cytokines that compromise their survival. Soluble factors are clinically and pathologically relevant in COVID-19 survival but remain only partially characterized. The objective of this work was to simultaneously study 62 circulating soluble factors, including innate and adaptive cytokines and their soluble receptors, chemokines and growth and wound-healing/repair factors, in severe COVID-19 patients who survived compared to those with fatal outcomes. Serum samples were obtained from 286 COVID-19 patients and 40 healthy controls. The 62 circulating soluble factors were quantified using a Luminex Milliplex assay. Results. The patients who survived had decreased levels of the following 30 soluble factors of the 62 studied compared to those with fatal outcomes, therefore, these decreases were observed for cytokines and receptors predominantly produced by the innate immune system-IL-1α, IL-1α, IL-18, IL-15, IL-12p40, IL-6, IL-27, IL-1Ra, IL-1RI, IL-1RII, TNFα, TGFα, IL-10, sRAGE, sTNF-RI and sTNF-RII-for the chemokines IL-8, IP-10, MCP-1, MCP-3, MIG and fractalkine; for the growth factors M-CSF and the soluble receptor sIL2Ra; for the cytokines involved in the adaptive immune system IFNγ, IL-17 and sIL-4R; and for the wound-repair factor FGF2. On the other hand, the patients who survived had elevated levels of the soluble factors TNFß, sCD40L, MDC, RANTES, G-CSF, GM-CSF, EGF, PDGFAA and PDGFABBB compared to those who died. Conclusions. Increases in the circulating levels of the sCD40L cytokine; MDC and RANTES chemokines; the G-CSF and GM-CSF growth factors, EGF, PDGFAA and PDGFABBB; and tissue-repair factors are strongly associated with survival. By contrast, large increases in IL-15, IL-6, IL-18, IL-27 and IL-10; the sIL-1RI, sIL1RII and sTNF-RII receptors; the MCP3, IL-8, MIG and IP-10 chemokines; the M-CSF and sIL-2Ra growth factors; and the wound-healing factor FGF2 favor fatal outcomes of the disease.

DEMONSTRATING HOW A HIGH-GROWTH FRAMEWORK COULD BE USED TO ASSIST A SOCIAL ENTERPRISE TO IDENTIFY GROWTH FACTORS AND IMPROVE SUSTAINABILITY

Maatskaplike ondernemings is kritieke rolspelers in ekonomiese groei en dienslewering. Hierdie artikel stel 'n instrument voor wat help om die aspekte te identifiseer wat die volhoubaarheid van maatskaplike ondernemings bei'nvloed. Die instrument is gebaseer op 'n raamwerk wat hoě groei-faktore identifiseer en gebruik die "CRISP-DM" (Kruis-industrie standaard proses vir data ontginning) metodologie en wedersydse inligtingsanalise om 'n praktiese hulpmiddel te ontwikkel wat maatskaplike ondernemings se lewensvatbaarheid en volhoubaarheid ondersteun. Die instrument is toegepas op 'n gevallestudie om te toon hoe praktisyns en sake-eienaars dit kan benut. Boonop wys hierdie artikel ook hoe vakkundiges bykomende insigte kan verkry uit data wat voorheen deur 'n ander metodologie ontleed is.Alternate :Social enterprises are critical players in economic growth and service delivery. This article presents a tool that helps to identify the aspects that affect the sustainability of social enterprises. The tool is based on a framework that identifies high-growth factors and that uses the CRISPDM (Cross-industry standard process for data mining) methodology and mutual information analysis to develop a practical tool to support social enterprises' viability and sustainability. The tool was applied to a case study to exemplify how practitioners and business owners could use it. In addition, this article shows how scholars could gain additional insights from data that had been previously analysed using a different methodology.

Cytokine Storm Signature in Patients with Moderate and Severe COVID-19.

