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Photo-activated microtubule targeting drugs: Advancing therapies for colorectal cancer

World Journal of Gastroenterology 2024年第26期30卷 3257-3260页

作者： naresh singh Samantha Sharma Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202United States

Over the years immunotherapy has demonstrably improved the field of cancer ***,achieving long-term survival for colorectal cancer(CRC)patients remains a significant unmet *** immunotherapies incor-porating targeted drugs like MEK or multi-kinase inhibitors have offered some palliative ***,substantial gaps remain in the current therapeutic armamentarium for *** recent years,there has been a surge of interest in exploring novel treatment strategies,including the application of light-activated drugs in conjunction with optical *** approach holds promise for achie-ving localized and targeted delivery of cytotoxic agents,such as microtubule-targeting drugs,directly to cancerous cells within the colon.

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Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer:Unravelling challenges and future directions

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World Journal of Gastroenterology 2024年第13期30卷 1815-1835页

作者： Samantha Sharma naresh singh Anita Ahmed Turk Isabella Wan Akshay Guttikonda Julia Lily Dong Xinna Zhang Mateusz Opyrchal Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202United States Division of Hematology/Oncology Department of MedicineIndiana University School of MedicineIndianapolisIN 46202United States Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202United States

Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical *** considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely *** the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint *** aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor *** therapies thus have shown promising results in many clinical trials alone or in *** efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical *** trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair ***,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC *** this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the *** review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in *** underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

关键词： Colorectal cancer Immune checkpoint inhibitors Clinical trials Immunotherapy Microsatellite instability Microsatellite stability DNA mismatch repair

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Acoustical properties of a 3D printed honeycomb structure filled with nanofillers:Experimental analysis and optimization for emerging applications

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Defence Technology（防务技术） 2024年第5期35卷 248-258页

作者： Jeyanthi Subramanian Vinoth kumar Selvaraj Rohan singh Ilangovan S naresh Kakur Ruban Whenish School of Mechanical Engineering Vellore Institute of TechnologyChennai600127Tamil NaduIndia Department of Mechanical Engineering SRM Institute of Science and TechnologyRamapuramChennai600089India Department of Chemical Engineering and Materials Science University of Southern CaliforniaLos Angeles90089USA Advanced Materials Research Centre Technology Innovation InstituteAbu Dhabi9639UAE Center for Biomaterials Cellular and Molecular TheranosticsVellore Institute of TechnologyVellore632014Tamil NaduIndia

The novelty of this research lies in the successful fabrication of a 3D-printed honeycomb structure filled with nanofillers for acoustic properties,utilizing an impedance tube setup in accordance with ASTM standard E *** Creality Ender-3,a 3D printer,was used for printing the honeycomb structures,and polylactic acid(PLA)material was employed for their *** organic,inorganic,and polymeric compounds within the composites were identified using fourier transformation infrared(FTIR)*** structure and homogeneity of the samples were examined using a field emission scanning electron microscope(FESEM).To determine the sound absorption coefficient of the 3D printed honeycomb structure,numerous samples were systematically developed using central composite design(CCD)and analysed using response surface methodology(RSM).The RSM mathematical model was established to predict the optimum values of each factor and noise reduction coefficient(NRC).The optimum values for an NRC of 0.377 were found to be 1.116 wt% carbon black,1.025 wt% aluminium powder,and 3.151 mm distance between parallel ***,the results demonstrate that a 3Dprinted honeycomb structure filled with nanofillers is an excellent material that can be utilized in various fields,including defence and aviation,where lightweight and acoustic properties are of great importance.

关键词： 3D printing Honeycomb structure Acoustics Field emission scanning electron microscope Response surface methodology

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IgE regulates airway smooth muscle phenotype:Future perspectives in allergic asthma

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World Journal of Immunology 2016年第3期6卷 126-130页

作者： naresh singh Redhu Abdelilah S Gounni Division of GI/Nutrition Boston Children's Hospital Harvard Medical School Department of Immunology Faculty of Health Sciences College of Medicine University of Manitoba

The purpose of this commentary is to highlight the emerging role of IgE on airway smooth muscle(ASM) cells function through activation of the high-affinity Fc receptor for IgE. We discuss the potential implications of... 详细信息

关键词： IgE Airway Allergic asthma Remodeling Inflammation

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Acoustical properties of a 3D printed honeycomb structure fi lled with nanofi llers: Experimental analysis and optimization for emerging applications

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Defence technology 2024年第5期 248页

作者： Jeyanthi Subramanian Vinoth kumar Selvaraj Rohan singh Ilangovan S naresh Kakur Ruban Whenish

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Thyroid dysfunction and developmental anomalies in first degree relatives of children with thyroid dysgenesis

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世界儿科杂志:英文版 2016年第2期12卷 215-218页

作者： Lakshminarasimhan Sindhuja Devi Dayal Kushaljit singh Sodhi naresh Sachdeva Anish Bhattacharya Pediatric Endocrinology Unit Department of PediatricsPostgraduate Institute of Medical Education and ResearchChandigarh Department of Radiodiagnosis Postgraduate Institute of Medical Education and ResearchChandigarh Department of Endocrinology Postgraduate Institute of Medical Education and ResearchChandigarh Department of Nuclear Medicine Postgraduate Institute of Medical Education and ResearchChandigarh

