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.

Cigarette smoke-induced LKB1/AMPK pathway deficiency reduces EGFR TKI sensitivity in NSCLC.

Smoker patients with non-small cell lung cancer (NSCLC) have poorer prognosis and survival than those without smoking history. However, the mechanisms underlying the low response rate of those patients to EGFR tyrosine kinase inhibitors (TKIs) are not well understood. Here we report that exposure to cigarette smoke extract enhances glycolysis and attenuates AMP-activated protein kinase (AMPK)-dependent inhibition of mTOR; this in turn reduces the sensitivity of NSCLC cells with wild-type EGFR (EGFRWT) to EGFR TKI by repressing expression of liver kinase B1 (LKB1), a master kinase of the AMPK subfamily, via CpG island methylation. In addition, LKB1 expression is correlated positively with sensitivity to TKI in patients with NSCLC. Moreover, combined treatment of EGFR TKI with AMPK activators synergistically increases EGFR TKI sensitivity. Collectively, the current study suggests that LKB1 may serve as a marker to predict EGFR TKI sensitivity in smokers with NSCLC carrying EGFRWT and that the combination of EGFR TKI and AMPK activator may be a potentially effective therapeutic strategy against NSCLC with EGFRWT.

Transdermal Delivery Systems of Natural Products Applied to Skin Therapy and Care.

Natural products are favored because of their non-toxicity, low irritants, and market reacceptance. We collected examples, according to ancient wisdom, of natural products to be applied in transdermal delivery. A transdermal delivery system, including different types of agents, such as ointments, patches, and gels, has long been used for skin concerns. In recent years, many novel transdermal applications, such as nanoemulsions, liposomes, lipid nanoparticles, and microneedles, have been reported. Nanosized drug delivery systems are widely applied in natural product deliveries. Nanosized materials notably enhance bioavailability and solubility, and are reported to improve the transdermal permeation of many substances compared with conventional topical formulations. Natural products have been made into nanosized biomaterials in order to enhance the penetration effect. Before introducing the novel transdermal applications of natural products, we present traditional methods within this article. The descriptions of novel transdermal applications are classified into three parts: liposomes, emulsions, and lipid nanoparticles. Each section describes cases that are related to promising natural product transdermal use. Finally, we summarize the outcomes of various studies on novel transdermal agents applied to skin treatments.

The curative effects of the traditional Chinese herbal medicine "Jinchuang ointment" on excisional wounds.

BACKGROUND: "Jinchuang ointment" is a traditional Chinese herbal medicine for external incised wounds. This herbal medicine has been successfully used to treat patients with diabetic foot ulcers and pressure sores in Taiwan for several decades. We previously examined its biological activities on cell-based in vitro assay platforms. Because some patients refused to use animal-derived ingredients ointment during our clinical practice, the efficacy of plant oil-based reconstituted "Jinchuang ointment" was also investigated. METHODS: A porcine excisional wound model was established and used to evaluate its efficacy in vivo in this study. Besides, an unusual clinical case is also present. RESULTS: As judged from the wound appearance of animal studies on day 14 and the results of blood flow flux at the wound sites on day 28, "Jinchuang ointment" accelerated wound closure significantly better than the control group. CONCLUSIONS: The results from clinical treatment, histopathological evaluation, and the animal study showed that "Jinchung ointment" promotes wound healing significantly better than the control group. Also, sesame oil-reconstituted ointment can be a choice for patients who refuse to use lard-containing ointment.

Intraoperative computed tomography-guided localization of nonpalpable rib tumor for tumor excision.

A nonpalpable rib tumor is very difficult to localize accurately, so a skin incision is also difficult to design. Many methods have been discussed but most of them have some disadvantages such as inaccurate localization, the need to create another incision and not being generally useful for most patients. We offer one method of intraoperative localization in the hybrid operative room (OR). In our experience, it took a short time and had great accuracy, thus we could minimize the skin incision.

Proteasome Inhibitors Suppress ErbB Family Expression through HSP90-Mediated Lysosomal Degradation.

Although dual EGFR/HER2 tyrosine kinase inhibitor lapatinib has provided effective clinical benefits for HER2-positive breast cancer patients, acquired resistance to this drug remains a major concern. Thus, the development of alternative therapeutic strategies is urgently needed for patients who failed lapatinib treatment. Proteasome inhibitors have been reported to possess high anti-tumor activity to breast cancer cells. Therefore, this study aims to examine whether and how proteasome inhibitor bortezomib can overcome lapatinib resistance. Treatments with several proteasome inhibitors, including Bortezomib, MG132, and proteasome inhibitor I (PSI), as well as the viabilities of both HER2-positive breast cancer cell lines and their lapatinib-resistant clones, were inhibited. Importantly, the expressions of ErbB family were downregulated at both transcriptional and translational levels. Also, our results further indicated that proteasome inhibitors decreased ErbB family expression through lysosomal degradation pathway in a heat shock protein 90 (HSP90)-dependent manner. In this study, our data supported a potential approach to overcome the acquired resistance of HER2-overexpressing breast cancer patients to lapatinib using proteasome inhibitors.

Idea and innovation: Secure fixation between dermis and periosteum using perforator flap to prevent recurrence of pilonidal sinus disease.

