Role of ursolic acid in preventing gastrointestinal cancer: recent trends and future perspectives.

Gastrointestinal malignancies are one of the major worldwide health concerns. In the present review, we have assessed the plausible therapeutic implication of Ursolic Acid (UA) against gastrointestinal cancer. By modulating several signaling pathways critical in cancer development, UA could offer anti-inflammatory, anti-proliferative, and anti-metastatic properties. However, being of low oral bioavailability and poor permeability, its clinical value is restricted. To deliver and protect the drug, liposomes and polymer micelles are two UA nanoformulations that can effectively increase medicine stability. The use of UA for treating cancers is safe and appropriate with low toxicity characteristics and a predictable pharmacokinetic profile. Although the bioavailability of UA is limited, its nanoformulations could emerge as an alternative to enhance its efficacy in treating GI cancers. Further optimization and validation in the clinical trials are necessary. The combination of molecular profiling with nanoparticle-based drug delivery technologies holds the potential for bringing UA to maximum efficacy, looking for good prospects with GI cancer treatment.

Pigmented skin exhibits accelerated wound healing compared to the nonpigmented skin in Guinea pig model.

This study investigated and compared the wound healing kinetics of pigmented (PG) and non-pigmented (NP) skin in guinea pigs, focusing on histological and transcriptional changes. Full-thickness wounds created on PG and NP skin were evaluated at various time points post-injury. Fontana-Masson staining and ultrastructural analysis suggested the presence of melanin and melanosomes in PG skin, which coincided with an upregulation of melanogenic genes cKIT, TYR, and DCT. On day 9 post-wound, PG skin exhibited a rapid transition from the inflammatory to proliferative phase, which correlated with the reappearance of epidermal pigmentation whereas the NP skin exhibited a delayed neo-epidermis formation. Furthermore, the study revealed that melanocyte-derived growth factors (conditioned media) positively regulated keratinocyte migration while inhibiting fibroblast differentiation. These effects were more prominent in tyrosine-treated (hyperpigmented) melanocyte-CM as was TGF- ß expression. These findings provide valuable insights into the mechanisms underlying skin repair and pigmentation.

Enhanced recovery programme after colorectal surgery in high-income and low-middle income countries: a systematic review and meta-analysis.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols strive to optimise outcomes following elective surgery; however, there is a dearth of evidence to support its equitable application and efficacy internationally. MATERIALS AND METHODS: The authors performed a systematic review and meta-analysis of studies on the uptake and impact of ERAS with the aim of highlighting differences in implementation and outcomes across high-income countries (HICs) and low-middle income countries (LMICs). The primary outcome was characterisation of global ERAS uptake. Secondary outcomes included length of hospital stay (LOS), 30-day readmission, 30-day mortality and postoperative complications. RESULTS: Three hundred thirty-seven studies with considerable heterogeneity were included in the analysis (291 from HICs, and 46 from LMICs) with a total of 110 190 patients. The weighted median number of implemented elements were similar between HICs and LMICs ( P =0·94), but there was a trend towards greater uptake of less affordable elements across all aspects of the ERAS pathway in HICs. The mean LOS was significantly shorter in patient cohorts in HICs (5·85 days versus 7·17 days in LMICs, P <0·001). The 30-day readmission rate was higher in HICs (8·5 vs. 4·25% in LMICs, P <0·001, but no overall world-wide effect when ERAS compared to controls (OR 1·00, 95% CI: 0·88-1·13). There were no reported differences in complications ( P =0·229) or 30-day mortality ( P =0·949). CONCLUSION: Considerable variation in the structure, the implementation and outcomes of ERAS exists between HICs and LMICs, where affordable elements are implemented, contributing towards longer LOS in LMICs. Global efforts are required to ensure equitable access, effective ERAS implementation and a higher standard of perioperative care world-wide.

Genome-wide profiling reveals pervasive transcriptional alterations in fibroblasts derived from lesional skin in vitiligo including a reduced potential to proliferate.

Fibroblasts interact with keratinocytes and melanocytes to maintain skin homeostasis. However, the impact of selective melanocyte loss on the transcriptome of fibroblasts is not fully understood. Thus, we sought to understand the genome-wide transcriptome of fibroblasts derived from non-lesional (NL) and lesional (L) dermis in patients with non-segmental vitiligo. Transcriptional profiling of NL and L fibroblasts was performed on three individuals with vitiligo using next-generation-sequencing. Functional protein-protein interaction (PPI) networks were constructed for the significantly upregulated and downregulated genes, as well as for a common set of genes that were downregulated in both fibroblasts and epidermis in L skin (identified previously). Proliferation potential of NL and L fibroblasts was assessed experimentally. Genome-wide transcriptome analysis revealed a total of 414 (282, downregulated; 132, upregulated) differentially expressed (DE)-transcripts in L as compared to NL fibroblasts. Unsupervised hierarchical clustering of DE-transcripts segregated L and NL fibroblasts into two distinct clades, despite the apparent heterogeneity in lesions of different vitiligo patients. Gene Ontology analysis of downregulated genes revealed enrichment of keratinocyte-specific biological processes such as cornification and keratinization. PPI networks constructed for the downregulated and upregulated genes revealed deregulation of several hub genes associated with cell cycle regulation and cAMP metabolism respectively. Similarly, the PPI networks constructed for 67 genes downregulated in both fibroblasts as well as epidermis of L skin revealed downregulation of hub genes including stratifin, PIK3CG and CDH1. Analysis of the in vitro proliferation potential of L fibroblasts revealed a decrease in the expression of proliferation markers Ki67, MCM6, pERK and pCDK2, a decreased S phase population and an increase in alpha-SMA and collagen expression, corroborating the downregulation of hub genes associated with proliferation identified by PPI network analysis. Our study revealed pervasive transcriptional alterations in L compared to NL fibroblasts in vitiligo. The PPI analysis suggested a reduced potential to proliferate in melanocyte-deprived lesional fibroblasts, which was validated experimentally as well.

