Sub-Acute Toxicity Study of Pegagan Embun (Hydrocotyle Sibthorpioides Lam.) Extract on the Sgpt and Sgot Level of Wistar White Male Rats

Objective: Pegagan embun (Hydrocotyle sibthorpioides Lam.) is one of the herbs used in ethnomedicines as an immunostimulant during the COVID-19 pandemic. This present study aims to discover the potential toxicity effect of pegagan embun extract through sub-acute administration on the SGPT and SGOT levels of Wistar white male rats. Method(s): Thirty-six test animals were divided into four groups: the control group was given Na CMC 0.5%, and the treatment groups were treated with ethanol extract of pegagan embun at doses of 7, 35, and 150 mg/kgBW. All groups were treated orally for 7, 14, and 21 d once daily. On the 8th, 15th, and 22nd day, the SGPT and SGOT of the test animal level were measured. The data were analyzed by two-way ANOVA followed by Duncan's multiple range test (p<0.05). Result(s): The study revealed that administration of pegagan embun extract did not cause any harmful effect on the liver but significantly decreased the level of SGPT and SGOT influenced by the variety of doses and duration of administration (p<0.05). Significant reductions in SGPT and SGOT levels are seen after extract administration at dosages of 7 mg/kgBW for 21 d. Conclusion(s): This study showed that pegagan embun (Hydrocotyle sibthorpioides Lam.) extract sub-acute administration at doses of 7, 35, and 150 mg/kgBW is relatively non-toxic and safe to be used as an immunostimulant. There was no sign of damage showed in the liver of treated rats based on the levels of SGOT and SGPT.Copyright © 2023 The Authors. Published by Innovare Academic Sciences Pvt Ltd.

Investigation on the Essential Oils of the Achillea Species: From Chemical Analysis to the In Silico Uptake against SARS-CoV-2 Main Protease.

In this study, phytochemicals extracted from three different Achillea genera were identified and analyzed to be screened for their interactions with the SARS-CoV-2 main protease. In particular, the antiviral potential of these natural products against the SARS-CoV-2 main protease was investigated, as was their effectiveness against the SARS-CoV-1 main protease as a standard (due to its high similarity with SARS-CoV-2). These enzymes play key roles in the proliferation of viral strains in the human cytological domain. GC-MS analysis was used to identify the essential oils of the Achillea species. Chemi-informatics tools, such as AutoDock 4.2.6, SwissADME, ProTox-II, and LigPlot, were used to investigate the action of the pharmacoactive compounds against the main proteases of SARS-CoV-1 and SARS-CoV-2. Based on the binding energies of kessanyl acetate, chavibetol (m-eugenol), farnesol, and 7-epi-ß-eudesmol were localized at the active site of the coronaviruses. Furthermore, these molecules, through hydrogen bonding with the amino acid residues of the active sites of viral proteins, were found to block the progression of SARS-CoV-2. Screening and computer analysis provided us with the opportunity to consider these molecules for further preclinical studies. Furthermore, considering their low toxicity, the data may pave the way for new in vitro and in vivo research on these natural inhibitors of the main SARS-CoV-2 protease.

Local Case to Global Phenomenon: The Vanishing of Elisa Lam in the Digital Streaming Era

The viral video is an extremely well-known concept in the present era, especially fueled by the COVID-19 pandemic. A great example of this phenomenon is the video of Elisa Lam, a Canadian student, who vanished mysteriously at the Cecil Hotel in Los Angeles during her vacation to California in the United States of America on January 31, 2013. The video of Elisa Lam became viral after the Los Angeles Police Department (LAPD) released the only video surveillance of her in the elevator of the Cecil Hotel on February 15, 2013, via its website. The reason for releasing the video by the LAPD was that they had difficulty finding Lam, and there was not enough evidence thus;they hoped that the public would help solve the case. After its release, the eerie video became viral as digital content creators and conspiracy theorists started sharing the video on multiple social media platforms. The primary platform, which supported and accelerated the viral spreading of the video, was YouTube. One of the first YouTubers who encountered the video on the LAPD website while looking for popular content that would grab people’s attention was John Lordan, the owner of the YouTube account LordanARTs. Lordan, among other YouTubers, started sharing the Lam video and began a discussion dissecting the many unusual aspects of the video, including Lam’s behavior, gestures, and environment. Following this, what started as a local missing person investigation became a global phenomenon. The viral video prompted the production of the Netflix documentary called Crime Scene: The Vanishing at the Cecil Hotel (2021), exploring the Elisa Lam case, the notorious Cecil Hotel, and its violent unnerving history. As Netflix became one of the most popular subscription videoon-demand services (SVODs) in the era of the COVID-19 pandemic, the release of the documentary re-fired the popularity of this case and the Elisa Lam video even after eight years. This ongoing popularity is showcased by the view count of the Elisa Lam video uploaded by the YouTuber Dennis Romero, which has over 30 million views at the moment since its first release date of February 13, 2013. The purpose of this chapter is to examine how local news can become viral, therefore;global, especially fueled by the increase of digital content and while being spread by various platforms. This study investigates the concepts of media convergence, participatory culture, collective intelligence, and how various accounts on various digital platforms approached this case, making the video a global phenomenon. In addition, the public’s behavior on social media, shaped and influenced by each other, and how this behavior may transform into cyberbullying while impacting innocent bystanders’ lives are analyzed. © Peter Lang GmbH Internationaler Verlag der Wissenschaften Berlin 2022. All rights reserved.

