Targeting the receptor binding domain and heparan sulfate binding for antiviral drug development against SARS-CoV-2 variants.

The emergence of SARS-CoV-2 variants diminished the efficacy of current antiviral drugs and vaccines. Hence, identifying highly conserved sequences and potentially druggable pockets for drug development was a promising strategy against SARS-CoV-2 variants. In viral infection, the receptor-binding domain (RBD) proteins are essential in binding to the host receptor. Others, Heparan sulfate (HS), widely distributed on the surface of host cells, is thought to play a central role in the viral infection cycle of SARS-CoV-2. Therefore, it might be a reasonable strategy for antiviral drug design to interfere with the RBD in the HS binding site. In this study, we used computational approaches to analyze multiple sequences of coronaviruses and reveal important information about the binding of HS to RBD in the SARS-CoV-2 spike protein. Our results showed that the potential hot-spots, including R454 and E471, in RBD, exhibited strong interactions in the HS-RBD binding region. Therefore, we screened different compounds in the natural product database towards these hot-spots to find potential antiviral candidates using LibDock, Autodock vina and furthermore applying the MD simulation in AMBER20. The results showed three potential natural compounds, including Acetoside (ACE), Hyperoside (HYP), and Isoquercitrin (ISO), had a strong affinity to the RBD. Our results demonstrate a feasible approach to identify potential antiviral agents by evaluating the binding interaction between viral glycoproteins and host receptors. The present study provided the applications of the structure-based computational approach for designing and developing of new antiviral drugs against SARS-CoV-2 variants.

Clinical Effect of Moisturized Skin Care on Radiation Dermatitis of Head and Neck Cancer.

BACKGROUND/AIM: Radiation therapy (RT) for head and neck cancer may cause severe radiation dermatitis (RD) resulting in RT interruption and affecting disease control. A few studies address skin moisture changes during RT for head and neck cancer. The purpose of this study was to explore the effect of moisturized skin care (MSC) on severity of RD. PATIENTS AND METHODS: The study includes newly diagnosed head and neck cancer patients undergoing RT. Participants were divided into MSC group and routine skin care (RSC) group based on patient's preferred decision. Skin moisture in the four quadrants of the neck was measured weekly before and after RT. RD was assessed with the Radiation Induced Skin Reaction Assessment Scale (RISRAS) and the Radiation Therapy Oncology Group (RTOG) acute skin toxicity grading criteria. RESULTS: A total of 54 patients were enrolled, of which 49 patients were suitable for the statistical analysis. There was a statistically significant difference in the RISRAS total score since the 5th week after RT between the groups. The severity of RD was less (B=0.814, p=0.021) and the onset was later (B=-0.384, p=0.006) in the MSC group when compared to the RSC group. Skin moisture decreased with cumulative radiation dose. In the upper neck, the MSC group had a slower rate of skin moisture decrease compared to the RSC group (right upper neck: B=0.935, p=0.007; left upper neck: B=0.93, p=0.018). CONCLUSION: MSC can effectively reduce the severity and delay the onset of RD, while slows down skin moisture decrease during RT.

Umbelliferone and eriodictyol suppress the cellular entry of SARS-CoV-2.

BACKGROUND: Artemisia argyi (A. argyi), also called Chinese mugwort, has been widely used to control pandemic diseases for thousands of years since ancient China due to its anti-microbial infection, anti-allergy, and anti-inflammation activities. Therefore, the potential of A. argyi and its constituents in reducing the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was investigated in this study. RESULTS: Among the phytochemicals in A. argyi, eriodictyol and umbelliferone were identified to target transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) proteins, the essential factors for the cellular entry of SARS-CoV-2, in both FRET-based enzymatic assays and molecular docking analyses. These two ingredients of A. argyi suppressed the infection of ACE2-expressed HEK-293 T cells with lentiviral-based pseudo-particles (Vpp) expressing wild-type and variants of SARS-CoV-2 spike (S) protein (SARS-CoV-2 S-Vpp) via interrupting the interaction between S protein and cellular receptor ACE2 and reducing the expressions of ACE2 and TMPRSS2. Oral administration with umbelliferone efficiently prevented the SARS-CoV-2 S-Vpp-induced inflammation in the lung tissues of BALB/c mice. CONCLUSIONS: Eriodictyol and umbelliferone, the phytochemicals of Artemisia argyi, potentially suppress the cellular entry of SARS-CoV-2 by preventing the protein binding activity of the S protein to ACE2.