In the past decades, numerous surgical techniques and conservative treatments for pilonidal sinus disease (PSD) had been discussed and published. There is still no consensus yet of the best techniques because of high recurrence rates and prolonged wound healing. In the case of complicated discharging sinus or recurrent PSD resistant to treatment with antibiotics, we recommend radical excision followed by a regional flap, which can obliterate the dead space with well-vascularised tissue. In this article, we presented the technique of snug suture fixation between the dermis and periosteum using a superior gluteal artery perforator (SGAP) flap. The study demonstrates a few key concepts on the prevention of PSD recurrence, an off-midline, well-perfused flap that allows flattened natal cleft and obliteration of gluteal cleft and eventually showed good aesthetic results. We aim to demonstrate a reliable surgical technique for wound closure of recurrent pilonidal sinus after radical excision followed by reconstruction with an SGAP flap. The history, surgery, and images are described, and the literature is reviewed. The pitfalls of disease recurrence will be discussed in this literature. Keys to successful treatment will be elaborated. An 18-year-old female with recurrent pilonidal sinus disease over right medial gluteal region presented with sacral pain and infection. She developed progressive swelling and burst of abscess from several sinus tracts and did not respond to the treatment with antibiotics alone. After radical excision of the entire pilonidal sinus and adjacent fibrotic tissue, a deep and large defect was measured. A superior gluteal perforator flap was designed based on three perforators from the superior gluteal artery. A medial 3 cm of the SGAP flap was de-epithelised to provide soft tissue bulk to obliterate the deep cavity. Strong sutures were applied to secure the flap to the periosteum. There was no recurrence at 3 years of follow up. The patient stood the operation well and had prompt recovery.

The Application of Far-Infrared in the Treatment of Wound Healing: A Short Evidence-Based Analysis.

Far-infrared (FIR) radiation therapy has been used for soothing effect in wound treatment. Studies have shown that FIR could enhance wound healing processes in rat models. Although these research results supported that FIR may play an important for wound healing, it had no consensus in clinical practices. It is suggested that more persuasive systemic clinical researches are needed to explore the effectiveness of FIR therapy for wound healing.

The development and validation of an acne self-regulation inventory.

BACKGROUND: Acne, an inflammatory disease of the pilosebaceous unit, is now recognized and investigated as a chronic disease. Since the physiological and psychosocial impact of acne may be long-lasting, the treatment of acne vulgaris poses a formidable challenge for dermatologists. OBJECTIVE: The present study aims at investigating the validity and reliability of a self-developed instrument "acne self-regulation inventory" (ASRI) based on self-regulation theory in assessing the selfregulation ability of acne patients as part of the therapeutic strategy. METHODS: All proposed items to be included in ASRI, which consisted of four subscales (i.e., self-monitoring, self-judgment, self-reaction, and self-motivation), were first reviewed by 5 experts in the field. Pilot testing of scale reliability and validity of ASRI were then performed by recruiting 144 acne patients, followed by conduction of formal questionnaire survey by enrolling other 90 acne patients to complete a questionnaire comprising the refined ASRI, Cardiff Acne Disability Index (CADI), and Dermatology Life Quality Index (DLQI) to obtain constructive validity to evaluate the associations of ASRI with clinical acne grading scores, CADI, and DLQI. RESULTS: Expert review resulted in the inclusion of totally 31 items for pilot testing (i.e., self-monitoring 6 items, self-judgment 6 items, self-reaction 12 items, and self-motivation 7 items). The differentiating ability of each item was confirmed by significant difference between the higher third scorers and those of the lower third using t-test for independent means (all p<0.001). Moreover, Cronbach's α indicated that deletion of a single item in ASRI did not elevate mean value above 0.958 and removal of each item in the four subscales did not increase the mean value of the set Cronbach's α value for each subscale (i.e., 0.886; 0.860; 0.895; 0.907, respectively), suggesting suitability of the 31 items. A high Cronbach's α coefficient of the whole scale as well as the four subscales (i.e., 0.958; 0.886, 0.860, 0.895, and 0.907) demonstrated a high reliability of the ASRI. Pearson's correlation demonstrated moderate to high discriminant validity of ASRI with coefficients between each pair of the four subscales ranging from 0.637-0.798. Formal questionnaire survey demonstrated significant difference between the higher third ASRI scorers and those of the lower third in comparison with clinical acne grading scores, CADI, and DLQI, using t-test for independent means (both p=0.001). CONCLUSION: The results of the present study demonstrated the usefulness of a self-developed ASRI as an assessment tool to be included in the treatment strategy for acne patients.

The In Vitro and In Vivo Wound Healing Properties of the Chinese Herbal Medicine "Jinchuang Ointment".

"Jinchuang ointment" is a traditional Chinese herbal medicine complex for treatment of incised wounds. For more than ten years, it has been used at China Medical University Hospital (Taichung, Taiwan) for the treatment of diabetic foot infections and decubitus ulcers. Three different cases are presented in this study. "Jinchuang" ointment is a mixture of natural product complexes from nine different components, making it difficult to analyze its exact chemical compositions. To further characterize the herbal ingredients used in this study, the contents of reference standards present in a subset of the ointment ingredients (dragon's blood, catechu, frankincense, and myrrh) were determined by HPLC. Two in vitro cell based assay platforms, wound healing and tube formation, were used to examine the biological activity of this medicine. Our results show that this herbal medicine possesses strong activities including stimulation of angiogenesis, cell proliferation, and cell migration, which provide the scientific basis for its clinically observed curative effects on nonhealing diabetic wounds.