Design and synthesis of novel ß-carboline-bisindole hybrids as potential anticancer agents.

We are reporting a short and convenient pathway for the synthesis of novel ß-carboline-bisindole hybrid compounds from relatively cheap and commercially available chemicals such as tryptamine, dialdehydes and indoles. These newly designed compounds can also be prepared in high yields with the tolerance of many functional groups under mild conditions. Notably, these ß-carboline-bisindole hybrid compounds exhibited some promising applications as anticancer agents against the three common cancer cell lines MCF-7 (breast cancer), SK-LU-1 (lung cancer), and HepG2 (liver cancer). The two best compounds 5b and 5g inhibited the aforementioned cell lines with the same range of the reference Ellipticine at less than 2 µM. A molecular docking study to gain more information about the interactions between the synthesized molecules and the kinase domain of the EGFR was performed. Therefore, this finding can have significant impacts on the development of future research in medicinal chemistry and drug discovery.

Economically viable co-production of methanol and sulfuric acid via direct methane oxidation.

The direct oxidation of methane to methanol has been spotlighted research for decades, but has never been commercialized. This study introduces cost-effective process for co-producing methanol and sulfuric acid through a direct oxidation of methane. In the initial phase, methane oxidation forms methyl bisulfate (CH3OSO3H), then transformed into methyl trifluoroacetate (CF3CO2CH3) via esterification, and hydrolyzed into methanol. This approach eliminates the need for energy-intensive separation of methyl bisulfate from sulfuric acid by replacing the former with methyl trifluoroacetate. Through the superstructure optimization, our sequential process reduces the levelized cost of methanol to nearly two-fold reduction from the current market price. Importantly, this process demonstrates adaptability to smaller gas fields, assuring its economical operation across a broad range of gas fields. The broader application of this process could substantially mitigate global warming by utilizing methane, leading to a significantly more sustainable and economically beneficial methanol industry.

Efficacy of Enhanced Recovery After Surgery Program for Patients Undergoing Lobectomy for Lung Cancer: A Scoping Review and Single-Center Initial Result in Vietnam.

Surgery for lung cancer can be invasive and the recovery process is often slow with many complications. To address this, the enhanced recovery after surgery (ERAS) program aims to minimize adverse clinical events for surgical patients. This is achieved through a multimodal perioperative care protocol that aims to preserve preoperative organ function and reduce postoperative complications. Initially applied to gastrointestinal surgery, this model has now been expanded to other major surgeries, including lung surgery. Through a review of seven retrospective and prospective cohort observational studies, we have examined the effects of the ERAS program on patients undergoing lobectomy for lung cancer treatment. Our analysis focused on outcomes such as length of stay, re-operation rate, re-admission rate, postoperative mortality, and costs, providing valuable insights into the real clinical practice setting. We also report on some initial results when applying ERAS at University Medical Center Ho Chi Minh City.

Malnutrition screening tool use in a New Zealand hospital: Reliability and rates of malnutrition screening on admission.

AIMS: This research aimed to assess the rate and reliability of routine nurse-completed malnutrition screening and report the prevalence of malnutrition risk on admission to Christchurch Hospital. METHODS: Student dietitians administered the Malnutrition Screening Tool to patients in three speciality wards within 48 h of admission. Student dietitians' Malnutrition Screening Tool scores were compared against documented nurse-completed Malnutrition Screening Tool scores. Data were analysed using descriptive statistics, Fisher's exact test, and Cohen's kappa tests (interrater reliability ⱪ). A p-value <0.05 was considered statistically significant. RESULTS: Student dietitians, using the Malnutrition Screening Tool, screened 360 (96%) of 377 eligible patients while nurses screened 332 (88%) patients. Student dietitians and nurses screened 119 patients (33%) and 63 patients (18%) respectively at risk of malnutrition. There was fair agreement (ⱪ = 0.311) in Malnutrition Screening Tool total scores between nurses and student dietitians. There was a significant difference in the proportion of patients screened at risk of malnutrition between nurses and student dietitians (p < 0.0001). CONCLUSION: Malnutrition risk remains high in acute care settings. Nurses were less likely to screen patients as at risk of malnutrition than student dietitians. Regular support and training in using Malnutrition Screening Tool may help improve the rate and reliability of routine malnutrition screening.

