Short- and long-term cardiovascular outcomes in insulin-treated versus non-insulin-treated diabetes mellitus patients after percutaneous coronary intervention: A systematic review and meta-analysis.

AIMS: This study aims to assess differences in severity of short-term (<1 year) and long-term (≥1 year) adverse CV outcomes after PCI in insulin-treated vs. non-insulin-treated diabetes mellitus (DM) patients. METHODS: A systematic search on Pubmed and Embase led to the incorporation of 29 studies that compared post-percutaneous coronary interventional outcomes in insulin-treated and non-insulin-treated diabetes mellitus. Diabetes mellitus (type 2) was defined as fasting blood glucose (FBG) level of >7.0 mmol/L or with an oral glucose tolerance test (OGTT) level of >11.1 mmol/L at least on two separate occasions. Adverse CV outcomes were assessed in insulin-treated and non-insulin-treated DM after the PCI procedure considered for the analyses were mortality, MACE, TLR, TVR, MI, stent thrombosis, target lesion failure (TLF), and need for-post PCI CABG. Data were pooled and analyzed using Review Manager 5.3, and risk ratios (RR) with respective 95% confidence intervals (CI) were calculated.The statistical analyses were carried out by Review Manager v.5.3, and the data were pooled using a random-effects model. Risk ratios (RRs) with 95% confidence intervals (CI) were reported along with forest plots. The chi-square test was performed to assess for differences between the subgroups. Heterogeneity across studies was evaluated using Higgins I2 statistics. Visual inspection of the funnel plot and Begg's regression test were used to assess publication bias. RESULTS: A total of 40,527 patients (11742 in the Insulin-treated diabetes mellitus group and 28785 in the non-insulin-treated DM group) who underwent PCI were included. The pooled analysis of short-term follow up outcomes preceding PCI demonstrated a significantly higher risk of mortality (RR = 1.75 [1.24,2.47]; p = 0.002), MI (RR = 1.81[1.14,2.87]; p = 0.01], stent thrombosis (RR = 1.63[1.13, 2.35]; p = 0.009) and target lesion revascularization (TLR) (RR = 1.29[1.02,1.63]; p = 0.03) in insulin-treated DM patients. Similarly, analysis of long-term follow-up studies depicted a significantly higher risk mortality (RR = 1.55 [1.22, 1.97]; p = 0.0003), MI (RR = 1.63 [1.35, 1.97]; p=<0.00001), MACE (R = 1.47 [1.31, 1.65]; p=<0.00001), stent thrombosis (RR = 1.54 [1.19,1.99]; p = 0.001), TLR (RR = 1.40 [1.18, 1.66]; p = 0.0001), target vessel revascularization (TVR) (RR = 1.35 [1.11, 1.64]; p = 0.003) in insulin-treated DM group after PCI versus non-insulin-treated DM patients. CONCLUSION: Despite a tremendous technical success rate of multi-vessel stenting, people living with diabetes who were being treated with insulin had higher long-term, and short-term mortality rates, MI, TLR, TVR, and stroke compared to people living with diabetes who were being treated with means other than insulin and are more prone to detrimental cardiovascular outcomes.

Use of Tocilizumab in COVID-19: A Systematic Review and Meta-Analysis of Current Evidence.

