Medulla Tetrapanacis water extract alleviates inflammation and infection by regulating macrophage polarization through MAPK signaling pathway.

Medulla Tetrapanacis (MT) is a commonly used herb to promote lactation and manage mastitis in lactating mothers. However, its anti-inflammatory and anti-bacterial effects are currently unknown. We hypothesized that MT water extract possesses anti-inflammatory and anti-bacterial effects by modulating macrophage polarization to reduce the release of inflammatory mediators and phagocytosis via inactivation of MAPKs pathways. The chemical composition of the MT water extract was analyzed by UPLC-Orbitrap-mass spectrometry. The anti-inflammatory and anti-bacterial properties of the MT water extract were examined using LPS-stimulated inflammation and Staphylococcus aureus infection model in RAW 264.7 cells, respectively. The underlying mechanism of action of the MT water extract was also investigated. We identified eight compounds by UPLC-Orbitrap-mass spectrometry that are abundant within the MT water extract. MT water extract significantly suppressed LPS-induced nitric oxide, TNF-α and IL-6 secretion in RAW 264.7 cells which was accompanied by the promotion of macrophage polarization from pro-inflammatory towards anti-inflammatory phenotypes. MT water extract significantly suppressed the LPS-induced MAPK activation. Finally, MT water extract decreased the phagocytic capacity of the RAW 264.7 cells against S. aureus infection. MT water extract could suppress LPS-induced inflammation by promoting macrophages towards an anti-inflammatory phenotype. In addition, MT also inhibited the growth of S. aureus.

The Utility of Ultrasound Guidance to Improve the Safety of Closure of Antegrade Common Femoral Artery Access after Lower Limb Revascularization.

This study aimed to investigate the feasibility of ultrasound (US)-guidance in reducing adverse event (AE) rates when using Angioseal device during antegrade lower limb angioplasty via common femoral artery access. From December 2016 to November 2022, 1,322 patients were identified, including 1,131 (85.6%) patients who underwent US-guided closure and 191 (14.4%) who underwent non-US-guided closure. Moderate AEs were encountered in 10 (5.2%) patients in the non-US-guided closure group compared to 38 (3.4%) patients in the US-guided closure group (P = .208). Severe AEs were encountered in 4 (2.1%) patients in the non-US-guided closure group compared to 3 (0.3%) patients in the US-guided closure group (P = .010). Overall AEs occurred in 14 (7.3%) patients in the non-US-guided closure group compared to 41 (3.6%) patients in the US-guided closure group (P = .029). Binary logistic regression showed that only non-US guidance was an independent risk factor for the occurrence of severe AEs (P = .008).

An Update of Lectins from Marine Organisms: Characterization, Extraction Methodology, and Potential Biofunctional Applications.

Lectins are a unique group of nonimmune carbohydrate-binding proteins or glycoproteins that exhibit specific and reversible carbohydrate-binding activity in a non-catalytic manner. Lectins have diverse sources and are classified according to their origins, such as plant lectins, animal lectins, and fish lectins. Marine organisms including fish, crustaceans, and mollusks produce a myriad of lectins, including rhamnose binding lectins (RBL), fucose-binding lectins (FTL), mannose-binding lectin, galectins, galactose binding lectins, and C-type lectins. The widely used method of extracting lectins from marine samples is a simple two-step process employing a polar salt solution and purification by column chromatography. Lectins exert several immunomodulatory functions, including pathogen recognition, inflammatory reactions, participating in various hemocyte functions (e.g., agglutination), phagocytic reactions, among others. Lectins can also control cell proliferation, protein folding, RNA splicing, and trafficking of molecules. Due to their reported biological and pharmaceutical activities, lectins have attracted the attention of scientists and industries (i.e., food, biomedical, and pharmaceutical industries). Therefore, this review aims to update current information on lectins from marine organisms, their characterization, extraction, and biofunctionalities.

Conservative Management of Obesity in Kidney Transplant Candidates.