Background: Familial clustering in patients withpermanent congenital hypothyroidism (CH) caused bythyroid dysgenesis (TD) has been reported in developedcountries. There is no information on familial TD fromdeveloping ***: A total of 312 first degree relativesbelonging to 80 families of children with TD (group 1)and 40 families of age-matched normal children (group2) were screened by thyroid ultrasonography, serum totalthyroxine (T4) and thyroid stimulating hormone (TSH).Results: Thyroid scintigraphy revealed agenesis in78.7% of the patients, ectopic gland in 15%, and hypoplasiain 6.2%. The mean thyroid volumes were similar in parentsand siblings of both groups. Eight (10.6%) mothers in group1 were identified to have thyroid hypoplasia as comparedwith none in group 2 (P=0.03). Serum TSH was signifi cantlyhigher in group 1 than in group 2 (P=0.004). Sixteen (7.8%)subjects (6 mothers, 5 fathers, and 5 siblings) in group 1were found to have subclinical hypothyroidism as comparedto none in group 2 (P<0.05). Four families were identifiedto have thyroid developmental anomalies and abnormalthyroid functions accounting for 5% of cases of familial TDin our ***: Thyroid developmental anomalies andthyroid function abnormalities are more frequent in firstdegree relatives of children with TD as compared with acontrol population. These findings suggest that possiblythere is a genetic component of TD in Indian patients.

关键词： congenital hypothyroidism familial occurrence first degree relatives thyroid developmental anomalies thyroid dysgenesis

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Estimation of Sex by Applying Discriminant Function Analysis on Osteo-metric Parameters of Clavicle in Population of Haryana

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Journal of Forensic Science and Medicine 2023年第2期9卷 106-111页

作者： Arun Kumar Luv Sharma Archana Gaurav Kaushik naresh Saini Ravi Kanth Soni Mohan singh Meena Department of Forensic Medicine National Institute of Medical Sciences and ResearchNIMS UniversityJaipurRajasthanIndia Department of Forensic Medicine PGIMSRohtakHaryanaIndia Department of Organaon of Medicine Sri Ganganagar Homeopathic Medical CollegeSri GanganagarRajasthanIndia

It is important to pinpoint the identity of the deceased in scenarios such as decomposed bodies,skeletonized remains,mutilated remains,exhumed dead bodies,and in mass *** are many important parameters to establish the identity of a *** estimation of sex is one of *** of sex from bones is easy when the whole skeleton is available,but it becomes difficult when the body is mutilated and only parts of the body or bones are *** present study is undertaken to estimate the sex by applying discriminant function analysis(DFA)on various osteo-metric parameters of the clavicle in the population of *** hundred pairs of clavicles were collected from the bodies brought for *** were macerated and air dried for the removal of soft *** variables of clavicle of both sexes were measured and analyzed using the analysis of variance test which provided descriptive *** of the values helped in sexing of the *** of sex from different parameters of the clavicle was possible with overall accuracy of 93%in original and 92.5%in crossvalidated cases among total *** was 96%and 90%in original and 96%and 89%in cross validated cases among males and females respectively,indicating a strong correlation in estimation of sex of a person from the *** most important parameters to determine the sex from the clavicle are length of clavicle,mid clavicular circumference of clavicle,weight of clavicle,transverse diameter of lateral end of right clavicle,and longitudinal diameter of medial end of the left clavicle.

关键词： Clavicle estimation of sex identification

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A Combination of Antigen Retrieval Methods Significantly Enhances the Unmasking of Tedious Antigens of Lymphangiogenesis and Angiogenesis in Canine Mammary Tumour

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Journal of Biosciences and Medicines 2017年第12期5卷 44-55页

作者： Parmeet Pal singh naresh Kumar Sood Department of Veterinary Pathology College of Veterinary Science Guru Angad Dev Veterinary and Animal Sciences University Ludhiana India

The use of immunohistochemical techniques has enhanced the diagnostic intensities in pathology. The sensitivity and specificity of any immunohistochemical protocol mainly depends on the ability to unmask antigen from formalin fixed tissue. Various combinations of antigen retrieval protocols have been used to unmask antigen efficiently but none has been established as a flawless one. These protocols either have one or the other lacunae, lacking repeatability under same conditions. In our study, we tried to develop a standardized immunohistochemical protocol for the identification of blood and lymphatic vessels in tissue sections of canine mammary tumour (CMT) using recently identified markers. The combined effects of antigen retrieval (AR) methods including pH shock by Heat-induced epitope retrieval (HIER) and Protease-induced epitope retrieval (PIER) were found highly effective in retrieval of tedious antigens of lymphangiogenesis and angiogenesis. The use of combined antigen retrieval technique for the unmasking of antigens from over fixed, old formalin fixed paraffin embedded (FFPE) canine mammary tumour sections resulted in efficient unmasking of epitopes when compared with the individual antigen retrieval methods.

