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26 result(s) for "Parasher, Gulshan"
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Novel role of folate (vitamin B9) released by fermenting bacteria under Human Intestine like environment
The anaerobic region of the gastrointestinal (GI) tract has been replicated in the anaerobic chamber of a microbial fuel cell (MFC). Electroactive biomolecules released by the facultative anaerobes ( Providencia rettgeri ) under anoxic conditions have been studied for their potential role for redox balance. MALDI study reveals the presence of vitamin B9 (folate), 6-methylpterin, para-aminobenzoic acid (PABA) and pteroic acid called pterin pool. ATR-FTIR studies further confirm the presence of the aromatic ring and side chains of folate, 6-methylpterin and PABA groups. The photoluminescence spectra of the pool exhibit the maximum emission at 420, 425, 440, and 445 nm when excited by 310, 325, 350, and 365 nm wavelengths (day 20 sample) highlighting the presence of tunable bands. The cyclic voltammetric studies indicate the active participation of pterin pool molecules in the transfer of electrons with redox potentials at − 0.2 V and − 0.4 V for p-aminobenzoate and pterin groups, respectively. In addition, it is observed that under prolonged conditions of continuous oxidative stress (> 20 days), quinonoid tetrahydrofolate is formed, leading to temporary storage of charge. The results of the present study may potentially be useful in designing effective therapeutic strategies for the management of various GI diseases by promoting or blocking folate receptors.
Lipid membrane-camouflaged biomimetic nanoparticle for MicroRNA based therapeutic delivery to intestinal epithelial cells
We have made artificial extracellular vesicles like nanoparticles that contain biologically active Agomir (miRNA mimic)/Antagomir (miRNA inhibitor) adsorbed on magnetic ZnO particles bound by a lipid bilayer membrane from Caco-2 cells (human colorectal adenocarcinoma), which we examined for use as therapeutic nanoparticles or as delivery vehicles for therapeutic agents to the gut epithelia. Magnetic ZnO nanoparticles were synthesized using Manganese doping in both solid-state reaction (SSR) and alkaline aqueous solution methods. The SSR method exhibited ferromagnetic behavior, whereas the alkaline solution method yielded a nanorod-like morphology. Encapsulation was demonstrated using mercaptosuccinic acid. These biocompatible nanoparticles, owing to their nanorod-like morphology with larger surface area, were used to adsorb miR200c antagomir/agomir molecules as well as assemble lipid membrane fragments from Caco-2 cells. We performed various in vivo efficacy studies of Caco-2 NanoVesicles (CNVs) (Caco-2NanoVesicles) or detrimental CNV (therapeutic Caco-2 NanoVesicles (tCNVs)) loaded with miR200c Agomir that degrade occludin protein-coding mRNA as a proof of concept for clinical use of the Antagomir counterpart. There was no discernible toxicity, mortality, or systemic inflammatory or immunological responses in mice following administration of either CNVs or tCNVs. tCNV administration enhances intestinal permeability in mice. This supports their use as biological Nano-therapeutics to restore the gut barrier.
MicroRNA in Pancreatic Cancer: From Biology to Therapeutic Potential
Pancreatic cancer is one of the most aggressive malignancies, accounting for more than 45,750 deaths annually in the U.S. alone. The aggressive nature and late diagnosis of pancreatic cancer, coupled with the limitations of existing chemotherapy, present the pressing need for the development of novel therapeutic strategies. Recent reports have demonstrated a critical role of microRNAs (miRNAs) in the initiation, progression, and metastasis of cancer. Furthermore, aberrant expressions of miRNAs have often been associated with the cause and consequence of pancreatic cancer, emphasizing the possible use of miRNAs in the effective management of pancreatic cancer patients. In this review, we provide a brief overview of miRNA biogenesis and its role in fundamental cellular process and miRNA studies in pancreatic cancer patients and animal models. Subsequent sections narrate the role of miRNA in, (i) cell cycle and proliferation; (ii) apoptosis; (iii) invasions and metastasis; and (iv) various cellular signaling pathways. We also describe the role of miRNA’s in pancreatic cancer; (i) diagnosis; (ii) prognosis and (iii) therapeutic intervention. Conclusion section describes the gist of review with future directions.
