The opportunity for massage therapy development for relieving long COVID symptoms: a literature review

The COVID-19 pandemic situation affected population health and lifestyle not only for a short period but also long period. Long COVID symptoms is a long-term illness after COVID condition. Long COVID symptoms greatly affected to quality of life of patients. Massage is a unique treatment form of alternative medicine that can promote health in various dimensions. From the previous studies, massage has affected to Long COVID mechanism via anti-inflammatory process, immune system enhancing process, and hormone level balancing that related to Long COVID symptoms as well as being able to reduce the symptoms of the long COVID symptoms. The study about the efficacy and safety of massage against Long COVID symptoms is the essential approach to increase the value of massage and develop health services in the future.

Immunostimulatory and anti­obesity activities of Adenocaulon himalaicum leaves in RAW264.7 and 3T3­L1 cells.

The present study investigated the immunostimulatory activity and anti-obesity activity of Adenocaulon himalaicum leaf extracts (AHL) in RAW264.7 cells and 3T3-L1 cells. AHL increased the production of immunostimulatory factors, such as NO, inducible nitric oxide synthase (iNOS), IL-1ß, IL-6 and TNF-α and activated the phagocytotic activity in RAW264.7 cells. Inhibition of Toll-like receptor 4 (TLR4) attenuated the AHL-mediated production of immunostimulatory factors and activation of phagocytic activity in RAW264.7 cells. Inhibition of p38 and JNK blocked the AHL-mediated production of immunostimulatory factors, whereas inhibition of TLR4 suppressed the AHL-mediated phosphorylation of p38 and JNK. Additionally, AHL blocked the lipid accumulation in 3T3-L1 cells. AHL downregulated proliferator-activated receptor γ, CCAAT enhancer binding protein α and perilipin-1 levels, while upregulating adipose triglyceride lipase, phosphorylated (p-)hormone-sensitive lipase, p-adenosine monophosphate activated protein kinase, uncoupling protein 1, peroxisome-proliferator-activated receptor-γ coactivator-1 α and PR domain containing 16 levels in 3T3-L1 cells. These findings suggested that AHL may exert immunostimulatory activity through macrophages via TLR4-mediated activation of p38 and JNK and anti-obesity activity by blocking lipid accumulation via the inhibition of adipogenesis and induction of lipolysis and browning of white adipocytes.

A review of the medicinal plants with immune-boosting potential

Background: Humanity is faced with various kinds of infections (viral, bacterial and fungal). The recent spread of coronavirus disease 2019 (COVID-19) has led the World Health Organization to declare the coronavirus disease outbreak as a global pandemic. Medical experts suggested that people with high immunity tend to survive the infection more than those with low immunity. Hence, people must boost their immunity by consuming more fruit and vegetable or medications with immune-boosting potential to survive any form of unforeseen infections. Aim: This study aimed to review horticultural fruit, vegetables and medicinal plants with immune-boosting potentials that may be useful in drug formulations to combat infectious diseases. Methods: A literature search was conducted on electronic databases such as Google Scholar, Scopus and Web of Science. Several terms and free text words were combined in an appropriate manner to perform the search. Identified articles were reviewed independently for eligibility and extract of information. Results: The study highlighted medicinal and horticultural crops with the potential to combat the symptoms of Covid-19 such as cold, cough, chest pain and high fever. Details about how despite effective vaccines, respiratory infections such as asthma, tuberculosis, pneumonia and measles are causing significant death worldwide. Conclusion: This review highlights the fact that pharmaceutical companies should be encouraged to maximise the use of medicinal plants suggested for drug formulation strategies and humans should consume more fruit and vegetables to boost their immune systems. Contribution: The use of natural products is now receiving global attention against synthetic ones to combat infections and the recent COVID-19 outbreak has called for innovative methods of treating the disease and its symptoms. This review provided information about medicinal plants with immune-boosting potential that when consumed or used in drug formulations can boost immune systems against various forms of infections. Insights on how the burden of diseases can be reduced and healthy lifestyles enhanced naturally are provided for social and economic developments. © 2022. The Authors.

Saponins: Research Progress and Their Potential Role in the Post-COVID-19 Pandemic Era.

In the post-COVID-19 pandemic era, the new global situation and the limited therapeutic management of the disease make it necessary to take urgent measures in more effective therapies and drug development in order to counteract the negative global impacts caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its new infectious variants. In this context, plant-derived saponins-glycoside-type compounds constituted from a triterpene or steroidal aglycone and one or more sugar residues-may offer fewer side effects and promising beneficial pharmacological activities. This can then be used for the development of potential therapeutic agents against COVID-19, either as a therapy or as a complement to conventional pharmacological strategies for the treatment of the disease and its prevention. The main objective of this review was to examine the primary and current evidence in regard to the therapeutic potential of plant-derived saponins against the COVID-19 disease. Further, the aim was to also focus on those studies that highlight the potential use of saponins as a treatment against SARS-CoV-2. Saponins are antiviral agents that inhibit different pharmacological targets of the virus, as well as exhibit anti-inflammatory and antithrombotic activity in relieving symptoms and clinical complications related to the disease. In addition, saponins also possess immunostimulatory effects, which improve the efficacy and safety of vaccines for prolonging immunogenicity against SARS-CoV-2 and its infectious variants.