Background and objectives A flare-up in coronavirus disease 2019 (COVID-19) cases threatens the health of people, and though there is no proven pharmacological treatment, many analytical studies have suggested that interleukin-6 (IL-6) levels are elevated in cases of severe COVID-19 and that the anti-IL-6 biologic agent tocilizumab may be beneficial. This is a critical review of studies aiming to assess the safety and efficacy of tocilizumab as compared to the standard regimen in patients with COVID-19. Materials and methods Online databases (PubMed and Cochrane) were searched until June 29, 2020, for original articles investigating the immunological response in COVID-19 and its treatment with tocilizumab. Data on multiple baseline characteristics and pre-specified endpoints were extracted and pooled using a random effect model. We used Review Manager version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, 2014, Denmark) and Stata 11.0 (Stata Corporation LP, College Station, TX) for all analyses. Risk ratios (RR) and the weighted mean difference (WMD) with the corresponding 95% confidence interval (CI) were calculated. Results From a total of 1,246 identified articles, 13 studies were included after duplicate removal and narrowing based on title and abstract. Of the 13 included studies, seven case-control studies were shortlisted for meta-analysis (quantitative) and six-single arm studies were used in the discussion (qualitative). These studies had 766 patients (351 in the tocilizumab arm and 414 in the control arm). Their pooled analysis demonstrated that mortality was significantly lower in the tocilizumab group (RR=0.56 [0.34, 0.92]; p=0.02; I2=76%), as was the need for artificial invasive ventilation (RR=0.34 [0.12, 0.99]; p=0.05; I2=0%) as compared to the control group. No significant differences were observed between tocilizumab and control group in intensive care unit admissions (RR=0.73 [0.15, 3.59]; p=0.70; I2=60%) and risks of post-drug infection (RR=1.29 [0.41, 4.04]; p=0.66; I2=88%). In terms of efficacy outcome, improved oxygen saturation (RR=1.13 [1.04, 1.65]; p=0.02; I2=0%) was reported to be markedly significant in tocilizumab patients when compared with the standard care group. Conclusions Our results based on pooled studies show tocilizumab to be safe and efficacious in reducing mortality among critically ill COVID-19 patients. However, due to the limited number of observational studies, the positive findings should be viewed cautiously and warrant further investigation.

Exploring Flavonoids for Potential Inhibitors of a Cancer Signaling Protein PI3Kγ Kinase Using Computational Methods.

BACKGROUND/AIM: Phosphatidyl-inositol-3-kinase (PI3K), a cancer therapeutic target, has been exploited for cancer therapy. The natural compounds flavonoids have increasingly been shown to possess anticancer activity. The current study aimed to explore all known flavonoids for their ability to inhibit PI3Kγ. MATERIALS AND METHODS: Virtual screening of flavonoids using molecular docking to the ATP binding site of PI3Kγ was performed. The top 10 scoring flavonoids were selected for pose analysis and binding strength scores. RESULTS: Molecular docking revealed that the 10 selected flavonoids might inhibit PI3Kγ kinase activity. Literature search did not identify studies reporting a bioassay activity for any of these compounds. CONCLUSION: All 10 selected flavonoids are potential PI3Kγ kinase inhibitors and anticancer agents. Interestingly, one of the 10 least scoring flavonoids has been reported to be inactive, as expected, and thus validating the accuracy of the results.

Investigating architecture and structure-function relationships in cold shock DNA-binding domain family using structural genomics-based approach.

Oligonucleotide/oligosaccharide-binding fold (OB-fold) plays a major role in the regulation of central dogma of life via binding though DNA and RNA. The OB-fold domains are diverse in nature and present in large number of proteins with verities of molecular functions. Here, we have investigated the distribution of sequence, structure and repeats of cold shock DNA-binding proteins (CSDB), a member of OB-fold, in all three kingdoms to establish functional relationships. The CSDB is consists of 30 domains with a major contribution of S1 (>110,601 sequences), S12 (>23,760 sequences), S17 (>14,833 sequences) and S28e (>1615 sequence) domains. These domains are largely found in bacteria (70-90%). The number of S1 domain repeats in eukaryota varies from 1 to 15 and are well-correlated with the protein size. The molecular function analysis suggests that a large number of repeats in the S1 domain are involved in diverse molecular functions in bacteria and eukaryotes. In-depth structure analysis of S1, S12, S17 and S28e domain-containing proteins of the OB-fold family provides a reasonable basis to understand the relationship of size and number of repeats with the corresponding molecular functions.

A Short and Efficient Total Synthesis of Ficuseptamines A and B.

A rapid and efficient total synthesis of ficuseptamines A and B by a cross metathesis strategy is described.

In Silico Identification of Novel Erlotinib Analogues Against Epidermal Growth Factor Receptor.