Hypercytokinemia, found in SARS-CoV-2 infection, contributes to multiple organ dysfunctions with acute respiratory distress syndrome, shock etc. The aim of this study was to describe cytokine storm signatures in patients with acute COVID-19 and to investigate their influence on severity of the infection. Plasma levels of 47 cytokines were investigated in 73 patients with moderate and severe COVID-19 (41 and 32, respectively) and 11 healthy donors (HD). The most elevated levels comparing patients and the HD were observed for seven pro-inflammatory cytokines (IL-6, IL-8, IL-15, IL-18, IL-27, IFNγ, TNFα), three chemokines (GROα, IP-10, MIG), two anti-inflammatory cytokines (IL-1RA, IL-10), and two growth factors (G-CSF, M-CSF). The patients with severe disease had significantly higher levels of FGF-2/FGF-basic, IL-1ß, and IL-7 compared to the HD. The two groups of patients differed from each other only based on the levels of EGF, eotaxin, and IL-12 p40. Pneumonia lung injury, characterized by computer tomography, positively correlated with levels of EGF, IP-10, MCP-3 levels and negatively with IL-12 p40. Pro-inflammatory factors including IL-6, TNFα, and IP-10 negatively correlated with the frequency of the circulating T-helper17-like cells (Th17-like) and follicular Th cells that are crucial to develop SARS-CoV-2-specific plasma cells and memory B cells. Obtained data on the cytokine levels illustrate their influence on progression and severity of COVID-19.

Pharmacological activities of Curcumin: An update

In the past few years, multiple drugs have been produced from traditional raw materials and recent pandemic disease COVID-19 once again research on this matter is being conducted to determine potential therapeutic purposes of different Ayurvedic Indian medicines and herbs. One such medicinal herb is Curcuma longa. Curcumin is strong antioxidant, anti-inflammatory, antispasmodic, antiangiogenic, anti-carcinogenic, as shown by multiple in vitro and in vivo studies. The action of the growth factor receptors is inhibited by curcumin. The anti-inflammatory effect of curcumin is obtained on the cytokines, proteolytic enzymes, eicosanoids, and lipid mediators. The superoxide radicals, nitric oxide and hydrogen peroxide, are sifted by curcumin, while lipid peroxidation is inhibited. Such properties of the compound thus form the foundation for its various therapeutic and pharmacological effects could also hold antiviral properties including COVID-19. The aim of this research is to summarize the updated pharmacological activities of curcumin.

Increased VEGF-A Expression is Associated with Covid-19 Disease Progression

The global pandemic caused by the SARS-COV2 virus persists. Coronaviruses causing COVID-19 disease interact with ACE-2 receptors and penetrate host cells by endocytosis. This process can lead to a rapid release of proinflammatory mediators, which is one of the factors responsible for the development of one serious complication of the disease, acute respiratory distress syndrome. The altered regulation of specific cytokines and growth factors that affect various physiological processes, such as immune responses, can exacerbate the progression of viral diseases and contribute to the pathogenesis of COVID-19 disease. The aim of this study was to compare relative expression of selected growth factors (IGF-1, FGF-2, VEGF-A) in plasma samples from patients with and without COVID-19 disease. To measure relative expression RT-qPCR was used. Our data showed that relative expressions of selected growth factors in 3 groups of patients (6 patients cured from the disease, 6 patients who succumbed to the disease, 6 COVID-19 negative patients) are altered. The relative expression of VEGF-A was increased in patients who died of COVID-19 disease. A decrease in the relative expression of FGF-2 was observed in patients who overcame the disease compared to patients who succumbed to the disease. Differences in relative expression of IGF-1 were very slight in all three patient groups. These changes all suggest the importance of examining specific growth factors and their levels in relation to the development of COVID-19 disease. [ FROM AUTHOR] Copyright of Acta Facultatis Pharmaceuticae Universitatis Comenianae is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Colostrum Ingredients, its Nutritional and Health Benefits - An Overview

This review focused on compiling, summarizing, updating the information available on the colostrum and its health benefits. Colostrum is the first milk secreted by the mammary gland of female mammals immediately after birth during the first few days, and its composition differs from the mature milk. It ensures immune support for newborns in the early stages of life. It is a divine immune gift from the Creator. Mammalian colostrum contains unique components rich in nutritional macronutrients (proteins, fat, carbohydrates) and micronutrients (vitamins, minerals, antioxidants) and many bioactive substances like antimicrobial factors (Igs, LF, LP, LZ, cytokines) and growth factors (EGF, TGFα and β, IGF-1 and 2, FGF, PDGF, GH), which are necessary to stimulate the immune systems that newborns need for health and survival life. Physicochemical composition changes dramatically in the first few days that distinguish it from mature milk. This reverses an essential difference in their biological function as fractional sources or for health-promotion. So it is considered one of the best natural food supplements consumed within various life stages. Colostrum is used to treat cancer, AIDS, polio, heart disease, and rheumatoid arthritis. Hyper-immune colostrum or milk collected from cows immunized by SARS-CoV-2, it can grant protection short-term from infection in humans and can be used as an alternative way to produce specific antibodies against CoVID-19 until effective excess vaccines against new mutations can be available. Likewise, colostrum and its components contribute as a non-drug alternative to the clinical management of CoVID-19. Also, lactoferrin and its supplements are effective in preventing and treating people with coronavirus infection. Therefore, due to these previous multiple functions, colostrum is considered as a natural food, called miracle immune milk, and used as a medicine.

