Publications by authors named "Aditi Sharma"

146 Publications

Pinus roxburghii alleviates bone porosity and loss in postmenopausal osteoporosis by regulating estrogen, calcium homeostasis and receptor activator of nuclear factor-κB, osteoprotegerin, cathepsin bone markers.

J Pharm Pharmacol 2021 Mar 26. Epub 2021 Mar 26.

School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, India.

Objectives: The study was aimed to evaluate the potential of hydroalcoholic extract of Pinus roxburghii (PRE) stem bark in post-menopausal osteoporosis and its underlying mechanisms.

Methods: In silico docking of the markers was done using AutoDock version 4.2. for molecular targets: receptor activator of nuclear factor-κB (RANK), osteoprotegerin (OPG) and Cathepsin. Female Wistar rats of bodyweight 200-250 g were employed and surgical ovariectomy (OVX) was performed. PRE was administered at a dose of 100 and 200 mg/kg whereas standard drug, raloxifene given at 1 mg/kg orally for eight weeks.

Key Findings: PRE (20 and 40 µg/mL) significantly increased the cellular proliferation in osteoblastic UMR cell lines 11.58 and 15.09% respectively. Eight weeks after surgical removal of ovaries, a significant bone porosity was confirmed by modulation in bone breaking strength of tibia, lumber, and femur; bone mineral density (BMD), calcium, phosphorus, hydroxyproline levels in OVX group. Treatment with PRE 100 and 200 mg/kg significantly restored the bone loss. Real-time polymerase chain reaction (RT-PCR) analysis of molecular markers RANK, OPG and cathepsin and histology also confirmed the attenuation of bone loss. The quantification of quercetin, gallic acid, caffeic acid, catechin, tannic acid and ascorbic acid was done by high-performance liquid chromatography (HPLC) and high performance thin layer chromatography.

Conclusions: P. roxburghii produced anti-osteoporotic effect possibly due to estrogenic modulation, and improved bone remodeling.
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http://dx.doi.org/10.1093/jpp/rgaa014DOI Listing
March 2021

Emotional and Behavioral Dysregulation in Severe Mental Illness.

Child Adolesc Psychiatr Clin N Am 2021 Apr 15;30(2):415-429. Epub 2021 Feb 15.

Department of Psychiatry and Behavioral Sciences, University of Washington, 8805 Steilacoom Boulevard Southwest, Lakewood, WA 98498, USA. Electronic address:

Emotional and behavioral dysregulation are common in severe mental illnesses, including schizophrenia, bipolar disorder, and borderline personality disorder. Emotional instability and behavioral outbursts can be driven by internal processes and/or environmental triggers and interpersonal interactions. Understanding the underlying diagnosis is important in determining the best course of treatment. Disorder-specific treatments are important in addressing underlying drivers of emotional dysregulation, irritability, and aggression. Coping skills training and behavioral modification strategies have broad applicability and are useful for aggression and irritability. Treatment planning to address emotion dysregulation and aggression in severe mental illness should address psychiatric comorbidities, substance use, and medication adherence.
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http://dx.doi.org/10.1016/j.chc.2020.10.010DOI Listing
April 2021

Validation of Available Extended Spectrum Beta-Lactamase (ESBL) Clinical Scoring Models in Predicting Drug Resistance in Patients with Enteric Gram- Negative Bacteremia, Treated at South Texas Veterans Health Care System (STVHCS).

Antimicrob Agents Chemother 2021 Mar 15. Epub 2021 Mar 15.

South Texas Veterans Health Care System (STVHCS), San Antonio, Texas, USA.

