Role of adjunctive treatment strategies in COVID-19 and a review of international and national clinical guidelines

Inflammation is a devastating outcome of cerebrovascular diseases (CVD), namely stroke and atherosclerosis. Numerous studies over the decade have shown that inflammasomes play a role in mediating inflammatory reactions post cellular injury occurring after a stroke or a rupture of an atherosclerotic plaque. In view of this, targeting these inflammatory pathways using different pharmacological therapies may improve outcomes in patients with CVD. Here, we review the mechanisms by which inflammasomes drive the pathogenesis of stroke and atherosclerosis. Also, discussed here are the possible treatment strategies available for inhibiting inflammasomes or their up-stream/down-stream mediators.

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Role of Flavonoids in Neurodegenerative Disorders with Special Emphasis on Tangeritin

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527318666190916141934 ◽

2019 ◽

Vol 18 (8) ◽

pp. 581-597 ◽

Cited By ~ 1

Author(s):

Ambreen Fatima ◽

Yasir Hasan Siddique

Keyword(s):

Medicinal Plants ◽

Mechanism Of Action ◽

Neurodegenerative Disorders ◽

Treatment Strategies ◽

Dietary Supplementation ◽

Plant Polyphenols ◽

Promising Candidate ◽

Naturally Occurring ◽

The Brain

Flavonoids are naturally occurring plant polyphenols found universally in all fruits, vegetables and medicinal plants. They have emerged as a promising candidate in the formulation of treatment strategies for various neurodegenerative disorders. The use of flavonoid rich plant extracts and food in dietary supplementation have shown favourable outcomes. The present review describes the types, properties and metabolism of flavonoids. Neuroprotective role of various flavonoids and the possible mechanism of action in the brain against the neurodegeneration have been described in detail with special emphasis on the tangeritin.

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Persistent Atrial Fibrillation: The Role of Left Atrial Posterior Wall Isolation and Ablation Strategies

Journal of Clinical Medicine ◽

10.3390/jcm10143129 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3129

Author(s):

Riyaz A. Kaba ◽

Aziz Momin ◽

John Camm

Keyword(s):

Atrial Fibrillation ◽

Left Atrial ◽

Pulmonary Veins ◽

Treatment Strategies ◽

Persistent Atrial Fibrillation ◽

Posterior Wall ◽

Cardiovascular Death ◽

Good Effect ◽

Complex Forms

Atrial fibrillation (AF) is a global disease with rapidly rising incidence and prevalence. It is associated with a higher risk of stroke, dementia, cognitive decline, sudden and cardiovascular death, heart failure and impairment in quality of life. The disease is a major burden on the healthcare system. Paroxysmal AF is typically managed with medications or endocardial catheter ablation to good effect. However, a large proportion of patients with AF have persistent or long-standing persistent AF, which are more complex forms of the condition and thus more difficult to treat. This is in part due to the progressive electro-anatomical changes that occur with AF persistence and the spread of arrhythmogenic triggers and substrates outside of the pulmonary veins. The posterior wall of the left atrium is a common site for these changes and has become a target of ablation strategies to treat these more resistant forms of AF. In this review, we discuss the role of the posterior left atrial wall in persistent and long-standing persistent AF, the limitations of current endocardial-focused treatment strategies, and future perspectives on hybrid epicardial–endocardial approaches to posterior wall isolation or ablation.

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Transient Receptor Potential C 1/4/5 Is a Determinant of MTI-101 Induced Calcium Influx and Cell Death in Multiple Myeloma

Cells ◽

10.3390/cells10061490 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1490

Author(s):

Osama M. Elzamzamy ◽

Brandon E. Johnson ◽

Wei-Chih Chen ◽

Gangqing Hu ◽

Reinhold Penner ◽

...