Timeline Kinetics of Systemic and Airway Immune Mediator Storm for Comprehensive Analysis of Disease Outcome in Critically Ill COVID-19 Patients.

In the present study, the levels of serum and airway soluble chemokines, pro-inflammatory/regulatory cytokines, and growth factors were quantified in critically ill COVID-19 patients (total n=286) at distinct time points (D0, D2-6, D7, D8-13 and D>14-36) upon Intensive Care Unit (ICU) admission. Augmented levels of soluble mediators were observed in serum from COVID-19 patients who progress to death. An opposite profile was observed in tracheal aspirate samples, indicating that systemic and airway microenvironment diverge in their inflammatory milieu. While a bimodal distribution was observed in the serum samples, a unimodal peak around D7 was found for most soluble mediators in tracheal aspirate samples. Systems biology tools further demonstrated that COVID-19 display distinct eccentric soluble mediator networks as compared to controls, with opposite profiles in serum and tracheal aspirates. Regardless the systemic-compartmentalized microenvironment, networks from patients progressing to death were linked to a pro-inflammatory/growth factor-rich, highly integrated center. Conversely, patients evolving to discharge exhibited networks of weak central architecture, with lower number of neighborhood connections and clusters of pro-inflammatory and regulatory cytokines. All in all, this investigation with robust sample size landed a comprehensive snapshot of the systemic and local divergencies composed of distinct immune responses driven by SARS-CoV-2 early on severe COVID-19.

Investigation of the mechanism of fangfeng tongsheng pills in the treatment COVID-19 by network pharmacology and molecular docking

Objective: To explore the active components and potential mechanism of Fangfeng Tongsheng Pills by using network pharmacology and molecular docking in the treatment of coronavirus disease 19(COVID-19). Methods The main chemical constituents and action targets of various medicines in Fangfeng Tongsheng Pills were collected via traditional Chinese medicine system pharmacology database and online analysis platform(TCMSP). The related targets of COVID-19 were collected by using GeneCards database, and the repeating parts with Fangfeng Tongsheng Pills were taken as the research targets. Cytoscape software was used to create a drug-target-disease network. The common target was imported into STRING database, and the protein-protein interaction network diagram was constructed by Cytoscape software. The GO(gene ontology) function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed by DAVID to predict their mechanism. The core components of Fangfeng Tongsheng Pills were docked with the therapeutic target of COVID-19 by AutoDock software. Results A total of 224 active compounds and 696 active targets were screened from Fangfeng Tongsheng Pills, including 79 targets coincided with COVID-19, and 10 active compounds, i.e. quercetin, luteolin, kaempferol,beta-sitosterol, naringenin, etc., 23 effective targets, i.e. PTGS2, PTGS1, NOS2, F10, DPP4, etc. A total of 65 GO function enrichment analysis results and 101 KEGG pathway enrichment results were obtained, including inflammatory response, tumor necrosis factor(TNF) signaling pathway, hypoxia inducible factor-1(HIF-1) signaling pathway, vascular endothelial growth factors(VEGF) signaling pathway, toll-like receptors(TLRs) signaling pathway, phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt) signaling pathway, and mitogen-activated protein kinase(MAPK) signaling pathway. Conclusion The active components in Fangfeng Tongsheng Pills, such as beta-sitosterol, quercetin, luteolin, kaempferol and naringenin, can combine with SARS-Co V2-3CL hydrolase and ACE2, act on the key target [TNF, Caspase-3, mitogen-activated protein kinase(MAPK1), interleukin-6(IL-6), prostaglandin-endoperoxide synthase 2(PGTS2)] of TNF, HIF-1, VEGF, MAPK and toll-like receptor signaling pathway, and play the roles of anti-inflammation, immune regulation, anti-hypoxic stress and anti-virus infection, thus play a role in the treatment of COVID-19.