Resectable fusiform internal jugular vein aneurysm with vascular excision and bypass with an 8 mm Maquet graft: A case report.

RATIONALE: Venous aneurysm is a rare vascular disease. Studies reveal that patients with fusiform internal jugular vein aneurysms are not suitable for embolization. PATIENT CONCERNS: Two treatment options are considered, either bypass the aneurysm via stenting or excision of the lesion site and anastomosis using an artificial graft. The advantages of excision bypass include the absence of endoleak and stent migration; however, a larger wound and longer operation time are required for it. DIAGNOSES: Physical examination revealed a swelling in the right neck area. Head and neck computed tomography was performed for the survey. It revealed a 27.22 × 25.07 × 58.17 mm internal jugular fusiform aneurysm. INTERVENTIONS: Vein excision was performed while using hemoclamps to control inflow and outflow, and a graft was anastomosed for bypass using an 8 mm Maquet graft. OUTCOMES: The wound recovery was favorable, with no signs of infection, and the pain was under control. LESSONS: The patient had a contrast-enhanced head and neck computed tomography, and the images efficiently diagnosed a venous aneurysm. This patient had refractory pain, which was a significant indication of the operation. We decided by ourselves on the duration of the interval of following up. We used excision and bypassing with graft, and the result was beneficial.

A young Asian woman with thrombosis in the right renal vein and inferior vena cava: A rare case report and literature review.

INTRODUCTION: Renal vein thrombosis (RVT) is a rare clinical entity wherein a blood clot forms in one of the major renal veins or its tributaries. Patients with certain risk factors, such as adults with nephrotic syndrome and infants with dehydration, are susceptible to developing it. PATIENT CONCERNS: We present a young woman with primary thrombosis in the right renal vein and inferior vena cava. Hormonal therapy and the reception of the Medigen Vaccine Biologics Corporation coronavirus disease 2019 vaccine were the suspected risk factors for developing this disease. PRIMARY DIAGNOSIS, INTERVENTIONS, OUTCOMES: The primary thrombosis in the right renal vein and inferior vena cava was diagnosed using abdominal computed tomography (CT), and 90% of the thrombus in the right renal vein was dissolved after ultrasound-assisted catheter-directed thrombolysis followed by urokinase infusion for 1 week. Antibiotics and rivaroxaban were prescribed for 3 days and 5 months, respectively. Cryoprecipitate transfusions based on the level of fibrinogen were also prescribed. No long-term complications were noted in the clinic visits. We demonstrate the results of ultrasound-assisted catheter-directed thrombolysis using urokinase infusion for thrombosis in the right renal vein and inferior vena cava. Lastly, we review the literature discussing RVT relevant to this case. CONCLUSION: This study reveals the successful use of the novel technique, ultrasound-assisted catheter-directed thrombolysis using urokinase infusion, for the treatment of RVT.

Vascular Trauma in the Extremities: Factors Associated with the Outcome and Assessment of Amputation Indexes.