Safety and effectiveness of live broadcast of surgical procedures: systematic review.

INTRODUCTION: Live Broadcast of Surgical Procedures (LBSP) has gained popularity in conferences and educational meetings in the past few decades. This is due to rapid advancement in both Minimally Invasive Surgery (MIS) that enable transmission of the entire operative field and transmission ease and technology to help broadcast the operation to a live audience. The aim of this study was to update the evidence with specific emphasis on the patient safety issues related to LBSP in MIS. METHODS: A systematic review of the literature was performed using Medline, Embase and Pubmed using defined search terms related to LBSP in educational events across all surgical specialities, in accordance with the PRISMA guidelines. We also consolidated the prior guidelines and position statements on this topic. Outcomes included reports on the educational value of LBSP as well as patient safety outcomes and ethical issues that were captured by clinical outcomes. RESULTS: A total 1230 abstracts were identified with 27 papers meeting the inclusion criteria (13 original articles and 14 position statements/guidelines). All studies highlighted the educational benefits of LBSP but without clear measure of these benefits. Clinical outcomes were not compromised in 9 studies but were inferior in the remaining 4, including lower completion rate of endoscopic surgery and higher rate of re-operation. Only nine studies complied with dedicated consent forms for LBSP with no consistent approach of reporting on maintaining patient confidentiality during LBSP. There was a lack of recommendation on standardised approach of reporting on LBSP including the outcomes across the 14 published guidelines and positions statements. CONCLUSIONS: Live Broadcast of Surgical Procedures can be of educational value but patient safety may be compromised. A standardised framework of reporting on LBSP and its outcomes is required from an ethical and patient safety perspective. PROSPERO REGISTRATION: CRD42021256901.

Integrated analysis of miRNA-mRNA networks reveals a strong anti-skin cancer signature in vitiligo epidermis.

Expression of microRNAs (miRNAs) is often dysregulated in several cancers, including non-melanoma skin cancer (NMSC). Individuals with vitiligo possess a deregulated miRnome along with a lower risk of developing NMSCs. We used data sets from our previously published studies on vitiligo epidermis to construct functional miRNA-mRNA networks to understand the molecular basis underlying the lower incidence of NMSC observed in individuals with vitiligo. miRTarBase database was used to fetch the experimentally validated targets of differentially expressed miRNAs and two protein-protein interaction (PPI) networks were constructed for the miRNA-mRNA interactions (230 downregulated targets of 5 upregulated miRNAs and 47 upregulated mRNAs targeted by 12 downregulated miRNAs). Pathway enrichment analysis identified RNA biogenesis and transport as well as cell adhesion to be perturbed in vitiligo. Further, oncogenic transcription factors (OTFs) that were upregulated in publicly available squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) microarray data were compared with that of vitiligo to decode skin cancer-specific molecular signatures. We identified three significantly upregulated miRNAs, miR-31-5p, miR-31-3p and miR-194-3p in lesional epidermis that could negatively regulate seven oncogenic transcription factors, FOXC1, AR, SP1, YY1, GLI2, TP53 and RARA, known to be over-expressed in SCC or BCC. Taken together, our study identified a perturbed miRNA-regulated transcriptome, which potentially confers protection to vitiligo skin from an increased incidence of NMSC.

Impact and outcomes of postoperative anaemia in colorectal cancer patients: a systematic review.

AIM: Preoperative anaemia is common in colorectal cancer patients. Little attention has been given to the prevalence and consequences of postoperative anaemia. The aim of this study was to systematically review the published literature and determine the knowledge of the prevalence and impact of postoperative anaemia in colorectal cancer patients. METHODS: The databases Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Medline, via EBSCOhost, were systematically searched to identify suitable articles published between 2004 and 2020. After an initial search, articles were screened and all eligible articles reporting on the prevalence of postoperative anaemia and clinical and long-term outcome data in colorectal cancer patients undergoing surgery were included. The Risk of Bias 2.0 tool for the assessment of randomized controlled trials and the Risk of Bias 1.0 tool for non-randomized studies were used for the assessment of bias in the studies selected in our review. RESULTS: Six studies, one randomized control trial and five cohort studies, were included with a total population size of 1714. The prevalence of anaemia at discharge of 76.6% was reported as the primary end-point in only one study. The rate of red blood cell transfusion and length of hospital stay were found to be significantly increased in anaemic patients, while postoperative infection rate results were variable. Quality of life scores and overall survival at 5 years were significantly affected among anaemic patients as reported in two papers. CONCLUSION: The available limited evidence on postoperative anaemia indicates its high prevalence with negative impact on clinical and long-term outcomes. Further research is required to standardize the measurement and address the true impact of correcting postoperative anaemia on functional and oncological outcomes.

The risk of fatal re-expansion pulmonary oedema in poor left ventricular reserve.

Re-expansion pulmonary oedema (REPO) is an uncommon complication which may be encountered following drainage of pneumothorax, pleural effusion or haemopneumothorax. Treatment is usually supportive and some patients may require positive pressure ventilation. We provide a novel description of the mechanism of a fatal REPO in a patient with a small and non-compliant left ventricle (LV). We urge for an extreme caution when performing thoracocentesis in patients with poor LV reserve.

Mediastinal irradiation and its effect on the cardiovascular system.

Mediastinal irradiation for various malignancies can cause radiation injury to mediastinal structures, most importantly the cardiovascular system. This article reviews the effect of radiation on cardiovascular structures and the manifestations of various radiation-induced heart diseases.