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are increasingly common; however, predicting which patients are likely to be infected with an ESBL pathogen is challenging, leading to increased use of carbapenems. To date, five prediction models have been developed to distinguish between patients infected with ESBL pathogens. The aim of this study was to validate and compare each of these models, to better inform antimicrobial stewardship. This was a retrospective cohort study of patients with gram-negative bacteremia treated at the South Texas Veterans Health Care System over 3 months from 2018 to 2019. We evaluated isolate, clinical syndrome, and score variables for the five published prediction models/scores: Italian "Tumbarello", Duke, University of South Carolina (USC), Hopkins Clinical Decision Tree, and Modified Hopkins. Each model was assessed using the receiver-operating-characteristic curve (AUROC) and Pearson correlation. 145 patients were included for analysis, of which 20 (13.8%) were infected with an ESBL or The most common sources of infection were genitourinary (55.8%) and gastrointestinal/intraabdominal (24.1%) and the most common pathogen was (75.2%). The prediction model with the strongest discriminatory ability (AUROC) was Tumbarello (0.7556). Correlation between prediction model score and percent ESBL was strongest with Modified Hopkins (R2=0.74). In this veteran population, the Modified Hopkins and Duke prediction models were most accurate in discriminating between gram-negative bacteremia patients when considering both AUROC and correlation. However, given the moderate discriminatory ability, many patients with ESBL Enterobacteriaceae (at least 25%) may still be missed empirically.
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http://dx.doi.org/10.1128/AAC.02562-20DOI Listing
March 2021

Modeling Novel Anti-Viral Peptides (AVPs) with in-silico Docking Simulations Against Corona Virus.

Mater Today Proc 2021 Feb 27. Epub 2021 Feb 27.

Department of Computer Sciences, Graphic Era Deemed to be University, Dehradun, Uttarakhand.

The havoc created by Corona virus has been dealt with using various integrative approaches adopted by laboratories through-out the world. Use of anti-viral peptides (AVPs) although new but has shown tremendous potential against many pathogens. Previously AVPs have been designed against spike protein of corona virus which is the major entry mediating molecule. Using various in-silico strategies, in this research work AVPs have been modeled against lesser studied viral proteins namely ORF7a protein, Envelope protein (E), Nucleoprotein (N), and Non-Structural protein (Nsp1 and Nsp2). The predicted AVPs have been docked against various host as well as viral proteins. The interaction of small AVPs seems capable of interfering with binding between viral protein and its host counterpart. Therefore, these AVPs can act as a deterrent against novel corona virus, which requires further validation through laboratory techniques.
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http://dx.doi.org/10.1016/j.matpr.2021.02.377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914030PMC
February 2021

Immunization with Calreticulin Protein Generates Robust Antiparasitic Immunity and Offers Protection during Experimental Lymphatic Filariasis.

ACS Infect Dis 2021 Apr 5;7(4):790-799. Epub 2021 Mar 5.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

Lymphatic filariasis causes permanent and long-term disability worldwide. Lack of potent adulticidal drugs, the emergence of drug resistance, and the nonavailability of effective vaccines are the major drawbacks toward LF elimination. However, immunomodulatory proteins present in the parasite secretome are capable of providing good protection against LF and thus offer hope in designing new vaccines against LF. Here, we evaluated the immunogenicity and protective efficacy of calreticulin protein (BmCRT) using and approaches. Stimulation with recombinant BmCRT (rBmCRT) significantly upregulated Th1 cytokine production in mouse splenocytes, mesenteric lymph nodes (mLNs), and splenic and peritoneal macrophages (PMΦs). Heightened NO release, ROS generation, increased lymphocyte proliferation, and increased antigen uptake were also observed after rBmCRT exposure. Mice immunized with rBmCRT responded with increased Th1 and Th2 cytokine secretion and exhibited highly elevated titers of anti-BmCRT specific IgG at day 14 and day 28 postimmunization while splenocytes and mLNs from immunized mice showed a robust recall response on restimulation with rBmCRT. Infective larvae (L3) challenge and protection studies undertaken in , a permissive model for LF, showed that rBmCRT-immunized animals mounted a robust humoral immune response as evident by elevated levels of total IgG, IgG1, IgG2a, IgG2b, and IgG3 in their serum even 150 days after L3 challenge, which led to significantly reduced microfilariae and worm burden in infected animals. BmCRT is highly immunogenic and generates robust antiparasitic immunity in immunized animals and should therefore be explored further as a putative vaccine candidate against LF.
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http://dx.doi.org/10.1021/acsinfecdis.0c00565DOI Listing
April 2021

Burden and impact of arrhythmias in asthma-related hospitalizations: Insight from the national inpatient sample.

J Arrhythm 2021 Feb 17;37(1):113-120. Epub 2020 Nov 17.

Department of Pulmonary Critical Care and Sleep Division Wayne State University Detroit MI USA.

Background: This study aimed to analyze the burden and impact of cardiac arrhythmias in adult patients hospitalized with asthma exacerbation using the nationwide inpatient database.