OBJECTIVE: Obesity is prevalent in patients with chronic kidney disease and is associated with increased complications after kidney transplantation (KT). A body mass index limit is used in most transplant programs, though few studies have focused on conservative weight loss in KT candidates. The objective of this retrospective study is to evaluate the efficacy of a basic conservative weight management program in morbidly obese KT candidates and to perform a comprehensive nutritional evaluation. METHODS: This retrospective study included patients with a body mass index (BMI) >35 kg/m2, with grade IV or V chronic kidney disease. The conservative weight loss program consisted of anthropometric measurements every 3 months, consultation with a nutritionist, daily exercise, and counseling for healthier eating habits. Overall and quarterly BMI targets were defined. A subset of patients further underwent a comprehensive nutritional evaluation to measure socioeconomic characteristics, food intake behavior, motivation for change, and a 4-day food diary. RESULTS: Eighty patients were observed for a mean of 24 months. Successful weight loss (BMI < 35 kg/m2) was achieved in 26.3%, associated with women and those already close to the limit. The mean 1-year excess body weight loss was 8.4%. No patient with a BMI >40 kg/m2 was successful. The comprehensive nutritional evaluation was performed with 44 patients and found that only 14.6% had previously received nutritional counseling for weight loss. Cognitive restraint scored highest in the food-intake behavior. Most patients were motivated to lose weight with 66% in the action phase. There was little evidence of overeating with a recommended mean calculated daily caloric intake of 82.9%. CONCLUSION: The conservative weight loss program can have limited but non-negligible, success. Future successful nutritional interventions should take into consideration this surprising comprehensive profile of morbidly obese KT candidates.

Successful surgical weight loss with laparoscopic sleeve gastrectomy for morbid obesity prior to kidney transplantation.

Morbid obesity in kidney transplant (KT) candidates is associated with increased complications and graft failure. Multiple series have demonstrated rapid and significant weight loss after laparoscopic sleeve gastrectomy (LSG) in this population. Long-term and post-transplant weight evolutions are still largely unknown. A retrospective review was performed in eighty patients with end-stage kidney disease (ESKD) who underwent LSG in preparation for KT. From a median initial BMI of 43.7 kg/m2 , the median change at 1-year was -10.0 kg/m2 . Successful surgical weight loss (achieving a BMI < 35 kg/m2 or an excess body weight loss >50%) was attained in 76.3% and was associated with male gender, predialysis status, lower obesity class and lack of coronary artery disease. Thirty-one patients subsequently received a KT with a median delay of 16.7 months. Weight regain (increase in BMI of 5 kg/m2 postnadir) and recurrent obesity (weight regain + BMI > 35) remain a concern, occurring post-KT in 35.7% and 17.9%, respectively. Early LSG should be considered for morbidly obese patients with ESKD for improved weight loss outcomes. Early KT after LSG does not appear to affect short-term surgical weight loss. Candidates with a BMI of up to 45 kg/m2 can have a reasonable expectation to achieve the limit within 1 year.

Prospective study of the changes in pharmacokinetics of immunosuppressive medications after laparoscopic sleeve gastrectomy.

Laparoscopic sleeve gastrectomy induces weight loss via the creation of a restrictive gastric tube for early satiety and is associated with an accelerated gastric transit time. A prospective, single-dose pharmacokinetic study was performed, prior to and after laparoscopic sleeve gastrectomy, for tacrolimus, extended-release tacrolimus, mycophenolate mofetil, and enteric-coated mycophenolate sodium. The study included 12 morbidly obese patients in chronic renal failure. The median decrease in body mass index was 8.8 kg/m2 with an excess body weight loss of 54.9%. The AUC24 of all drugs were increased after laparoscopic sleeve gastrectomy by 46%, 55%, 77%, and 74%, respectively. The maximum concentrations were increased for tacrolimus, extended-release tacrolimus, and mycophenolate mofetil by 43%, 46%, and 65%. The apparent total clearances were decreased for tacrolimus, mycophenolate mofetil, and enteric-coated mycophenolate sodium by 36%, 57%, and 38%. Laparoscopic sleeve gastrectomy can be associated with significant changes in pharmacokinetics of the drugs evaluated. The mechanism is likely decreased apparent drug clearance due to an increased drug exposure (from a more distal site of intestinal absorption with decreased intestinal metabolism), or decreased clearance (liver metabolism). Adapting the monitoring of immunosuppression will be important to avoid overdosing and potential side effects.

Identification of master regulator genes of UV response and their implications for skin carcinogenesis.