The effects of wholegrain processing on appetite: randomised crossover trial in adults with type 2 diabetes.

Aims: Recent observational data indicate higher ultra-processed food intakes are associated with a broad range of adverse health outcomes. Experimental studies on why this might be are lacking. We have considered the effects of wholegrain processing on measures of appetite in free-living adults with type 2 diabetes. Materials and methods: Participants were randomised to two interventions of two-weeks duration, separated by washout. Interventions were nutrient-matched wholegrain foods that differed by the amount of processing. Self-reported hunger and satiety were indicated on visual analogue scales before or after meals for four days at baseline and the end of each intervention. Metabolite markers of appetite were measured pre and post intervention in fasting plasma. Results: 31 adults (63 ± 13 years old, BMI 32.4 ± 7, HbA1c 7.5 ± 3.4% (59 ± 14 mmol mol-1)) commenced the trial, 28 (90%) completed both interventions. Wholegrain consumption, as measured by alkylresorcinols, was balanced between interventions. Self-reported pre-meal hunger was consistently lower at breakfast (MD, mean difference 0.49/10 95% CI 0.03 to 0.94), lunch (MD 0.67/10 95% CI 0.09 to 1.25), and dinner (MD -0.71/10 95% CI 0.19 to 1.23) during the intervention of less processed whole grains when compared with pre-intervention measures, however this did not result in a difference between interventions. Change in metabolite markers of appetite did not differ between interventions. Conclusions: A significant difference in hunger or satiety between less and more processed whole grains over intervention periods of two weeks was not detected within the current trial. Further experimental studies are needed to consider the potential effects of food processing on physiological processes such as appetite to provide mechanistic understanding behind observations of highly processed food intakes and adverse health outcomes.

Pathophysiological Mechanisms of Cardiac Dysfunction in Transgenic Mice with Viral Myocarditis.

Viral myocarditis is pathologically associated with RNA viruses such as coxsackievirus B3 (CVB3), or more recently, with SARS-CoV-2, but despite intensive research, clinically proven treatment is limited. Here, by use of a transgenic mouse strain (TG) containing a CVB3ΔVP0 genome we unravel virus-mediated cardiac pathophysiological processes in vivo and in vitro. Cardiac function, pathologic ECG alterations, calcium homeostasis, intracellular organization and gene expression were significantly altered in transgenic mice. A marked alteration of mitochondrial structure and gene expression indicates mitochondrial impairment potentially contributing to cardiac contractile dysfunction. An extended picture on viral myocarditis emerges that may help to develop new treatment strategies and to counter cardiac failure.

Outcome and toxicity of chemoradiation using volumetric modulated arc therapy followed by 3D image-guided brachytherapy for cervical cancer: Vietnam National Cancer Hospital experience.

Background: Volumetric modulated arc therapy (VMAT) and 3D image-guided brachytherapy (3D-IGBT) have recently been introduced in Vietnam for the treatment of locally advanced cervical cancer. This study aims to assess the outcomes and toxicities of chemoradiation using VMAT followed by 3D-IGBT in Vietnamese cervical cancer patients. Materials and methods: A prospective interventional study on 72 patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB3-IIIC2 disease who underwent concurrent chemoradiation using VMAT, followed by 3D-IGBT according to EMBRACE-II protocol. Primary endpoints were locoregional control; secondary endpoints were systemic control and toxicity. Results: Median body volume received 43 Gy was 1589.1 cm3 (range 1214.8-2574.8). Median high-risk clinical target volume (CTV-HR) was 18.8 cm3 (range 8.6-61.2) with a median dose to 90% (D90) of CTV-HR of 90.6 Gy (range 86.8-99.6). Mean doses to 2cc (D2cc) of bladder, rectum, and sigmoid were 75.8, 55.2, and 62.1 Gy, respectively. At median 19-month follow-up (range 12-25), locoregional control and systemic control were 95.8% and 81.9%, respectively. Systemic control was the lowest in N2 disease (54.5%). Grade ≥ 3 acute toxicities were less than 10%, except neutropenia (31.9%). Extended-field radiation increased significantly nausea, fatigue, and thrombocytopenia. No grade ≥ 3 proctitis or cystitis; 8.3% had grade 3 vaginal stenosis. Conclusions: VMAT-based chemoradiation therapy followed by 3D-IGBT achieved high locoregional control with manageable toxicities in locally advanced cervical cancer. Systemic control correlated with disease stage.