Keyword(s):

Multiple Myeloma ◽

Cell Death ◽

Transient Receptor Potential ◽

Cyclic Peptide ◽

Calcium Influx ◽

Acquired Resistance ◽

Treatment Strategies ◽

Prognostic Indicators ◽

Causative Role

Multiple myeloma (MM) is a currently incurable hematologic cancer. Patients that initially respond to therapeutic intervention eventually relapse with drug resistant disease. Thus, novel treatment strategies are critically needed to improve patient outcomes. Our group has developed a novel cyclic peptide referred to as MTI-101 for the treatment of MM. We previously reported that acquired resistance to HYD-1, the linear form of MTI-101, correlated with the repression of genes involved in store operated Ca2+ entry (SOCE): PLCβ, SERCA, ITPR3, and TRPC1 expression. In this study, we sought to determine the role of TRPC1 heteromers in mediating MTI-101 induced cationic flux. Our data indicate that, consistent with the activation of TRPC heteromers, MTI-101 treatment induced Ca2+ and Na+ influx. However, replacing extracellular Na+ with NMDG did not reduce MTI-101-induced cell death. In contrast, decreasing extracellular Ca2+ reduced both MTI-101-induced Ca2+ influx as well as cell death. The causative role of TRPC heteromers was established by suppressing STIM1, TRPC1, TRPC4, or TRPC5 function both pharmacologically and by siRNA, resulting in a reduction in MTI-101-induced Ca2+ influx. Mechanistically, MTI-101 treatment induces trafficking of TRPC1 to the membrane and co-immunoprecipitation studies indicate that MTI-101 treatment induces a TRPC1-STIM1 complex. Moreover, treatment with calpeptin inhibited MTI-101-induced Ca2+ influx and cell death, indicating a role of calpain in the mechanism of MTI-101-induced cytotoxicity. Finally, components of the SOCE pathway were found to be poor prognostic indicators among MM patients, suggesting that this pathway is attractive for the treatment of MM.

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Drug Resistance in Osteosarcoma: Emerging Biomarkers, Therapeutic Targets and Treatment Strategies

Cancers ◽

10.3390/cancers13122878 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2878

Author(s):

Claudia Maria Hattinger ◽

Maria Pia Patrizio ◽

Leonardo Fantoni ◽

Chiara Casotti ◽

Chiara Riganti ◽

...

Keyword(s):

Drug Resistance ◽

Therapeutic Targets ◽

Treatment Strategies ◽

Cure Rate ◽

Acquired Drug Resistance ◽

Unselected Patient ◽

Dismal Prognosis ◽

Non Coding Rnas ◽

High Grade Osteosarcoma

High-grade osteosarcoma (HGOS), the most common primary malignant tumor of bone, is a highly aggressive neoplasm with a cure rate of approximately 40–50% in unselected patient populations. The major clinical problems opposing the cure of HGOS are the presence of inherent or acquired drug resistance and the development of metastasis. Since the drugs used in first-line chemotherapy protocols for HGOS and clinical outcome have not significantly evolved in the past three decades, there is an urgent need for new therapeutic biomarkers and targeted treatment strategies, which may increase the currently available spectrum of cure modalities. Unresponsive or chemoresistant (refractory) HGOS patients usually encounter a dismal prognosis, mostly because therapeutic options and drugs effective for rescue treatments are scarce. Tailored treatments for different subgroups of HGOS patients stratified according to drug resistance-related biomarkers thus appear as an option that may improve this situation. This review explores drug resistance-related biomarkers, therapeutic targets and new candidate treatment strategies, which have emerged in HGOS. In addition to consolidated biomarkers, specific attention has been paid to the role of non-coding RNAs, tumor-derived extracellular vesicles, and cancer stem cells as contributors to drug resistance in HGOS, in order to highlight new candidate markers and therapeutic targets. The possible use of new non-conventional drugs to overcome the main mechanisms of drug resistance in HGOS are finally discussed.

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B Cells and Antibodies as Targets of Therapeutic Intervention in Neuromyelitis Optica Spectrum Disorders

Pharmaceuticals ◽

10.3390/ph14010037 ◽

2021 ◽

Vol 14 (1) ◽

pp. 37

Author(s):

Jan Traub ◽

Leila Husseini ◽

Martin S. Weber

Keyword(s):