Methods: We used the National Inpatient Sample (NIS) database (2010-2014) to identify arrhythmias in asthma-related hospitalization and its impact on inpatient mortality, hospital length of stay (LOS), and hospitalization charges. We also used multivariable analysis to identify predictors of in-hospital arrhythmia and mortality.

Results: We identified 12,988,129 patients hospitalized with primary diagnosis of asthma; among them, 2,014,459(16%) patients had cardiac arrhythmia. The most frequent arrhythmia identified is atrial fibrillation (AFib) (8.95%). The AFib and non-AFib arrhythmia group had higher mortality (3.40% & 2.22% vs 0.74%), mean length of stay (LOS) (5.9 & 5.4 vs 4.2 days), and hospital charges ($53,172 & $51,105 vs $34,585) as compared to the non-arrhythmia group ( < .005). Predictors of arrhythmia in asthma-related hospitalization were history of PCI or CABG, valvular heart disease, congestive heart failure (CHF), and acute respiratory failure. Predictors of higher mortality in arrhythmia group were acute respiratory failure, sepsis, and acute myocardial infarction.

Conclusions: Around 16% of adult patients hospitalized with asthma exacerbation experience arrythmia (mostly AFib 8.95%). The presence of arrhythmias was associated with higher in-hospital mortality, LOS, and hospital charges in hospitalized asthmatics.
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http://dx.doi.org/10.1002/joa3.12452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896478PMC
February 2021

Mitochondrial Dysfunction in Huntington's disease: Pathogenesis and Therapeutic Opportunities.

Curr Drug Targets 2021 Feb 23. Epub 2021 Feb 23.

Department of Pharmacy, Faculty of Pharmacy, University of Oradea. Romania.

Huntington's disease (HD) is prototypical neurodegenerative disease, preferentially disrupts the neurons of striatum and cor-tex. Progressive motor dysfunctions, psychiatric disturbances, behavioural impairments and cognitive decline are the clinical symptoms of HD progression. The disease occurs due to, expanded CAG repeats in exon 1 of huntingtin protein (mHtt) causing its aggregation. Multiple cellular and molecular pathways are involved in the HD pathology. Mitochondria as vital organelles has an important role in most of the neurodegenerative diseases like HD. Over the years, the role of mitochondria in neurons are highly diverged, it not only contribute as cell power source, but as a dynamic organelles it fragments and then fuse to attain a maximal bioenergetics performance, regulate intracellular calcium homeostasis, reactive oxygen species (ROS) generation, antioxidant activity and involved in apoptotic pathways. Indeed, these events are seen to be affected in HD, resulting in neuronal dysfunction in pre-symptomatic stages. mHtt causes critical transcriptional abnormality by altering the expression of a master co-regulator, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), leading to increased susceptibility to oxidative stress and neuronal degeneration. Moreover, mHtt influences multiple cellular signal-ling events which ends with mitochondrial biogenesis. Here, we resume recent findings that pose mitochondria as an im-portant regulatory organelle in HD and how mHtt affects mitochondrial function, trafficking and homeostasis and makes neurons prone to degeneration. In addition, we also uncover the mitochondrial based potential targets and therapeutic ap-proaches with imminent or currently ongoing clinical trials.
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http://dx.doi.org/10.2174/1389450122666210224105945DOI Listing
February 2021

Forty-One-Year-Old Man with Pulmonary Embolism 5 Months After COVID-19.

Clin Med Insights Circ Respir Pulm Med 2021 8;15:1179548420986659. Epub 2021 Feb 8.

Department of Pulmonary Critical Care & Sleep Division, Wayne State University, Detroit, MI, USA.

Background: Hypercoagulation is one of the striking features of COVID-19. Patients hospitalized with COVID-19 are at high risk for venous thromboembolism. However, it is unknown if the risk for venous thromboembolism persists after discharge.

Case Summary: We report a case with pulmonary embolism 5 months after COVID-19. No risk factors for venous thrombosis have been identified.

Conclusion: In COVID-19 related hospitalization, large studies are needed to identify the risk of venous thromboembolism after discharge.
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http://dx.doi.org/10.1177/1179548420986659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876743PMC
February 2021

A qualitative investigation of Orthorexia Nervosa among U.S. college students: Characteristics and sociocultural influences.