关键词： Angiogenesis Antigen Retrieval Canine Mammary Tumour Immunohistochemistry Lymphangiogenesis

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Physio-pathology of induced endotoxaemia in bovine and its treatment regimen

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Journal of Biomedical Science and Engineering 2013年第11期6卷 1077-1084页

作者： Irtiza Nabi Digvijay singh naresh Kumar Sood Department of Veterinary Pathology College of Veterinary Science Guru Angad Dev Veterinary and Animal Sciences University Ludhiana India Department of Veterinary Physiology and Biochemistry College of Veterinary Science Guru Angad Dev Veterinary and Animal Sciences University Ludhiana India

Endotoxic shock was induced in five apparently healthy male buffalo calves by i.v infusion of Escherichia coli endotoxin at 5microgram/kilogram (μg/Kg) body weight/hour (BW/hr) for 3 hours. Endotoxin infusion caused clinical signs of restlessness, respiratory distress, snoring, diarrhoea, profuse salivation along with the significant hypoproteinemia, hypoalbuminemia and hypokalemia in all the animals. The animals were observed up to day 4 or death, whichever was earlier. The treatment with one time intravenous infusion of hypertonic saline solution @ 4milliliter/Kilogram body weight (ml/Kg?BW), dextran-40 @ 10 ml/Kg?BW, flunixin meglumine @ 1.1 milligram/Kg?BW (mg/Kg?BW) and blood @ 20 ml/Kg?BW to these animals alleviated the clinical signs and significantly raised the circulating glucose level at 4.5 and 5.5 hrs. The treatment led to survival of three of the five endotoxemic buffalo calves. The significant hypoproteinemia, hypoalbuminemia, hypokalemia and hypoglobulinemia continued even after treatment. Gross and histopathologic findings of congestion, haemorrhage, necrosis in vital organs viz., lungs, liver, kidneys, brain and intestines were suggestive of endotoxin induced hypoxia and multi-organ failure. Additionally, emphysema and fibrinous thrombi in microvasculature of lungs were salient histopathological findings indicating terminal respiratory failure in the remaining two dead endotoxemic buffalo calves. From clinical signs, plasma chemistry and pathological lesions, it was concluded that endotoxemia led to a disruption of critical life processes, but a timely and effective treatment could counter these deleterious effects and save precious lives.

关键词： Blood Buffalo Calves Dextran-40 Endotoxemia Flunixin Meglumine Hypertonic Saline Physiology Pathology

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Comparison of phenotypic markers and neural differentiation potential of multipotent adult progenitor cells and mesenchymal stem cells

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World Journal of Stem Cells 2013年第2期5卷 53-60页

作者： Saurabh Pratap singh naresh Kumar Tripathy Soniya Nityanand Stem Cell Research Facility Department of Hematology Sanjay Gandhi Post-Graduate Institute of Medical SciencesLucknow 226014 India

AIM: To compare the phenotypic and neural differentiation potential of human bone marrow derived multipotent adult progenitor cells (MAPC) and mesenchymal stem cells (MSC). METHODS: Cultures of MAPC and MSC were established in parallel from same samples of human bone marrow (n = 5). Both stem cell types were evaluated for expression of pluripotency markers including Oct-4 and Nanog by immunocytochemistry and reversetranscription polymerase chain reaction (RT-PCR) and expression of standard mesenchymal markers including CD14, CD34, CD44, CD45, CD73, CD90, CD105 andhuman leukocyte antigen (HLA)-ABC by flow cytometry. After treatment with neural induction medium both MAPC and MSC were evaluated for expression of neural proteins [neuronal filament-200 (NF-200) and glial fibrillar acidic protein (GFAP)] by immunocytochemistry and Western blotting and neural genes [NF-200, GFAP, Tau, microtubule-associated protein (MAP)-1B, MAP-2, neuron-specific enolase (NSE) and oligodendrocyte-1 (Olig-1)] by quantitative real-time-PCR. RESULTS: MAPC had small trigonal shaped while MSC had elongated spindle-shaped morphology. The MAPC expressed Oct-4 and Nanog both at gene and protein levels, whereas MSC were negative for these pluripotent markers. MAPC were negative for HLA-ABC while MSC had high expression of HLA-ABC. In addition, MAPC as compared to MSC had significantly lower expression of CD44 (36.56% ± 1.92% vs 98.23% ± 0.51%), CD73 (15.11% ± 2.24% vs 98.53% ± 2.22%) and CD105 (13.81% ± 3.82%vs 95.12% ± 5.65%) (P < 0.001, for all) MAPC cultures compared to MSC cultures treated with neural induction medium had significantly higher fold change expression of NF-200 (0.64), GFAP (0.52), Tau (0.59), MAP-2 (0.72), Olig-1 (0.18) and NSE (0.29) proteins (P < 0.01 for Olig-1 and P < 0.001 for rest) as well as higher fold change expression of genes of NF-200 (1.34),GFAP (1.12),Tau (1.08),MAP-1B (0.92), MAP-2 (1.14) andNSE (0.4) (P < 0.001 for all). CONCLUSION: MAPC can be differentially cha

关键词： Bone marrow Human multipotent adult progenitor cells Human mesenchymal Stem cells Phenotypic markers Neural differentiation

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