Cancer is one of the major health challenges in modern times. Considering its high mortality rate, many proteins that are linked to cancer have been targeted for therapy, with one of them being the epidermal growth factor receptor (EGFR). A drug that is currently in the market for the treatment of non-small cell lung cancer and targets EGFR is erlotinib. In a quest for improved efficacy of erlotinib, herein we report molecular docking studies of thirteen erlotinib analogues by modification of the alkyne and anilino groups, all of which displayed better binding affinity than erlotinib. We identified aziridinyl analogue (S)- 13B: with the best binding energy of all the analogues studied.

A Short History of the Use of Plants as Medicines from Ancient Times.

A concise historical overview on the use of plants for medical treatments from ancient times is discussed.

Echinococcal Cyst of the Pancreas with Cystopancreatic Duct Fistula Successfully Treated by Partial Cystectomy and Cystogastrostomy.

The primary pancreatic hydatid (echinococcal) cyst is extremely rare with a reported incidence of <1%. Owing to its rareness and a considerable overlap of imaging features, a preoperative diagnosis is usually difficult. The dilemma in confirming this benign diagnosis has often questioned the extent of radical pancreatic resection. The involvement of pancreatic duct (cystopancreatic duct fistula) further complicates the management of such cystic lesions. In this report, we present a case of isolated hydatid cyst of the pancreatic body and tail communicating with the pancreatic duct. Cystogastrostomy preceded by partial cystectomy in the same setting has never been reported to date. The patient had an uneventful postoperative course and follow-up showed no evidence of cyst recurrence or dissemination. We consider this a safe surgical option in longstanding large cysts, especially if a cystopancreatic fistula is detected beforehand. The success of such a procedure however may rely on the size and thickness of the cyst wall to support this anastomosis.

Epigallocatechin-3-gallate inhibits tax-dependent activation of nuclear factor kappa B and of matrix metalloproteinase 9 in human T-cell lymphotropic virus-1 positive leukemia cells.

Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol molecule from green tea and is known to exhibit antioxidative as well as tumor suppressing activity. In order to examine EGCG tumor invasion and suppressing activity against adult T-cell leukemia (ATL), two HTLV-1 positive leukemia cells (HuT-102 and C91- PL) were treated with non-cytotoxic concentrations of EGCG for 2 and 4 days. Proliferation was significantly inhibited by 100 µM at 4 days, with low cell lysis or cytotoxicity. HTLV-1 oncoprotein (Tax) expression in HuT- 102 and C91-PL cells was inhibited by 25 µM and 125 µM respectively. The same concentrations of EGCG inhibited NF-kB nuclearization and stimulation of matrix metalloproteinase-9 (MMP-9) expression in both cell lines. These results indicate that EGCG can inhibit proliferation and reduce the invasive potential of HTLV-1- positive leukemia cells. It apparently exerted its effects by suppressing Tax expression, manifested by inhibiting the activation of NF-kB pathway and induction of MMP-9 transcription in HTLV-1 positive cells.

Mixed SAMs and MALDI-ToF MS: preparation of N-glycosylamine derivative and thioctic acid methyl ester bearing 1,2-dithiolane groups and detection of enzymatic reaction on Au.

Herein, we report an enzymatic galactosylation reaction of ß-glucopyranosylamide 4 and thioctic acid methyl ester 5 bearing 1,2-dithiolane groups to form a new system of mixed self-assembled monolayers (SAMs) on gold. Characterization of the enzymatic activity was conveniently achieved by mass spectrometry.

Recent applications of ring-closing metathesis in the synthesis of lactams and macrolactams.

Lactams are an important class of compounds owing to their presence in numerous biologically active molecules of natural and unnatural nature. They are also highly versatile intermediates that can be elaborated into interesting compounds for potential use in organic and medicinal chemistry endeavors. In this feature article, the reader will be given a background to olefin metathesis followed by concise discussions (with selected examples) to report recent applications of ring-closing metathesis to form lactams and macrolactams from acyclic diene precursors, an area which continues to deposit attractive applications in the chemical literature en route or in the final step to the target molecules.

A convenient approach to acyclic unsaturated amino acids via ring-closing metathesis.

An efficient synthetic methodology to gain access to novel cis- and trans-unsaturated amino acids via ring-closing metathesis in high yields is described.