Background: Traumatic vascular injury in the extremities may be associated with a low mortality rate but can lead to limb loss that seriously affects patients' functionality. Multiple scoring systems have been designed to evaluate the prognosis, but none are 100% predictive. The management of traumatic vascular injury remains challenging and depends mostly on the surgeon's experience. Objectives: We identified the risks associated with limb loss and further investigated the utility of current amputation indexes. Methods: We retrospectively reviewed 53 cases of traumatic vascular injury in the extremities at a tertiary referral medical center over the past ten years (January 2011-December 2020). The mangled extremity severity score (MESS), limb salvage index (LSI), and predictive salvage index (PSI) were used to assess the traumatized limbs. The injury characteristics and outcomes were evaluated using regression analysis. Results: The incidence of limb loss was 20.8% (n = 11), and open fractures were the most related factor. Extensive involvement of soft tissue, vascular injury combined with tibia or fibula fractures, initial shock status, and the amount of transfusion were associated with limb loss. Conclusions: Our study identified the risk factors and clinical utility of MESS, PSI, and LSI. While both LSI and PSI had acceptable diagnostic accuracy, amputation should be decided based on a variety of criteria and clinical features. Salvaging any limb that has not become apparently futile seems logical, yet the presence of certain factors may suggest a worse outcome.

Snail Mucus Enhances Chemosensitivity of Triple-negative Breast Cancer Via Activation of the Fas Pathway.

BACKGROUND/AIM: The poor prognosis and chemoresistance of patients with triple-negative breast cancer (TNBC) urge the development of new therapeutic strategies. Snail mucus has shown its ability against inflammation, a process closely related to tumorigenesis, suggesting a potential anti-cancer activity. MATERIALS AND METHODS: The effect and mechanisms of snail mucus on cell viability were determined by IncuCyte Live-cell analysis and molecular biological methods. The anti-cancer fractions of snail mucus were isolated and identified by medium pressure liquid chromatography (MPLC) and nuclear magnetic resonance (NMR) spectrometry analysis. RESULTS: Snail mucus significantly decreased the viability of TNBC cells with relatively lower cytotoxicity to normal breast epithelial cells and enhanced their response to chemotherapy through activation of Fas signaling by suppressing nucleolin. Two peptide fractions have been identified as the anti-cancer ingredients of the snail mucus. CONCLUSION: Snail mucus can induce programmed cell death via the extrinsic apoptotic pathway and has therapeutic potential by achieving a chemo-sensitizing effect in TNBCs.

Successful Surgical Salvage for a Patient with Ruptured Coronary Sinus during Percutaneous Ablation for Atrial Fibrillation: A Case Report.

Herein, we describe the rare anatomy of an abnormal shunt from the left atrium to the coronary sinus, which ruptured during a percutaneous ablation for atrial fibrillation. The iatrogenic lesion was successfully repaired after emergent extracorporeal membrane oxygenation set up followed by surgical exploration. The patient's postoperative course was uneventful, and she was regularly followed up without any complications.

Noninvasive and real-time in vivo characterization of Inflammation skin. A feasibility of animal study.

BACKGROUND: Inflammatory skin diseases were the most common problem in dermatology. This study aimed to develop a circuit by using a simple method for noninvasive, objective, and real-time skin inflammation screening. MATERIALS AND METHODS: Sprague-Dawley rats were used in this study. The rats were chemically induced to suffer from skin inflammation at the back of their left-hand side while the right-hand side of their back remained untreated serving as a control. Impedance (Z) spectrum of the rat's skin was recorded. RESULTS: Two characteristic frequencies (4.5 and 48.3 kHz) were found. At the two frequencies, the impedance of inflammatory skin tissue (ZIST ) was found to be significantly (P < .05) smaller than that of normal healthy skin tissue (ZNHST ). Moreover, the ratio of the impedance measured at 4.5 kHz (Zf = 4 .5 kHz ) to the impedance measured at 48.3 kHz (Zf = 48.3 kHz ), that is, Zf = 4.5 kHz /Zf = 48.3 kHz , was capable of skin inflammation screening. It was observed that the inflammatory skin tissue (IST) had the smaller value of Zf = 4 .5 kHz /Zf = 48.3 kHz (value < 8.5) and normal healthy skin tissue (NHST) had the higher value of Zf = 4 .5 kHz /Zf = 48.3 kHz (value ≈ 10) which almost remained constant. CONCLUSION: A circuit was developed which was used for measuring the skin impedance accurately at the two characteristic frequencies for skin inflammation screening.