Variations in length-weight relationship, growth and body condition of the commercial mullet Ellochelon vaigiensis in the Vietnamese Mekong Delta.

The Squaretail mullet Ellochelon vaigiensis is widely found from marine to brackish and freshwater, including the Vietnamese Mekong Delta (VMD). Data on the length-weight relationships (LWRs), growth pattern, and condition factor (CF) play an essential role in fisheries assessment but are limited to E. vaigiensis - a commercial fish in VMD. To better understand the growth pattern of this fish, the study collected samples at four sites, including Thanh Phu, Ben Tre (BT); Duyen Hai, Tra Vinh (TV); Tran De, Soc Trang (ST); and Dong Hai, Bac Lieu (BL). Each month, fish samples were collected using bottom nets at each sampling site during high tide in both the dry season (January to May 2021) and the wet season (November to December 2020 and June to October 2021). This study qualified whether LWRs, growth pattern, and CF of E. vaigiensis vary with sexual, intraspecific, and spatiotemporal variables. The analysis results of 942 specimens showed that fish total length (TL = 17.86 ± 0.13 cm) and weight (W = 54.29 ± 1.05 g) changed with sex, season, month and site. The W could be appraised from a given TL due to high coefficients (r 2 ) of LWRs that were regulated by fish size and season but not sex. The species showed negative allometry as its slope value of LWRs (b = 2.34 ± 0.30) was <3. The growth pattern did not change with sex and site but varied fish size, season, and months ranging from negative allometry to isometry. The CF of females (1.08 ± 0.01) was higher than males (0.99 ± 0.01). Albeit this fish showed spatiotemporal variation in CF, ranging from 0.81 ± 0.01 to 1.25 ± 0.02, the CF (1.02 ± 0.01) was significantly higher than the one threshold, indicating that E. vaigiensis lived a favorable condition. Research results show that this fish species has a dominant growth pattern in terms of length (b < 3) and is well adapted to the environment (CF ≈ 1). These data have an important role in suggesting the future aquaculture of this fish.

Cu-catalyzed Synthesis of Quinolines by Dehydrogenative Reaction of 2-Aminobenzyl Alcohol and Ketones: A Combined Experimental and Computational Study.

Quinoline derivatives are important moieties in bioactive molecules and advanced materials. However, an efficient strategy to synthesize quinoline derivatives remains challenging. Herein, we describe an efficient and practical method for the synthesis of quinolines by Cu-catalyzed cyclization of 2-amino benzyl alcohol with ketones (or secondary alcohols) via an acceptorless dehydrogenation pathway. Interestingly, a range of highly functionalized quinolines is prepared in good yields using low catalyst loading under relatively mild conditions. Furthermore, density functional theory (DFT) calculations are carried out to investigate mechanistic insights for the acceptorless dehydrogenation pathway.

Genome-Wide Identification and Analysis of Genes Encoding Putative Heat Shock Protein 70 in Papaya (Carica papaya).

<b>Background and Objective:</b> In high plants, the 70 kDa heat stress proteins (Hsp70-s) have been regarded as one of the vital components of the cellular network of chaperones and folding catalysts that play important roles in numerous biological processes during growth and development. The Hsp70 families have been reported in many plant species, unfortunately, no information on this important protein family in papaya (<i>Carica papaya</i>). The objective of this study was to provide comprehensive information on the CpHsp70 family in papaya. <b>Materials and Methods:</b> The <i>CpHsp70</i> genes in the papaya genome were identified by a basic local alignment search tool against the papaya genome database by using well-known <i>Arabidopsis</i> Hsp70-s. Sequences were then analyzed by various bioinformatics tools to investigate the characteristics of the CpHsp70 family. <b>Results:</b> A total of 12 members of the CpHsp70 family has been identified and characterized in papaya. By using various computational tools, these results revealed that all general characteristics of the CpHsp70 family, like physic-chemical parameters, gene structure, phylogenetic tree and subcellular localization were provided. The transcriptome atlas was applied to re-analyze the expression patterns of genes encoding the CpHsp70 family in major tissues/organs during the growth and development of papaya plants. <b>Conclusion:</b> Results from this work exhibited the characteristics and expression analysis of the <i>CpHsp70</i> genes of this important tropical fruit crop. Taken together, this study could provide a solid foundation of the CpHsp70 family, which will be helpful in the construction of stress tolerance in papaya plants.