Solar UV radiation is a major environmental risk factor for skin cancer. Despite decades of robust and meritorious investigation, our understanding of the mechanisms underlying UV-induced skin carcinogenesis remain incomplete. We previously performed comprehensive transcriptomic profiling in human keratinocytes following exposure to different UV radiation conditions to generate UV-specific gene expression signatures. In this study, we utilized Virtual Inference of Protein Activity by Enriched Regulon (VIPER), a robust systems biology tool, on UV-specific skin cell gene signatures to identify master regulators (MRs) of UV-induced transcriptomic changes. We identified multiple prominent candidate UV MRs, including forkhead box M1 (FOXM1), thyroid hormone receptor interactor 13 and DNA isomerase II alpha, which play important roles in cell cycle regulation and genome stability. MR protein activity was either activated or suppressed by UV in normal keratinocytes. Intriguingly, many of the UV-suppressed MRs were activated in human skin squamous cell carcinomas (SCCs), highlighting their importance in skin cancer development. We further demonstrated that selective inhibition of FOXM1, whose activity was elevated in SCC cells, was detrimental to SCC cell survival. Taken together, our study uncovered novel UV MRs that can be explored as new therapeutic targets for future skin cancer treatment.

Making technological innovation work for sustainable development.

This paper presents insights and action proposals to better harness technological innovation for sustainable development. We begin with three key insights from scholarship and practice. First, technological innovation processes do not follow a set sequence but rather emerge from complex adaptive systems involving many actors and institutions operating simultaneously from local to global scales. Barriers arise at all stages of innovation, from the invention of a technology through its selection, production, adaptation, adoption, and retirement. Second, learning from past efforts to mobilize innovation for sustainable development can be greatly improved through structured cross-sectoral comparisons that recognize the socio-technical nature of innovation systems. Third, current institutions (rules, norms, and incentives) shaping technological innovation are often not aligned toward the goals of sustainable development because impoverished, marginalized, and unborn populations too often lack the economic and political power to shape innovation systems to meet their needs. However, these institutions can be reformed, and many actors have the power to do so through research, advocacy, training, convening, policymaking, and financing. We conclude with three practice-oriented recommendations to further realize the potential of innovation for sustainable development: (i) channels for regularized learning across domains of practice should be established; (ii) measures that systematically take into account the interests of underserved populations throughout the innovation process should be developed; and (iii) institutions should be reformed to reorient innovation systems toward sustainable development and ensure that all innovation stages and scales are considered at the outset.

Vascular control during laparoscopic kidney donation.

SUMMARY: Laparoscopic donor nephrectomy (LDN) is the gold standard for kidney donation. Recent literature has led to considerable debate regarding the safest route to provide vascular control during this procedure. The most common devices used for vascular control during LDN are staplers and surgical clips. Opinions regarding the safety of these devices vary, as both are prone to dysfunction. Certain clips have already been contraindicated for use on the donor artery owing to reports of catastrophic complications of falling off. Donor safety is paramount to the continued success of renal transplantation in Canada. A review of existing practice at each institution may be called for to ensure the safest standards possible are in place. An appendix to this commentary is available at canjsurg.ca.

An immunoassay system to investigate epidemiology of Rocahepevirus ratti (rat hepatitis E virus) infection in humans.

Background & Aims: Rat hepatitis E virus (Rocahepevirus ratti; HEV-C1) is an emerging cause of hepatitis E that is divergent from conventional human-infecting HEV variants (Paslahepevirus balayani; HEV-A). Validated serological assays for HEV-C1 are lacking. We aimed to develop a parallel enzymatic immunoassay (EIA) system that identifies individuals with HEV-C1 exposure. We also aimed to conduct the first HEV-C1 seroprevalence study in humans using this validated EIA system. Methods: Expressed HEV-A (HEV-A4 p239) and HEV-C1 (HEV-C1 p241) peptides were characterised. Blood samples were simultaneously tested in HEV-A4 p239 and HEV-C1 p241 IgG EIAs. An optical density (OD) cut-off-based interpretation algorithm for identifying samples seropositive for HEV-A or HEV-C1 was validated using RT-PCR-positive infection sera. This algorithm was used to measure HEV-C1 seroprevalence in 599 solid organ transplant recipients and 599 age-matched immunocompetent individuals. Results: Both peptides formed virus-like particles. When run in HEV-A4 p239 and HEV-C1 p241 EIAs, HEV-A and HEV-C1 RT-PCR-positive samples formed distinct clusters with minimal overlap in a two-dimensional plot of optical density values. The final EIA interpretation algorithm showed high agreement with RT-PCR results (Cohen's κ = 0.959) and was able to differentiate HEV-A and HEV-C1 infection sera with an accuracy of 94.2% (95% CI: 85.8-98.4%). HEV-C1 IgG seroprevalence was 7/599 (1.2%) among solid organ transplant recipients and 4/599 (0.7%) among immunocompetent individuals. Five of 11 (45.5%) of these patients had history of transient hepatitis of unknown cause. Conclusions: HEV-C1 exposure was identified in 11/1198 (0.92%) individuals in Hong Kong indicating endemic exposure. This is the first estimate of HEV-C1 seroprevalence in humans. The parallel IgG EIA algorithm is a valuable tool for investigating epidemiology and risk factors for HEV-C1 infection. Impact and Implications: Rat hepatitis E virus has recently been discovered to infect humans, but antibody tests for this infection are lacking, making it difficult to gauge how common this infection is. We developed an antibody test algorithm that can identify individuals with past rat hepatitis E virus exposure. We used this algorithm to estimate rat hepatitis E exposure rates in humans in Hong Kong and found that approximately 1% of all tested people had been exposed to this virus previously.