Appetite 2021 Feb 20;162:105168. Epub 2021 Feb 20.

APPEAR, Department of Applied Psychology, Northeastern University, Boston, USA; Department of Psychiatric Emergency & Acute Care, Lapeyronie Hospital, CHRU Montpellier, France. Electronic address:

Background: Current studies on Orthorexia Nervosa (ON) are predominantly correlational and have largely been conducted outside of the U.S. with little attention to cultural aspects. This study aimed to qualitatively examine ON-related attitudes and behaviors among U.S. college students, with a particular focus on exploring concerns related to healthy eating and diet quality as defined by proposed diagnostic criteria, body image concerns and disordered eating, and sociocultural influences.

Method: Eighteen women and 3 men, aged 18-23 years (M = 19.5, SD = 1.6), who had reported high levels of ON symptoms participated in individual interviews. Interviews were transcribed verbatim and examined for evidence of the proposed diagnostic criteria of ON. In addition, thematic analysis was conducted to examine concurrent body image and eating concerns, as well as sociocultural influences.

Results: The patterns of the presence of diagnostic criteria varied, with the importance of food quality, and associated severely restricted eating patterns emerging as some of the most common elements. Six themes emerged from the thematic analysis: healthy eating concerns and diet quality, frequency and nature of food-related thoughts, definitions of healthy eating and healthy foods, disordered eating and body image, interpersonal social influence, and media and other influence from the broader social context.

Discussion: The findings suggest that ON symptoms may be concurrent with, or an evolution of other eating disorder presentations. In addition, our results highlight the role of family and sociocultural factors in ON, pointing to the usefulness of examining these behaviors within sociocultural frameworks that have been successfully applied to other types of disordered eating.
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http://dx.doi.org/10.1016/j.appet.2021.105168DOI Listing
February 2021

Reconstruction of an Oblong Nasal Tip Defect.

Dermatol Surg 2021 Feb 8. Epub 2021 Feb 8.

University of California, Irvine, Department of Dermatology; University of California, Irvine, School of Medicine; Private Practice, Newport Skin Cancer, Newport Beach, California.

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http://dx.doi.org/10.1097/DSS.0000000000002890DOI Listing
February 2021

Fatal epidural abscess from diabetic foot disease.

Endocrinol Diabetes Metab Case Rep 2021 Feb 9;2021. Epub 2021 Feb 9.

Department of Endocrinology and Diabetes, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.

Summary: Infection is a common complication of advanced diabetic foot disease, increasing the risk of acute admission and amputation. It is less well-known that foot ulceration and osteomyelitis may cause bacteraemia-associated hematogenous seeding and subsequent epidural abscess formation. Here we describe the case of a 57-year-old woman with known diabetic foot ulcer with underlying osteomyelitis admitted with backpain in the absence of trauma. Her condition deteriorated secondary to overwhelming sepsis. MRI of the spine confirmed spondylodiscitis and posterior epidural collection, not amenable to surgical intervention due to patient's comorbidities and high surgical risk. Despite prolonged antibiotic therapy, the patient died following a hospital admission lasting 2.5 months. This case highlights the importance of regular contact with diabetes foot service for optimisation and prompt treatment of diabetic foot disease, which can be an underestimated potential source of remote site invasive systemic infection. Secondly, high clinical suspicion in admitting clinicians is imperative in ensuring timely diagnosis and early intervention to minimise fatal consequences.

Learning Points: Approximately 10% of patients with diabetes will develop a foot ulcer in their lifetime. Spondylodiscitis (incorporating vertebral osteomyelitis, spondylitis and discitis) is a rare condition and diabetes is the most common predisposing risk factor. Spondylodiscitis often presents with no other symptom other than back pain. Neurological or infective symptoms can be present or absent. High clinical suspicion in clinicians is imperative in ensuring timely diagnosis and early intervention to minimise devastating consequences.
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http://dx.doi.org/10.1530/EDM-20-0129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923128PMC
February 2021

The state of adolescent menstrual health in low- and middle-income countries and suggestions for future action and research.

Reprod Health 2021 Feb 8;18(1):31. Epub 2021 Feb 8.

UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland.