Single-incision endoscopic-assisted temporoparietal fascia harvest for single stage auricular reconstruction.

INTRODUCTION: The temporoparietal fascia flaps (TPFF) have been widely used to cover the framework in auricular reconstructions. However, flap harvesting is mostly done by open surgery which may be easier but often results in bad scarring and hair loss. We would like to present a series of cases using endoscopic-assisted flap harvesting techniques with only one single cosmetic auricular incision. PATIENTS AND METHODS: Prospective studies from June 2018 to September 2021 on patients who underwent single-stage total auricular reconstruction using autologous costal cartilage and porous polyethylene (PPE) framework. Variables include age, gender, flap survivability as well as visual results and complications. RESULTS: A total of 61 TPFFs were harvested to cover 15 autologous costal cartilages and 46 PPE frameworks in 60 patients (one patient had operation on both sides). TPFF harvests are performed by endoscopic techniques with one single auricular incision. There was no flap necrosis, no bleeding and no cases required framework removal. Only 7/61 (11.5%) ears had small framework exposure which resolved on their own or only required local skin flap coverage and 1 ear had frontal nerve injury. CONCLUSION: Single-stage auricular reconstruction is a difficult surgery, yet greatly beneficial to young children. Through a single-incision endoscopic technique, we can obtain sufficiently large high-survivability TPFFs ensuring full coverage of the autologous costal cartilage or PPE framework. This method is reliable, and reproducible with advanced training. After reviewing the literature, we can state that our report probably includes the largest endoscopic-assisted TPFF harvesting series and the first to implement single-incision endoscopic technique in auricular reconstructions.

A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA (BNT162b2/mRNA-1273) and adenovirus vectored vaccines (ChAdOx1-S) after the first, second and third doses

We longitudinally profiled immune responses in 102 adults who received BNT162b2 (Pfizer-BioNTech) or ChAdOx1-S (Oxford-AstraZeneca) as their primary vaccinations. Bloods were collected pre-vaccination, 1-7 days after the 1st, 2nd and 3rd doses (BNT162b2 or mRNA-1273) to assess innate and early adaptive responses, and [~]28 days after the 2nd and 3rd doses to assess immunogenicity. Using a multi-omics approach including RNAseq, cytokine multiplex assay, proteomics, lipidomics, and flow cytometry we identified key differences in the immune responses induced by the ChAdOx1-S and BNT162b2 vaccines that were correlated with subsequent antigen-specific antibody and T cell responses or vaccine reactogenicity. We observed that vaccination with ChAdOx1-S but not BNT162b2 induced a memory-like response after the first dose, which was correlated with the expression of several proteins involved in complement and coagulation. The COVID-19 Vaccine Immune Responses Study (COVIRS) thus represents a major resource to understand the immunogenicity and reactogenicity of these COVID-19 vaccines.

Virus-induced inhibition of cardiac pacemaker channel HCN4 triggers bradycardia in human-induced stem cell system.

The enterovirus Coxsackievirus B3 (CVB3) is known to be a major source for the development of cardiac dysfunctions like viral myocarditis (VMC) and dilatative cardiomyopathy (DCM), but also results in bradycardia and fatal cardiac arrest. Besides clinical reports on bradycardia and sudden cardiac death, very little is known about the influence of CVB3 on the activity of human cardiac pacemaker cells. Here, we address this issue using the first human induced pluripotent stem cell (hiPSC)-derived pacemaker-like cells, in which the expression of a transgenic non-infectious variant of CVB3 can be controlled dose- and time-dependently. We found that CVB3 drastically changed hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) distribution and function in hiPSC-derived pacemaker-like tissue. In addition, using HCN4 cell expression systems, we found that HCN4 currents were decreased with altered voltage dependency of activation when CVB3 was expressed. Increased autophagosome formation and autophagosomal HCN4 insertion was observed in hiPSC-derived pacemaker-like cells under CVB3 expression as well. Individual effects of single, non-structural CVB3 proteins were analyzed and demonstrated that CVB3 proteins 2C and 3A had the most robust effect on HCN4 activity. Treatment of cells with the Rab7 inhibitor CID 106770 or the CVB3-3A inhibitor GW5074 led to the recovery of the cytoplasmatic HCN4 accumulation into a healthy appearing phenotype, indicating that malfunctioning Rab7-directed autophagosome transport is involved in the disturbed, cytoplasmatic HCN4 accumulation in CVB3-expressing human pacemaker-like cells. Summarizing, the enterovirus CVB3 inhibits human cardiac pacemaker function by reducing the pacemaker channel plasma membrane density, an effect that can be corrected by pharmacological intervention of endocytic vesicle trafficking.