B Cells ◽

Neuromyelitis Optica ◽

Plasma Cells ◽

Treatment Options ◽

Treatment Strategies ◽

Therapeutic Interventions ◽

Complement Factor ◽

Major Subset ◽

Spectrum Disorders

The first description of neuromyelitis optica by Eugène Devic and Fernand Gault dates back to the 19th century, but only the discovery of aquaporin-4 autoantibodies in a major subset of affected patients in 2004 led to a fundamentally revised disease concept: Neuromyelits optica spectrum disorders (NMOSD) are now considered autoantibody-mediated autoimmune diseases, bringing the pivotal pathogenetic role of B cells and plasma cells into focus. Not long ago, there was no approved medication for this deleterious disease and off-label therapies were the only treatment options for affected patients. Within the last years, there has been a tremendous development of novel therapies with diverse treatment strategies: immunosuppression, B cell depletion, complement factor antagonism and interleukin-6 receptor blockage were shown to be effective and promising therapeutic interventions. This has led to the long-expected official approval of eculizumab in 2019 and inebilizumab in 2020. In this article, we review current pathogenetic concepts in NMOSD with a focus on the role of B cells and autoantibodies as major contributors to the propagation of these diseases. Lastly, by highlighting promising experimental and future treatment options, we aim to round up the current state of knowledge on the therapeutic arsenal in NMOSD.

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The role of unconventional T cells in COVID-19

Irish Journal of Medical Science (1971 -) ◽

10.1007/s11845-021-02653-9 ◽

2021 ◽

Author(s):

Kristen Orumaa ◽

Margaret R. Dunne

Keyword(s):

Immune Response ◽

T Cells ◽

T Cell ◽

Treatment Strategies ◽

Γδ T Cells ◽

Protective Role ◽

T Cell Subsets ◽

Viral Immunity ◽

Mait Cells

AbstractCOVID-19 is a respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first documented in late 2019, but within months, a worldwide pandemic was declared due to the easily transmissible nature of the virus. Research to date on the immune response to SARS-CoV-2 has focused largely on conventional B and T lymphocytes. This review examines the emerging role of unconventional T cell subsets, including γδ T cells, invariant natural killer T (iNKT) cells and mucosal associated invariant T (MAIT) cells in human SARS-CoV-2 infection.Some of these T cell subsets have been shown to play protective roles in anti-viral immunity by suppressing viral replication and opsonising virions of SARS-CoV. Here, we explore whether unconventional T cells play a protective role in SARS-CoV-2 infection as well. Unconventional T cells are already under investigation as cell-based immunotherapies for cancer. We discuss the potential use of these cells as therapeutic agents in the COVID-19 setting. Due to the rapidly evolving situation presented by COVID-19, there is an urgent need to understand the pathogenesis of this disease and the mechanisms underlying its immune response. Through this, we may be able to better help those with severe cases and lower the mortality rate by devising more effective vaccines and novel treatment strategies.

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Silencing of MEG3 attenuated the role of lipopolysaccharides by modulating the miR-93-5p/PTEN pathway in Leydig cells

Reproductive Biology and Endocrinology ◽

10.1186/s12958-021-00712-5 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Xu Zhou ◽

Jingliang He ◽

Jinbo Chen ◽

Yu Cui ◽

Zhenyu Ou ◽

...

Keyword(s):

Cell Viability ◽

Cell Apoptosis ◽

Leydig Cells ◽

Treatment Strategies ◽

Pten Expression ◽

Luciferase Reporter ◽

Western Blots ◽

New Treatment ◽

Lps Treatment

Abstract Background Leydig cells reflect the activation of inflammation, decrease of androgen production, inhibition of cell growth and promotion of cell apoptosis under orchitis. Maternally expressed gene 3 (MEG3) exerts a crucial role in various human diseases, but under orchitis, the role and underlying molecular mechanism of MEG3 in Leydig cells remain unclear. Methods Lipofectamine 2000 was used for the cell transfections. qPCR and western blots assay were applied to assess the gene expression. ELISA assay was used to measure the TNFα, IL6 and testosterone secretion. CCK8 and EdU assay was employ to test the cell viability and proliferation respectively. Luciferase reporter and RIP assay were introduced to detect the binding of miR-93-5p with MEG3 and PTEN. Results Lipopolysaccharides (LPS) induced TNFα and IL6 secretion, lowered testosterone production, inhibited cell viability and proliferation, and induced cell apoptosis in Leydig cells. MEG3 was upregulated in Leydig cells treated with LPS and that knockdown of MEG3 inhibited the role of LPS in Leydig cells. MEG3 absorbed miR-93-5p and that suppression of miR-93-5p restored the role of silenced MEG3 in Leydig cells under LPS treatment. miR-93-5p inhibited PTEN expression and that over-expressed PTEN alleviated the effect of miR-93-5p in Leydig cells treated with LPS. LPS activated the MEG3/miR-93-5p/PTEN signalling pathway in Leydig cells. Conclusions This study revealed that MEG3 serves as a molecular sponge to absorb miR-93-5p, thus leading to elevation of PTEN expression in Leydig cells under LPS treatment, offering a theoretical basis on which to establish potential new treatment strategies for orchitis.

