Exhaustion and over-activation of immune cells in COVID-19: challenges and therapeutic opportunities

Exhaustion of immune cells in COVID-19 remains a serious concern for infection management and therapeutic interventions. As reported, immune cells such as T effector cells (Teff), T regulatory cells (Tregs), natural killer cells (NKs), and antigen-presenting cells (APCs) exhibit uncontrolled functions in COVID-19. Unfortunately, the mechanisms that orchestrate immune cell functionality and virus interaction are still unknown. Recent studies linked adaptive immune cell exhaustion to underlying epigenetic mechanisms that regulate the epigenetic transcription of inhibitory immune checkpoint receptors (ICs). Further to that, the over-activation of T cells accompanied by the dysfunctionality of DCs and Tregs may enhance uncontrollable alveoli inflammation and cytokine storm in COVID-19. This might explain the reasons behind the failure of DC-based vaccines in inducing sufficient anti-viral responses. This review explains the processes behind the over-activation and exhaustion of innate and adaptive immune cells in COVID-19, which may contribute to developing novel immune intervention strategies

Promising use of immune cell‐derived exosomes in the treatment of SARS‐CoV‐2 infections

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is persistently threatening the lives of thousands of individuals globally. It triggers pulmonary oedema, driving to dyspnoea and lung failure. Viral infectivity of coronavirus disease 2019 (COVID‐19) is a genuine challenge due to the mutagenic genome and mysterious immune‐pathophysiology. Early reports highlighted that extracellular vesicles (exosomes, Exos) work to enhance COVID‐19 progression by mediating viral transmission, replication and mutations. Furthermore, recent studies revealed that Exos derived from immune cells play an essential role in the promotion of immune cell exhaustion by transferring regulatory lncRNAs and miRNAs from exhausted cells to the active cells. Fortunately, there are great chances to modulate the immune functions of Exos towards a sustained repression of COVID‐19. Engineered Exos hold promising immunotherapeutic opportunities for remodelling cytotoxic T cells’ function. Immune cell‐derived Exos may trigger a stable epigenetic repression of viral infectivity, restore functional cytokine‐producing T cells and rebalance immune response in severe infections by inducing functional T regulatory cells (Tregs). This review introduces a view on the current outcomes of immunopathology, and immunotherapeutic applications of immune cell‐derived Exos in COVID‐19, besides new perspectives to develop novel patterns of engineered Exos triggering novel anti‐SARS‐CoV‐2 immune responses

NORMAL VASCULAR REACTIVITY IS RESTORED BY APIGENIN IN DIABETIC RATS

Objective: Diabetes is a disease whose complications have serious implications for the health of sufferers; one of the most serious such complications is the deterioration of vascular reactivity. Apigenin is a natural flavonoid with PKC inhibiting and antioxidant properties. In this study, the impact of apigenin on vascular reactivity deterioration was investigated.Methods: Insulin resistance (IR) and insulin deficiency (ID) were induced by fructose and streptozotocin respectively. The isolated aortae vasoconstriction response to phenylephrine (PE) and potassium chloride (KCl) in addition to the vasodilation response to acetylcholine (ACh) and sodium nitroprusside (SNP) were tested.Results: IR and ID were associated with significantly exaggerated vasoconstriction to KCl and PE while significantly impaired vasodilation to ACh. Response to SNP was not significantly affected by both IR and ID. In vitro incubation with apigenin (7 7µM) for 20 min restored normal responses to PE, KCl and ACh in aortae isolated from insulin-resistant or insulin-deficient rats. Incubation for one hour with the PKC stimulant, phorbol 12-myristate 13-acetate (PMA, 800 nM) resulted in aortic impairment similar to that seen in aortae isolated from IR and ID animals. Incubation with both apigenin prevented PMA-induced exaggerated vasoconstriction response to both PE and KCl.Conclusion: Apigenin alleviates vascular exaggerated vasoconstriction and impaired dilation associated with diabetes or PKC activated

Relationship between Vitamin D Deficiency and Respiratory Infection in Intensive Care Unit Patients

Objectives: the current study aims to investigate the correlation between vitamin D deficiency and respiratory tract (URT) infection in hospitalized patients. Subjects and methods: a cross sectional observational study was conducted among patients with URT infections admitted to the intensive care unit (ICU). Results: From 30 ICU respiratory infected patients who were included in the study, results showed that all patients’ serum vitamin D levels were below normal, where 3.3% of patients showed a relative insufficiency and 96.7% represent deficiency. This study included 16 females and 14 males. The results showed that deficiency in females appears to be more than in males with a mean of 15.42 nmol/L and 16.nmo/L respectively. Variable readings of serum vit. D level appeared with the various microorganisms. The lowest level of the vitamin was found with Acinetobacter baumannii, Pseudomonas aeruginosa and Ataphylococcus aureus respectively. In addition, the present study showed that the level of WBCS is inversely proportional to the level of vit. D in most patients. Moreover, patients who were on combination therapy of antibiotic and corticosteroid showed lowest mean of serum vit. D level than patients who were on antibiotic or corticosteroid alone. Conclusion: the present study showed that all patients with respiratory tract infection in ICU have either vit D insufficiency or deficiency. Moreover, there was an inverse relationship between vit D and WBCs level. This may be attributed to the role of vit D in immunity, so vit D may be recommended to be prescribed to avoid further deficiency and to boost the immunity in patient with respiratory tract infection

Cytotoxic and Antimicrobial Compounds from the Marine-Derived Fungus, Penicillium Species

The organic extract of liquid cultures of the marine-derived Penicillium sp. was investigated. Fractionation of the extracts of the fungus led to the purification and identification of two new compounds, penicillatides A (1) and B (2), together with the previously reported cyclo(R-Pro–S-Phe) (3) and cyclo(R-Pro–R-Phe) (4). The structures of compounds 1–4 were assigned by extensive interpretation of their NMR and high-resolution mass spectrometry (HRMS). The antiproliferative and cytotoxic activities of the compounds against three human cancer cell lines as well as their antimicrobial activity against several pathogens were evaluated. Compounds 2–4 displayed variable cytotoxic and antimicrobial activities

The Effect of Ownership Structure on Company Performance: Evidence From Emerging Market

This paper uses panel data to examine the impact of ownership structure index on the financial performance of 73 listed companies of the Indian national stock exchange from 2009 to 2016. To measure the Panel Regression in this study, the FEM model was used. The different dimensions of the ownership structure index involve ten items used as the Independent variable of this study. Two measures have been adopted to estimate the firm performance that is; ROA and ROE. In contrast, the control variables are firm size and leverage. This study's empirical evidence shows that the ownership structure index has significant impact on a firm's performance measured by ROA and ROE of Indian Nifty 100 listed companies. Findings of this study support previous empirical studies performed and add some value in the research area of finance that explores different aspects of the board of directors' index and ownership structure index in Indian market by using Nifty 100 as an example