SWEET Gene Family in Sugar Beet (Beta vulgaris): Genome-Wide Survey, Phylogeny and Expression Analysis.

<b>Background and Objective:</b> The SWEET (Sugars Will Eventually be Exported Transporter) proteins play important roles in modulating the growth and development processes in plants. However, little information is available on the SWEET family in sugar beet (<i>Beta vulgaris</i>). The objectives of this present study were to genome-wide identify and characterize the BvSWEET family in sugar beet. <b>Materials and Methods:</b> Based on the available genome, proteome and transcriptome databases of sugar beet, various computational tools have been used to analyze the nucleotide and full-length protein sequences of members of the BvSWEET family. <b>Results:</b> A total of 16 members of the BvSWEET family has been identified in sugar beet at the genome-wide scale. Structural analysis indicated that the BvSWEET family exhibited variable characteristics. Furthermore, the BvSWEET family in sugar beet could be categorized into four distinct groups like in other plant species. Of our interest, we found that some <i>BvSWEET</i> genes exhibited strongly preferential expression in major organs/tissues under adverse environmental stimuli. <b>Conclusion:</b> The results provided a comprehensive foundation for further functional characterization of the <i>BvSWEET </i>gene family.

Effect of NPK-SRFS on the Growth, Yield and Essential Oil Composition of Basil (Ocimum basilicum L.).

<b>Background and Objective:</b> Basil (<i>Ocimum basilicum</i> L.), an aromatic herb, is considered one of the most important crops with essential oils as well as other bioactive compounds. Basil leaves have tremendous pharmaceutical benefits and are used for foods. Slow-release fertilizers have been developed to optimize the fertilization of crops. This work aims to discover the effect of NPK Slow-Release Fertilizer Coated by Starch (NPK-SRFS) at different rates on growth, yield and essential oil components of basil grown on the field in Northern Vietnam. <b>Materials and Methods:</b> Basil seedlings, sown from seeds, were used as plant materials. NPK-SRFS was stocked in the Faculty of Chemistry, Hanoi Pedagogical University 2. The experiments were designed in a fully randomized block model, consisting of four treatments with different rates of NPK-SRFS. Each treatment had three replicates with an area of 8 m². Duncan's Multiple Range Test was being used for statistical analysis (p = 0.05). <b>Results:</b> All 3 NPK-SRFS treatments significantly increased the number of buds and leaves per plant compared to the control. However, NPK-SRFS at different rates affected diversely plant height and leaf area of the basil. F5.0 and F10 treatments accelerated chlorophyll content as well as Fv/Fm value in comparison with none NPK-SRFS treatment. The application of NPK-SRFS at different rates caused slightly different changes in basil essential oil composition, especially the content of Methyl Chavicol, the most abundant oxygenated monoterpene and α-trans-Bergamotene, the most abundant sesquiterpene hydrocarbon. <b>Conclusion:</b> The present study provides further insight into the influence of NPK-SRFS on the growth, yield and essential oil components of basil.

Semi-nested RT-PCR enables sensitive and high-throughput detection of SARS-CoV-2 based on melting analysis.