The Primacy of Moringa (Moringa oleiferaLam.) in Boosting Nutrition Statusand Immunity Defence Amidst the COVID-19 Catastrophe: A Perspective br

A severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led novel coronavirus disease (COVID-19)outbreak spread through China has become the biggest global public health challenge today. The virus upon sev-eral mutations has led to the resurgence of more infectious and lethal variants infecting over 298 million peoplewith more than 5.46 million deaths worldwide by the end of December, 2021. Though vaccines are available, var-ious preventive measures particularly a high body immunity is still extremely important which determines thelikelihood of disease severity and subsequent recovery in the current and future pandemics. This review acknowl-edges the potentiality of miraculousMoringa oleiferaLam. against recently evolved novel coronavirus and accom-panying health complications. Moringa a well-proven super-food, densely packed with an abundant quantity of92 minerals, several vitamins, 46 antioxidants, and numerous bioactive compounds, thus own a massive thera-peutic potential for healing all levels of nutritional deficiencies and poor immunities and cure above 300 diseases.Moringa acts as anti-asthmatic, anti-cancerous, anti-diabetic, anti-inflammatory, hypotensive, hepatic, renal andcardio-protective, and anti-viral in nature. Thus it may reduce the severity of COVID-19 infections and associatedserious medical emergencies. In addition, self-isolation at home or the workplace has put people at increased riskof physical and mental sicknesses, which could be simply addressed by integrating this wonderful plant intoeveryday diet. Furthermore, the immune-modulatory properties and viral inhibiting nature of moringa contributeto reduced risk of COVID-19 infection and quicker recovery from its symptoms. As per the existing pieces of literature, it is a great time to harness the esteemed moringa for safeguarding people from the terrible ongoingCOVID-19 situation and other future pandemics

Towards Accurate Point-of-Care Tests for Tuberculosis in Children.

In childhood tuberculosis (TB), with an estimated 69% of missed cases in children under 5 years of age, the case detection gap is larger than in other age groups, mainly due to its paucibacillary nature and children's difficulties in delivering sputum specimens. Accurate and accessible point-of-care tests (POCTs) are needed to detect TB disease in children and, in turn, reduce TB-related morbidity and mortality in this vulnerable population. In recent years, several POCTs for TB have been developed. These include new tools to improve the detection of TB in respiratory and gastric samples, such as molecular detection of Mycobacterium tuberculosis using loop-mediated isothermal amplification (LAMP) and portable polymerase chain reaction (PCR)-based GeneXpert. In addition, the urine-based detection of lipoarabinomannan (LAM), as well as imaging modalities through point-of-care ultrasonography (POCUS), are currently the POCTs in use. Further to this, artificial intelligence-based interpretation of ultrasound imaging and radiography is now integrated into computer-aided detection products. In the future, portable radiography may become more widely available, and robotics-supported ultrasound imaging is currently being trialed. Finally, novel blood-based tests evaluating the immune response using "omic-"techniques are underway. This approach, including transcriptomics, metabolomic, proteomics, lipidomics and genomics, is still distant from being translated into POCT formats, but the digital development may rapidly enhance innovation in this field. Despite these significant advances, TB-POCT development and implementation remains challenged by the lack of standard ways to access non-sputum-based samples, the need to differentiate TB infection from disease and to gain acceptance for novel testing strategies specific to the conditions and settings of use.

Angiotensin-Converting Enzyme 2 (ACE2), Transmembrane Peptidase Serine 2 (TMPRSS2), and Furin Expression Increases in the Lungs of Patients with Idiopathic Pulmonary Fibrosis (IPF) and Lymphangioleiomyomatosis (LAM): Implications for SARS-CoV-2 (COVID-19) Infections.