Messenger RNA Therapeutics: Start of a New Era in Medicine

Last decade has witnessed tremendous growth in the new promising treatment options based on mRNA, RNAi, antisense RNA, and RNA aptamers, the four classes of RNA-based therapeutics. Among these, mRNA-based therapy is centered on producing proteins within the cells to supplant deficient or abnormal proteins and in vaccination to a target pathogen. The potential of mRNA therapeutics is evident from the two major mRNA vaccines approved for COVID-19: developed by Moderna and by Pfizer. Nonetheless, mRNA therapeutic potential extends far beyond this, such as in treating genetic diseases, cancers, and other infectious diseases. Given the potential of mRNA therapeutics, this chapter is written to provide the reader an insight into the features of several synthetic mRNA platforms, production, purification;strategies to increase the stability and reduce the immunogenicity of therapeutic mRNA molecules;delivery methods of these mRNAs in vivo;and their applications, safety, and efficacy. Graphical : A detailed diagram of the chemically modified mRNA, with the in vitro delivery modes on the left, and the myriad of applications, namely the treatment of major genetic diseases on the right. The IVT mRNA is represented with more details above the diagram. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Self-assembling short immunostimulatory duplex RNAs with broad-spectrum antiviral activity.

The current coronavirus disease 2019 (COVID-19) pandemic highlights the need for broad-spectrum antiviral therapeutics. Here we describe a new class of self-assembling immunostimulatory short duplex RNAs that potently induce production of type I and type III interferon (IFN-I and IFN-III). These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique sequence motif (sense strand, 5'-C; antisense strand, 3'-GGG) that mediates end-to-end dimer self-assembly. The presence of terminal hydroxyl or monophosphate groups, blunt or overhanging ends, or terminal RNA or DNA bases did not affect their ability to induce IFN. Unlike previously described immunostimulatory small interfering RNAs (siRNAs), their activity is independent of Toll-like receptor (TLR) 7/8, but requires the RIG-I/IRF3 pathway that induces a more restricted antiviral response with a lower proinflammatory signature compared with immunostimulant poly(I:C). Immune stimulation mediated by these duplex RNAs results in broad-spectrum inhibition of infections by many respiratory viruses with pandemic potential, including severe acute respiratory syndrome coronavirus (SARS-CoV)-2, SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus (HCoV)-NL63, and influenza A virus in cell lines, human lung chips that mimic organ-level lung pathophysiology, and a mouse SARS-CoV-2 infection model. These short double-stranded RNAs (dsRNAs) can be manufactured easily, and thus potentially could be harnessed to produce broad-spectrum antiviral therapeutics.

Fighting HIV-1 Persistence: At the Crossroads of "Shoc-K and B-Lock".

Despite the success of highly active antiretroviral therapy (HAART), integrated HIV-1 proviral DNA cannot be eradicated from an infected individual. HAART is not able to eliminate latently infected cells that remain invisible to the immune system. Viral sanctuaries in specific tissues and immune-privileged sites may cause residual viral replication that contributes to HIV-1 persistence. The "Shock or Kick, and Kill" approach uses latency reversing agents (LRAs) in the presence of HAART, followed by cell-killing due to viral cytopathic effects and immune-mediated clearance. Different LRAs may be required for the in vivo reactivation of HIV-1 in different CD4+ T cell reservoirs, leading to the activation of cellular transcription factors acting on the integrated proviral HIV-1 LTR. An important requirement for LRA drugs is the reactivation of viral transcription and replication without causing a generalized immune activation. Toll-like receptors, RIG-I like receptors, and STING agonists have emerged recently as a new class of LRAs that augment selective apoptosis in reactivated T lymphocytes. The challenge is to extend in vitro observations to HIV-1 positive patients. Further studies are also needed to overcome the mechanisms that protect latently infected cells from reactivation and/or elimination by the immune system. The Block and Lock alternative strategy aims at using latency promoting/inducing agents (LPAs/LIAs) to block the ability of latent proviruses to reactivate transcription in order to achieve a long term lock down of potential residual virus replication. The Shock and Kill and the Block and Lock approaches may not be only alternative to each other, but, if combined together (one after the other), or given all at once [namely "Shoc-K(kill) and B(block)-Lock"], they may represent a better approach to a functional cure.

PASylated Thymosin α1: A Long-Acting Immunostimulatory Peptide for Applications in Oncology and Virology.

Thymosin α1 (Tα1) is an immunostimulatory peptide for the treatment of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and used as an immune enhancer, which also offers prospects in the context of COVID-19 infections and cancer. Manufacturing of this N-terminally acetylated 28-residue peptide is demanding, and its short plasma half-life limits in vivo efficacy and requires frequent dosing. Here, we combined the PASylation technology with enzymatic in situ N-acetylation by RimJ to produce a long-acting version of Tα1 in Escherichia coli at high yield. ESI-MS analysis of the purified fusion protein indicated the expected composition without any signs of proteolysis. SEC analysis revealed a 10-fold expanded hydrodynamic volume resulting from the fusion with a conformationally disordered Pro/Ala/Ser (PAS) polypeptide of 600 residues. This size effect led to a plasma half-life in rats extended by more than a factor 8 compared to the original synthetic peptide due to retarded kidney filtration. Our study provides the basis for therapeutic development of a next generation thymosin α1 with prolonged circulation. Generally, the strategy of producing an N-terminally protected PASylated peptide solves three major problems of peptide drugs: (i) instability in the expression host, (ii) rapid degradation by serum exopeptidases, and (iii) low bioactivity because of fast renal clearance.