In recognition of the opportunity created by the increasing attention to menstrual health at global, regional, and national levels, the World Health Organization's Department of Sexual and Reproductive Health and Research and the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction convened a global research collaborative meeting on menstrual health in adolescents in August 2018. Experts considered nine domains of menstrual health (awareness and understanding; stigma, norms, and socio-cultural practices; menstrual products; water and sanitation; disposal; empathy and support; clinical care; integration with other programmes; and financing) and answered the following five questions: (1) What is the current situation? (2) What are the factors contributing to this situation? (3) What should the status of this domain of adolescent menstrual health be in 10 years? (4) What actions are needed to achieve these goals? (5) What research is needed to achieve these goals? This commentary summarizes the consensus reached in relation to these questions during the expert consultation. In doing so, it describes the state of adolescent menstrual health in low- and middle-income countries and sets out suggestions for action and research that could contribute to meeting the holistic menstrual health needs of adolescent girls and others who menstruate worldwide.
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http://dx.doi.org/10.1186/s12978-021-01082-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869499PMC
February 2021

E-cigarettes compromise the gut barrier and trigger inflammation.

iScience 2021 Feb 6;24(2):102035. Epub 2021 Jan 6.

Department of Pathology, University of California, San Diego, CA 92093, USA.

E-cigarette usage continues to rise, yet the safety of e-cigarette aerosols is questioned. Using murine models of acute and chronic e-cigarette aerosol inhalation, murine colon transcriptomics, and murine and human gut-derived organoids in co-culture models, we assessed the effects of e-cigarette use on the gut barrier. Histologic and transcriptome analyses revealed that chronic, but not acute, nicotine-free e-cigarette use increased inflammation and reduced expression of tight junction (TJ) markers. Exposure of murine and human enteroid-derived monolayers (EDMs) to nicotine-free e-cigarette aerosols alone or in co-culture with bacteria also causes barrier disruption, downregulation of TJ protein, and enhanced inflammation in response to infection. These data highlight the harmful effects of "non-nicotine" component of e-cigarettes on the gut barrier. Considering the importance of an intact gut barrier for host fitness and the impact of gut mucosal inflammation on a multitude of chronic diseases, these findings are broadly relevant to both medicine and public health.
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http://dx.doi.org/10.1016/j.isci.2021.102035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841355PMC
February 2021

Parental experiences of adolescent cancer-related distress: A qualitative study.

Eur J Cancer Care (Engl) 2021 Jan 29:e13417. Epub 2021 Jan 29.

Department of Psychology, University of Bath, Bath, UK.

Objective: Adolescents' cancer-related distress is more complex, severe, and long-lasting than that of children and adults. Parents adopt an active role in supporting their adolescent, reporting that adolescent cancer-related distress is the most problematic symptom parents experience. Research has predominantly focused on exploring adolescents' experiences of cancer-related distress, with little attention to how their parents experience their adolescent's cancer-related distress. Therefore, we aimed to explore parents' experiences of distress within the context of parenting an adolescent with cancer-related distress during or immediately subsequent to active treatment.

Methods: A total of 21 semi-structured interviews were conducted face-to-face or via telephone, with parents of adolescents aged 12-18 years from south-west England. Inductive reflexive thematic analysis was used to analyse the data.

Results: Three themes were generated: "The contagion of distress", "Navigating breaking point" and "Developmental disruption". Parental distress transcended from adolescent cancer-related distress, eliciting uncertainty and challenging parenting limits. Parental distress was perpetuated by feelings that their adolescent had missed out on "normal" adolescence during and just after active treatment.

Conclusion: Parental distress reflected the multi-faceted nature of their adolescent's cancer-related distress. Findings advocate the importance of providing a parental voice within adolescent oncology populations. Developing tailored interventions to address parental distress are suggested.
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http://dx.doi.org/10.1111/ecc.13417DOI Listing
January 2021

Halogen Radicals Contribute to the Halogenation and Degradation of Chemical Additives Used in Hydraulic Fracturing.

Environ Sci Technol 2021 Feb 15;55(3):1545-1554. Epub 2021 Jan 15.

Department of Energy, Environmental & Chemical Engineering, Washington University in St. Louis, St. Louis, Missouri 63130, United States.