1878 Migration of Over-the-Scope Clip (OTSC) Resulting in Intestinal Obstruction
INTRODUCTION:Iatrogenic perforations are a known and feared complication of diagnostic and therapeutic colonoscopy. Over-the-scope clips (OTSCs) have recently been utilized for management of these perforations. We present the case of a 40-year-old male patient treated with over-the-scope (Ovesco®) clip for an iatrogenic post-polypectomy perforation with subsequent intestinal obstruction occurring as a result of migration of the clip.CASE DESCRIPTION/METHODS:A 40-year-old male with familial adenomatous polyposis and total proctocolectomy, ileoanal anastomosis and a J pouch had an ileoscopy performed for polyp surveillance. A 3 cm flat polyp was removed with Eleview® injection lift technique. A hole like defect was noted in the postpolypectomy site that developed into an obvious small 2-3 mm perforation. To repair the defect, a one 14/6 mm type gc over-the-scope clip (Ovesco®) and a 12/6 mm type gc over-the-scope clip (Ovesco®) was successfully placed. Four months later the patient presented to the emergency department with severe anal pain. He felt a hard metallic object in the anal canal. He denied any fevers, chills, nausea, vomiting, or abdominal pain. Rectal tenderness was found on digital rectal examination. A CT abdomen and pelvis showed an object of metallic density at the anal verge with nonobstructive bowel gas pattern. Colonoscopy revealed two over-the-scope clips approximately 2 cm from the anal verge embedded in the mucosa (Figure 1) which were removed. The patient did well post procedure and was discharged home the next day.DISCUSSION:The Ovesco® clip (Ovesco, Tübingen, Germany) is a novel endoscopic method to achieve mechanical compression of gastrointestinal tissue with current indications including closure of fistulas, iatrogenic perforations, hemostasis and non-variceal gastrointestinal bleeding. Iatrogenic perforations during colonoscopy have an incidence ranging from 0.1% to 0.3% of cases. These complications carry a high mortality rate and in the past warranted surgical intervention. However, with the advances in therapeutic endoscopy many perforations can be managed effectively with endoclips, OTSCs and/or endosuturing. These new techniques do come with device-specific risks. Fischer et al. reported the first case of OTSC-induced bowel obstruction. Here we present another case of bowel obstruction as a result of OTSC placement for a perforation, treated with surgical intervention. All gastroenterologists should be aware of clinical scenarios in which the Ovesco clip can be used.
Colorectal Cancer Survival Trends in the United States From 1992 to 2018 Differ Among Persons From Five Racial and Ethnic Groups According to Stage at Diagnosis: A SEER-Based Study
Introduction Survival following colorectal cancer (CRC) has improved in the US since 1975, but there is limited information on stage-specific survival trends among racial and ethnic subgroups. Objectives The purpose of this study was to estimate and compare trends in 1- and 5-year CRC cause-specific survival in the United States by both stage and race/ethnicity. Methods We performed a retrospective cohort study of individuals diagnosed with CRC using the 1992-2018 Surveillance, Epidemiology and End Results (SEER) database. We estimated and compared time trends in 1- and 5-year survival for CRC stage by race/ethnicity. Results Data from 399 220 individuals diagnosed with CRC were available. There were significant differences in stage-specific 1-year survival trends by race and ethnicity. Differences were most notable for distant stage CRC: survival probabilities increased most consistently for non-Hispanic American Indian/Alaska Native (AIAN) and Black (NHB) persons, but their trend lines were lower than those of Hispanic, and non-Hispanic Asian/Pacific Islander (API) and White (NHW) persons, whose initially greater gains appear to be slowing. Although the data do not support significant racial/ethnic differences in 5-year CRC survival trends by stage, AIAN and NHB persons have the lowest average survival probabilities for multiple CRC stages, and no racial/ethnic group has 5-year survival probabilities above 20% for distant-stage CRC. Conclusion Although there has been an overall improvement in adjusted CRC-specific survival probabilities since 1992, AIAN and NHB persons continue to experience worse prognosis than those of other races/ethnicities. This highlights the importance of reinvigorating efforts to understand the causes of mortality in CRC, including those which may differ according to an individual’s race or ethnicity.