We previously reported higher ACE2 levels in smokers and patients with COPD. The current study investigates if patients with interstitial lung diseases (ILDs) such as IPF and LAM have elevated ACE2, TMPRSS2, and Furin levels, increasing their risk for SARS-CoV-2 infection and development of COVID-19. Surgically resected lung tissue from IPF, LAM patients, and healthy controls (HC) was immunostained for ACE2, TMPRSS2, and Furin. Percentage ACE2, TMPRSS2, and Furin expression was measured in small airway epithelium (SAE) and alveolar areas using computer-assisted Image-Pro Plus 7.0 software. IPF and LAM tissue was also immunostained for myofibroblast marker α-smooth muscle actin (α-SMA) and growth factor transforming growth factor beta1 (TGF-ß1). Compared to HC, ACE2, TMPRSS2 and Furin expression were significantly upregulated in the SAE of IPF (p < 0.01) and LAM (p < 0.001) patients, and in the alveolar areas of IPF (p < 0.001) and LAM (p < 0.01). There was a significant positive correlation between smoking history and ACE2 expression in the IPF cohort for SAE (r = 0.812, p < 0.05) and alveolar areas (r = 0.941, p < 0.01). This, to our knowledge, is the first study to compare ACE2, TMPRSS2, and Furin expression in patients with IPF and LAM compared to HC. Descriptive images show that α-SMA and TGF-ß1 increase in the IPF and LAM tissue. Our data suggests that patients with ILDs are at a higher risk of developing severe COVID-19 infection and post-COVID-19 interstitial pulmonary fibrosis. Growth factors secreted by the myofibroblasts, and surrounding tissue could further affect COVID-19 adhesion proteins/cofactors and post-COVID-19 interstitial pulmonary fibrosis. Smoking seems to be the major driving factor in patients with IPF.

COVID-19 in a patient with sporadic lymphangioleiomyomatosis awaiting lung transplantation.

Coronavirus disease 2019 (COVID-19) is an emerging viral disease with a mortality that depends on the individual's condition. Underlying comorbidities are major risk factors for COVID-19-related morbidity and mortality. However, information regarding the clinical course of COVID-19 in patients with rare respiratory system diseases is lacking. Here, we present a case of severe COVID-19 in a patient with advanced sporadic lymphangioleiomyomatosis (LAM) who was awaiting lung transplantation. She experienced a marked worsening of her respiratory status despite the limited size of the infiltrations seen on chest computed tomography. She responded to treatment with dexamethasone and remdesivir, and did not require mechanical ventilation. She recovered her pre-COVID-19 respiratory function. This case illustrates that patients with severe lung parenchymal destruction due to advanced LAM are at risk of worsening hypoxemia, but may not have a bad outcome if managed appropriately. Prevention and early diagnosis of COVID-19 are crucial in patients with advanced LAM. Future studies are needed to improve understanding of the clinical features and optimal treatment of COVID-19 in patients with LAM.

The Mitochondrial Outer Membrane Protein Tom70-Mediator in Protein Traffic, Membrane Contact Sites and Innate Immunity.

Tom70 is a versatile adaptor protein of 70 kDa anchored in the outer membrane of mitochondria in metazoa, fungi and amoeba. The tertiary structure was resolved for the Tom70 of yeast, showing 26 α-helices, most of them participating in the formation of 11 tetratricopeptide repeat (TPR) motifs. Tom70 serves as a docking site for cytosolic chaperone proteins and co-chaperones and is thereby involved in the uptake of newly synthesized chaperone-bound proteins in mitochondrial biogenesis. In yeast, Tom70 additionally mediates ER-mitochondria contacts via binding to sterol transporter Lam6/Ltc1. In mammalian cells, TOM70 promotes endoplasmic reticulum (ER) to mitochondria Ca2+ transfer by association with the inositol-1,4,5-triphosphate receptor type 3 (IP3R3). TOM70 is specifically targeted by the Bcl-2-related protein MCL-1 that acts as an anti-apoptotic protein in macrophages infected by intracellular pathogens, but also in many cancer cells. By participating in the recruitment of PINK1 and the E3 ubiquitin ligase Parkin, TOM70 can be implicated in the development of Parkinson's disease. TOM70 acts as receptor of the mitochondrial antiviral-signaling protein (MAVS) and thereby participates in the corresponding system of innate immunity against viral infections. The protein encoded by Orf9b in the genome of SARS-CoV-2 binds to TOM70, probably compromising the synthesis of type I interferons.

The PIKfyve Inhibitor Apilimod: A Double-Edged Sword against COVID-19.

The PIKfyve inhibitor apilimod is currently undergoing clinical trials for treatment of COVID-19. However, although apilimod might prevent viral invasion by inhibiting host cell proteases, the same proteases are critical for antigen presentation leading to T cell activation and there is good evidence from both in vitro studies and the clinic that apilimod blocks antiviral immune responses. We therefore warn that the immunosuppression observed in many COVID-19 patients might be aggravated by apilimod.