An emerging role for the nuclear localization of maspin in the suppression of tumor progression and metastasis.

Maspin, a member of the serpin family of serine protease inhibitors, was originally identified as a tumor suppressor that is expressed in normal mammary epithelial cells but is reduced or absent in breast carcinomas. Early enthusiasm for maspin as a biomarker for disease progression has been tempered by clinical data that associates maspin with favourable outcomes in some studies and poor prognosis in others. Here, we review all of the published clinical studies for maspin in breast and ovarian cancers and propose that the apparent discordance between clinical reports is a consequence of differential cellular distribution of maspin. Indeed, it was thought that an extracellular pool of maspin possessed tumor suppressor activity, acting by inhibiting migration and increasing cell adhesion. Recent evidence from our group and others indicates, however, that the nuclear localization of maspin in cancer cells is necessary for its tumor suppressor activity. We provide additional data here to demonstrate that nuclear-localized maspin binds to chromatin and is required to effectively prevent cells from metastasizing. Our knowledge of other serpins that localize to the nucleus should help to inform future studies of nuclear maspin. Elucidation of the molecular mechanisms regulating the localization and activities of maspin should pave the way for the development of improved diagnostics and therapies for cancer.

The role of p53 in the alternation of vascular functions.

Ageing is a risk factor for many degenerative diseases. Cardiovascular diseases (CVDs) are usually big burdens for elderly, caregivers and the health system. During the aging process, normal functions of vascular cells and tissue progressively lost and eventually develop vascular diseases. Endothelial dysfunction, reduced bioavailability of endothelium-derived nitric oxide are usual phenomena observed in patients with cardiovascular diseases. Myriad of studies have been done to investigate to delay the vascular dysfunction or improve the vascular function to prolong the aging process. Tumor suppressor gene p53, also a transcription factor, act as a gatekeeper to regulate a number of genes to maintain normal cell function including but not limited to cell proliferation, cell apoptosis. p53 also crosstalk with other key transcription factors like hypoxia-inducible factor 1 alpha that contribute to the progression of cardiovascular diseases. Therefore, in recent three decades, p53 has drawn scientists' attention on its effects in vascular function. Though the role of tumor suppressor gene p53 is still not clear in vascular function, it is found to play regulatory roles and may involve in vascular remodeling, atherosclerosis or pulmonary hypertension. p53 may have a divergent role in endothelial and vascular muscle cells in those conditions. In this review, we describe the different effects of p53 in cardiovascular physiology. Further studies on the effects of endothelial cell-specific p53 deficiency on atherosclerotic plaque formation in common animal models are required before the therapeutic potential can be realized.

Association of preoperative parameters with postoperative mortality and long-term survival after liver transplantation.

BACKGROUND: The ability of Child-Turcotte-Pugh (CTP) or Model for End-Stage Liver Disease (MELD) scores to predict recipient survival after liver transplantation is controversial. This analysis aims to identify preoperative parameters that might be associated with early postoperative mortality and long-term survival after liver transplantation. METHODS: We studied a total of 15 parameters, using both univariate and multivariate models, among adults who underwent primary liver transplantation. RESULTS: A total of 458 primary adult liver transplants were performed. Fifty-seven (12.44%) patients died during the first 3 postoperative months and composed the early mortality group. The remaining 401 patients composed the long-term patient survival group. The parameters that were identified through univariate analysis to be associated with early postoperative mortality were CTP score, MELD score, bilirubin, creatinine, international normalized ratio and warm ischemia time (WIT). In all multivariate models, WIT retained its statistical significance. The 10-year long-term survival was 65%. The parameters that were identified to be independent predictors of long-term survival were the recipient's sex (improved survival in women, p = 0.005), diagnosis of hepatocellular cancer (p=0.015) and recipient's age (p=0.024). CONCLUSION: Either CTP or MELD score, in conjunction with WIT, might have a role in predicting early postoperative mortality after liver transplantation, whereas the recipient's sex and the absence of hepatocellular cancer are associated with improved long-term survival.