New Achievements for the Treatment of Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) constitutes a heterogeneous group of malignancies that are often aggressive and associated with a poor prognosis. The development of new TNBC treatment strategies has become an urgent clinical need. Diagnosis and subtyping of TNBC are essential to establish alternative treatments and targeted therapies for every TNBC patient. Chemotherapy, particularly with anthracycline and taxanes, remains the backbone for medical management for both early and metastatic TNBC. More recently, immune checkpoint inhibitors and targeted therapy have revolutionized cancer treatment. Included in the different strategies studied for TNBC treatment is drug repurposing. Despite the numerous medications available, numerous studies in medicinal chemistry are still aimed at the synthesis of new compounds in order to find new antiproliferative agents capable of treating TNBC. Additionally, some supplemental micronutrients, nutraceuticals and functional foods can potentially reduce the risk of developing cancer or can retard the rate of growth and metastases of established malignant diseases. Finally, nanotechnology in medicine, termed nanomedicines, introduces nanoparticles of variable chemistry and architecture for cancer treatment. This review highlights the most recent studies in search of new therapies for the treatment of TNBC, along with nutraceuticals and repositioning of drugs.

SARS-CoV-2 infection- induced growth factors play differential roles in COVID-19 pathogenesis.

AIMS: Biologically active molecules cytokines and growth factors (GFs) are critical regulators of tissue injury/repair and emerge as key players in COVID-19 pathophysiology. However, specific disease stage of GFs dysregulation and, whether these GFs have associations with thromboembolism and tissue injury/repair in COVID-19 remain vague. MAIN METHODS: GF profiling in hospitalized moderate (non-ICU) and critically ill (ICU) COVID-19 patients was performed through legendPlex assay. KEY FINDINGS: Investigation revealed profound elevation of VEGF, PDGFs, EGF, TGF-α, FGF-basic, and erythropoietin (EPO) in moderate cases and decline or trend of decline with disease advancement. We found strong positive correlations of plasma VEGF, PDGFs, and EPO with endothelial dysfunction markers P-selectin and sCD40L. Interestingly, the HGF and G-CSF were upregulated at the moderate stage and remained elevated at the severe stage of COVID-19. Moreover, strong negative correlations of PDGFs (r2 = 0.238, P = 0.006), EPO (r2 = 0.18, P = 0.01) and EGF (r2 = 0.172, P = 0.02) and positive correlation of angiopoietin-2 (r2 = 0.267, P = 0.003) with D-dimer, a marker of thromboembolism, was observed. Further, plasma PDGFs (r2 = 0.199, P = 0.01), EPO (r2 = 0.115, P = 0.02), and EGF (r2 = 0.108, P = 0.07) exhibited negative correlations with tissue injury marker, myoglobin. SIGNIFICANCE: Taken together, unlike cytokines, most of the assessed GFs were upregulated at the moderate stage of COVID-19. The induction of GFs likely occurs due to endothelial dysfunction and may counter the adverse effects of cytokine storms which is reflected by inverse correlations of PDGFs, EPO, and EGF with thromboembolism and tissue injury markers. The findings suggest that the assessed GFs play differential roles in the pathogenesis of COVID-19.

Assessing the risk of pandemic outbreaks across municipalities with mathematical descriptors based on age and mobility restrictions.

By March 14th 2022, Spain is suffering the sixth wave of the COVID-19 pandemic. All the previous waves have been intimately related to the degree of imposed mobility restrictions and its consequent release. Certain factors explain the incidence of the virus across regions revealing the weak locations that probably require some medical reinforcements. The most relevant ones relate with mobility restrictions by age and administrative competence, i.e., spatial constrains. In this work, we aim to find a mathematical descriptor that could identify the critical communities that are more likely to suffer pandemic outbreaks and, at the same time, to estimate the impact of different mobility restrictions. We analyze the incidence of the virus in combination with mobility flows during the so-called second wave (roughly from August 1st to November 30th, 2020) using a SEIR compartmental model. After that, we derive a mathematical descriptor based on linear stability theory that quantifies the potential impact of becoming a hotspot. Once the model is validated, we consider different confinement scenarios and containment protocols aimed to control the virus spreading. The main findings from our simulations suggest that the confinement of the economically non-active individuals may result in a significant reduction of risk, whose effects are equivalent to the confinement of the total population. This study is conducted across the totality of municipalities in Spain.