BACKGROUND: Asymptomatic transmission was found to be the Achilles' heel of the symptom-based screening strategy, necessitating the implementation of mass testing to efficiently contain the transmission of COVID-19 pandemic. However, the global shortage of molecular reagents and the low throughput of available realtime PCR facilities were major limiting factors. METHODS: A novel semi-nested and heptaplex (7-plex) RT-PCR assay with melting analysis for detection of SARS-CoV-2 RNA has been established for either individual testing or 96-sample pooled testing. The complex melting spectrum collected from the heptaplex RT-PCR amplicons was interpreted with the support of an artificial intelligence algorithm for the detection of SARS-CoV-2 RNA. The analytical and clinical performance of the semi-nested RT-PCR assay was evaluated using RNAs synthesized in-vitro and those isolated from nasopharyngeal samples. RESULTS: The LOD of the assay for individual testing was estimated to be 7.2 copies/reaction. Clinical performance evaluation indicated a sensitivity of 100% (95% CI: 97.83-100) and a specificity of 99.87% (95% CI: 99.55-99.98). More importantly, the assay supports a breakthrough sample pooling method, which makes possible parallel screening of up to 96 samples in one real-time PCR well without loss of sensitivity. As a result, up to 8,820 individual pre-amplified samples could be screened for SARS-CoV-2 within each 96-well plate of realtime PCR using the pooled testing procedure. CONCLUSION: The novel semi-nested RT-PCR assay provides a solution for highly multiplex (7-plex) detection of SARS-CoV-2 and enables 96-sample pooled detection for increase of testing capacity. .

Dietary fibre in hypertension and cardiovascular disease management: systematic review and meta-analyses.

BACKGROUND: Higher dietary fibre intakes are associated with a reduced risk of developing cardiovascular disease (CVD), and increasing intake has been shown to reduce blood pressure and other cardiometabolic risk factors. The extent to which dietary fibre can further reduce risk for those with CVD and treated with cardioprotective drugs has not been clearly established. We have examined the evidence for dietary fibre as adjunct therapy in those with CVD or hypertension. METHODS: Ovid MEDLINE, Embase, PubMed, and CENTRAL were searched to June 2021. Prospective observational studies reporting on fibre intakes and mortality in those with pre-existing CVD and controlled trials of increasing fibre intakes on cardiometabolic risk factors in those with CVD or hypertension were eligible. Outcomes were mortality (studies) and cardiometabolic risk factors (trials). Data synthesis was with random effects and dose response. Certainty of evidence was assessed using GRADE. RESULTS: Three prospective studies including 7469 adults with CVD, and 12 trials of 878 adults with CVD or hypertension were identified. Moderate certainty evidence indicates reduced all-cause mortality (relative risk, RR0.75 (95% confidence interval, CI 0.58-0.97)) when comparing higher with lower fibre intakes. Low certainty evidence from trials of adults with cardiovascular disease indicates increasing fibre intakes reduced total (mean difference, MD - 0.42 mmol/L (95%CI - 0.78 to - 0.05) and low-density lipoprotein (LDL) cholesterol (MD - 0.47mmol/L (95%CI - 0.85 to - 0.10)). High certainty evidence from trials of adults with hypertension indicates increasing fibre intakes reduces systolic (MD 4.3 mmHg (95% CI 2.2 to 5.8)) and diastolic blood pressure (MD 3.1 mmHg (95% CI 1.7 to 4.4)). Moderate and low certainty evidence indicated improvements in fasting blood glucose (MD 0.48 mmol/L (- 0.91 to - 0.05)) and LDL cholesterol (MD 0.29 mmol/L (95% CI 0.17 to 0.40)). Benefits were observed irrespective of cardioprotective drug use. CONCLUSIONS: These findings emphasise the likely benefits of promoting greater dietary fibre intakes for patients with CVD and hypertension. Further trials and cohort analyses in this area would increase confidence in these results.

Virus-Host Interactions of Enteroviruses and Parvovirus B19 in Myocarditis.