Combined Biopsy and Imaging-Guided Microwave Ablation by Using a Coaxial Guiding Needle.

This article demonstrates the technique of using a coaxial guiding needle to perform combined percutaneous biopsy and microwave ablation via a single tract. From May 2019 to July 2020, 14 patients underwent combined biopsy and microwave ablation by using a coaxial guiding cannula. Tumors were in the kidney of six patients (43%), the liver of six patients (43%), and the lung in two patients (14%). The diagnostic yield of biopsy was 86% (12/14). Ablation technical success rate was 100%. In conclusion, using a coaxial guiding needle in microwave ablation and biopsy is safe and effective.

Single-Setting Superior Vena Cava Biopsy and Stenting Utilizing Cone Beam Computed Tomography as an Additional Tool.

BACKGROUND Malignant disease is a common etiology of superior vena cava syndrome (SVCS). Being a medical emergency, it often requires rapid diagnostic evaluation and therapy. Transcaval biopsy and endovascular stenting in a single-setting has been described, but only in a handful of cases. These cases utilized intra-operative venograms. In this study, we also used intra-operative cone beam computed tomography (CBCT) to increase the safety and efficacy of such single-setting procedures. CASE REPORT From January 2017 to July 2019, there were 5 patients with malignant SVCS who underwent single-setting superior vena cava biopsy and endovascular stenting utilizing intra-operative CBCT as an adjunct. Demographic data, clinical presentation, investigation results, procedural details, and patient outcomes were recorded. CBCT was utilized in all cases to optimize sampling of biopsies, visualize subsequent stent positioning, and for early detection of procedure-related complications. Transcaval biopsy was diagnostic in 4 of the 5 patients. Endovascular stents were deployed successfully in all cases, with post-stenting venogram demonstrating relief of prior obstructed segments. One patient had a complication of an apical pneumothorax, with no associated long-term pneumothorax-related morbidity or mortality. CONCLUSIONS This study demonstrates that single-setting transcaval biopsy and stenting in the context of malignant SVCS is a cost-efficient, safe, and feasible approach. In addition, the additional use of intra-operative CBCT is a useful tool to increase procedure efficacy and safety.

Pathological response grade of colorectal liver metastases treated with neoadjuvant chemotherapy.

BACKGROUND: The complete resection of liver metastases from colorectal cancer is the major determinant of longterm survival. The effectiveness of current chemotherapy regimens has made treatment algorithms more flexible and resulted in many different options. Recently, the pathological response to chemotherapy has emerged as another important prognostic marker. Different systems have been used to grade the pathological response in these patients. METHODS: This study prospectively evaluates the prognostic value of the pathological response grade (PRG) in liver metastases treated with neoadjuvant chemotherapy. RESULTS: Between 2002 and 2006, 50 patients were treated with a sandwich chemotherapy regimen and underwent liver resection. Complete resection was achieved in 45 patients (90%). A strong pathological response to chemotherapy (<10% viable tumour cells in all lesions) was seen in 17 patients (34%). It was associated with a statistically significant longer overall survival (P= 0.019) and was also identified on multivariate analysis as an independent predictor of survival (odds ratio = 243). CONCLUSIONS: This pilot study demonstrates the prognostic potential of the PRG, which could be used clinically to select patients for an aggressive multimodal adjuvant algorithm. Larger multicentre studies are required to validate this particular grading system. The keys to longterm survival are resectability and chemo-responsiveness.

Solar photovoltaic interventions have reduced rural poverty in China.

Since 2013, China has implemented a large-scale initiative to systematically deploy solar photovoltaic (PV) projects to alleviate poverty in rural areas. To provide new understanding of China's targeted poverty alleviation strategy, we use a panel dataset of 211 pilot counties that received targeted PV investments from 2013 to 2016, and find that the PV poverty alleviation pilot policy increases per-capita disposable income in a county by approximately 7%-8%. The effect of PV investment is positive and significant in the year of policy implementation and the effect is more than twice as high in the subsequent two to three years. The PV poverty alleviation effect is stronger in poorer regions, particularly in Eastern China. Our results are robust to alternative specifications and variable definitions. We propose several policy recommendations to sustain progress in China's efforts to deploy PV for poverty alleviation.