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The Potential Association between the Risk of Post-Surgical Adhesion and the Activated Local Angiotensin II Type 1 Receptors: Need for Novel Treatment Strategies

Gastrointestinal Tumors ◽

10.1159/000514614 ◽

2021 ◽

pp. 1-8

Author(s):

Mahmood Tavakkoli ◽

Saeed Aali ◽

Borzoo Khaledifar ◽

Gordon A. Ferns ◽

Majid Khazaei ◽

...

Keyword(s):

Angiotensin Ii ◽

Molecular Mechanisms ◽

Transforming Growth Factor ◽

Therapeutic Potential ◽

Angiotensin Receptor Blockers ◽

Surgical Techniques ◽

Treatment Strategies ◽

Transforming Growth Factor Β

Background: Post-surgical adhesion bands (PSABs) are a common complication after abdominal or pelvic surgeries for different reasons like cancer treatment. Despite improvements in surgical techniques and the administration of drugs or the use of physical barriers, there has only been limited improvement in the frequency of postoperative adhesions. Complications of PSAB are pain, infertility, intestinal obstruction, and increased mortality. The most important molecular mechanisms for the development of PSAB are inflammatory response, oxidative stress, and overexpression of pro-fibrotic molecules such as transforming growth factor β. However, questions remain about the pathogenesis of this problem, for example, the causes for individual differences or why certain tissue sites are more prone to post-surgical adhesions. Summary: Addressing the pathological causes of PSAB, the potential role of local angiotensin II/angiotensin II type 1 receptors (AngII/AT1R), may help to prevent this problem. Key Message: The objective of this article was to explore the role of the AngII/AT1R axis potential to induce PSAB and the therapeutic potential of angiotensin receptor blockers in the prevention and treatment of PSAB.

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The Phosphoarginine Phosphatase PtpB from Staphylococcus aureus Is Involved in Bacterial Stress Adaptation during Infection

Cells ◽

10.3390/cells10030645 ◽

2021 ◽

Vol 10 (3) ◽

pp. 645

Author(s):

Mohamed Ibrahem Elhawy ◽

Sylvaine Huc-Brandt ◽

Linda Pätzold ◽

Laila Gannoun-Zaki ◽

Ahmed Mohamed Mostafa Abdrabou ◽

...

Keyword(s):

Oxidative Stress ◽

Staphylococcus Aureus ◽

Treatment Strategies ◽

Physiological Role ◽

Aureus Strain ◽

Stress Adaptation ◽

Cellular Mechanisms ◽

Host Interaction ◽

Liver And Kidney

Staphylococcus aureus continues to be a public health threat, especially in hospital settings. Studies aimed at deciphering the molecular and cellular mechanisms that underlie pathogenesis, host adaptation, and virulence are required to develop effective treatment strategies. Numerous host-pathogen interactions were found to be dependent on phosphatases-mediated regulation. This study focused on the analysis of the role of the low-molecular weight phosphatase PtpB, in particular, during infection. Deletion of ptpB in S. aureus strain SA564 significantly reduced the capacity of the mutant to withstand intracellular killing by THP-1 macrophages. When injected into normoglycemic C57BL/6 mice, the SA564 ΔptpB mutant displayed markedly reduced bacterial loads in liver and kidney tissues in a murine S. aureus abscess model when compared to the wild type. We also observed that PtpB phosphatase-activity was sensitive to oxidative stress. Our quantitative transcript analyses revealed that PtpB affects the transcription of various genes involved in oxidative stress adaptation and infectivity. Thus, this study disclosed first insights into the physiological role of PtpB during host interaction allowing us to link phosphatase-dependent regulation to oxidative bacterial stress adaptation during infection.

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