Viral diseases are a major threat to modern society and the global health system. It is therefore of utter relevance to understand the way viruses affect the host as a basis to find new treatment solutions. The understanding of viral myocarditis (VMC) is incomplete and effective treatment options are lacking. This review will discuss the mechanism, effects, and treatment options of the most frequent myocarditis-causing viruses namely enteroviruses such as Coxsackievirus B3 (CVB3) and Parvovirus B19 (PVB19) on the human heart. Thereby, we focus on: 1. Viral entry: CVB3 use Coxsackievirus-Adenovirus-Receptor (CAR) and Decay Accelerating Factor (DAF) to enter cardiac myocytes while PVB19 use the receptor globoside (Gb4) to enter cardiac endothelial cells. 2. Immune system responses: The innate immune system mediated by activated cardiac toll-like receptors (TLRs) worsen inflammation in CVB3-infected mouse hearts. Different types of cells of the adaptive immune system are recruited to the site of inflammation that have either protective or adverse effects during VMC. 3. Autophagy: CVB3 evades autophagosomal degradation and misuses the autophasomal pathway for viral replication and release. 4. Viral replication sites: CVB3 promotes the formation of double membrane vesicles (DMVs), which it uses as replication sites. PVB19 uses the host cell nucleus as the replication site and uses the host cell DNA replication system. 5. Cell cycle manipulation: CVB3 attenuates the cell cycle at the G1/S phase, which promotes viral transcription and replication. PVB19 exerts cell cycle arrest in the S phase using its viral endonuclease activity. 6. Regulation of apoptosis: Enteroviruses prevent apoptosis during early stages of infection and promote cell death during later stages by using the viral proteases 2A and 3C, and viroporin 2B. PVB19 promotes apoptosis using the non-structural proteins NS1 and the 11 kDa protein. 7. Energy metabolism: Dysregulation of respiratory chain complex expression, activity and ROS production may be altered in CVB3- and PVB19-mediated myocarditis. 8. Ion channel modulation: CVB3-expression was indicated to alter calcium and potassium currents in Xenopus laevis oocytes and rodent cardiomyocytes. The phospholipase 2-like activity of PVB19 may alter several calcium, potassium and sodium channels. By understanding the general pathophysiological mechanisms of well-studied myocarditis-linked viruses, we might be provided with a guideline to handle other less-studied human viruses.

Myocardial Damage by SARS-CoV-2: Emerging Mechanisms and Therapies.

Evidence is emerging that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect various organs of the body, including cardiomyocytes and cardiac endothelial cells in the heart. This review focuses on the effects of SARS-CoV-2 in the heart after direct infection that can lead to myocarditis and an outline of potential treatment options. The main points are: (1) Viral entry: SARS-CoV-2 uses specific receptors and proteases for docking and priming in cardiac cells. Thus, different receptors or protease inhibitors might be effective in SARS-CoV-2-infected cardiac cells. (2) Viral replication: SARS-CoV-2 uses RNA-dependent RNA polymerase for replication. Drugs acting against ssRNA(+) viral replication for cardiac cells can be effective. (3) Autophagy and double-membrane vesicles: SARS-CoV-2 manipulates autophagy to inhibit viral clearance and promote SARS-CoV-2 replication by creating double-membrane vesicles as replication sites. (4) Immune response: Host immune response is manipulated to evade host cell attacks against SARS-CoV-2 and increased inflammation by dysregulating immune cells. Efficiency of immunosuppressive therapy must be elucidated. (5) Programmed cell death: SARS-CoV-2 inhibits programmed cell death in early stages and induces apoptosis, necroptosis, and pyroptosis in later stages. (6) Energy metabolism: SARS-CoV-2 infection leads to disturbed energy metabolism that in turn leads to a decrease in ATP production and ROS production. (7) Viroporins: SARS-CoV-2 creates viroporins that lead to an imbalance of ion homeostasis. This causes apoptosis, altered action potential, and arrhythmia.

Long-pulsed 1064-nm and 755-nm lasers for C1 leg veins on skin type IV patients: a side-by-side comparison.

Long-pulsed 1064-nm (LP1064) and 755-nm (LP755) lasers have been demonstrated as effective treatments for leg veins. However, few studies of these treatments on Asian skin type as well as direct comparison between two methods were reported. The aim of this study was to compare the clinical efficacy and safety of LP1064 with LP755 in the treatment of C1 leg veins on skin type IV patients. Patients with symmetric matched areas C1 leg veins were treated with single session of LP1064 for the right and LP755 for the left. Treated areas of every patient were divided into matrices of 2 × 2 cm squares. Vessels in the highest density squares were subjected to evaluation. Spot sizes were 5 mm fixed. Pulse durations and fluences were according to vessel diameters and endpoints, respectively. The clearances were evaluated at 1 and 3 months post treatment. Side effects were recorded immediately, 10 min, 24 h, and 1 and 3 months after treatment. Twenty-two patients were enrolled with total 96 vessels from 22 selected squares in the right and 106 vessels from 22 selected squares in the left. At 1-month follow-up, the clearances of LP1064 and LP755 were not significantly different (71.87% and 71.69%, respectively; p = 0.99). At 3-month follow-up, the efficacies were constant and no recurrence occurred. Pain levels of both methods were moderate and significantly lower in LP755. These findings suggest that LP1064 and LP755 laser treatments were comparatively effective and safe for C1 leg veins of skin type IV patients.