In hydraulic fracturing fluids, the oxidant persulfate is used to generate sulfate radical to break down polymer-based gels. However, sulfate radical may be scavenged by high concentrations of halides in hydraulic fracturing fluids, producing halogen radicals (e.g., Cl, Cl, Br, Br, and BrCl). In this study, we investigated how halogen radicals alter the mechanisms and kinetics of the degradation of organic chemicals in hydraulic fracturing fluids. Using a radical scavenger (i.e., isopropanol), we determined that halogenated products of additives such as cinnamaldehyde (i.e., α-chlorocinnamaldehyde and α-bromocinnamaldehyde) and citrate (i.e., trihalomethanes) were generated via a pathway involving halogen radicals. We next investigated the impact of halogen radicals on cinnamaldehyde degradation rates. The conversion of sulfate radicals to halogen radicals may result in selective degradation of organic compounds. Surprisingly, we found that the addition of halides to convert sulfate radicals to halogen radicals did not result in selective degradation of cinnamaldehyde over other compounds (i.e., benzoate and guar), which may challenge the application of radical selectivity experiments to more complex molecules. Overall, we find that halogen radicals, known to react in advanced oxidative treatment and sunlight photochemistry, also contribute to the unintended degradation and halogenation of additives in hydraulic fracturing fluids.
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http://dx.doi.org/10.1021/acs.est.0c03685DOI Listing
February 2021

Acidic Calcium-Independent Phospholipase A2 Regulates Eosinophil-Mediated Pathology during Filarial Manifestation of Tropical Pulmonary Eosinophilia.

J Immunol 2021 Feb 13;206(4):722-736. Epub 2021 Jan 13.

Molecular Parasitology and Immunology Division, Council of Scientific and Industrial Research-Central Drug Research Institute, Lucknow 226031, India; and

Eosinophils mediate pathological manifestations during tropical pulmonary eosinophilia (TPE), a potentially fatal complication of lymphatic filariasis, by mechanisms that are incompletely understood. Using two-dimensional gel electrophoresis, mass spectrometry, flow cytometry, and pharmacological and functional studies, we identified acidic calcium-independent phospholipase A2 (aiPLA2) as the master regulator of TPE pathogenesis. FACS-sorted lung eosinophils from TPE mice exhibited aiPLA2-dependent activation characterized by heavy calcium influx, F-actin polymerization, increased degranulation, and heightened reactive oxygen species generation. Interestingly, aiPLA2 also promoted alternative activation in lung macrophages and regulated the release of inflammatory intermediates from them. Treatment of TPE mice with MJ33, a nontoxic pharmacological inhibitor of aiPLA2, lowered eosinophil counts in the bronchoalveolar lavage fluid, reduced eosinophil peroxidase and β-hexosaminidase activity, increased airway width, improved lung endothelial barrier, and lowered the production of inflammatory lipid intermediates, which significantly improved the pathological condition of the lungs. Importantly, ex vivo reconstitution of arachidonic acid to eosinophils from MJ33-treated TPE mice increased eosinophil degranulation and inflammatory lipid intermediates underlining the pivotal role of aiPLA2 in arachidonic acid metabolism. Mechanistically, phosphorylation of JNK-1 regulated phospholipase activity of aiPLA2, whereas IgG cross-linking mediated pathological activation of eosinophils. Taken together, ours is the first study, to our knowledge, to report hitherto undocumented role of aiPLA2 in regulating TPE pathogenesis.
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http://dx.doi.org/10.4049/jimmunol.2000604DOI Listing
February 2021

A call to action: why medical education curriculum needs to encourage young physicians to innovate.

Arch Dermatol Res 2021 Jan 12. Epub 2021 Jan 12.

Department of Dermatology, Harvard Medical School, Wellman Center for Photomedicine, Massachusetts General Hospital, 50 Blossom Street-Thier 2, Boston, MA, 02114, USA.

Patient-centered and physician-led innovations are key to promoting physicians as visionary leaders in the healthcare system especially during times of crises. COVID-19 has inspired some promising recent advancements within medicine worth noting, including improvements in telemedicine, 3-D printed personal protective equipment (PPE) and ventilators, drug and vaccine development, sterilization of PPE allowing for reuse, and point of care testing; they highlight a broader lesson for how we might innovate better within medicine, even after the crisis has passed. As such, with the complexities of modern-day medicine, to continue to foster this culture of innovation, it is paramount that going forward, medical education adapt and embrace an innovation curriculum that prepares physicians and healthcare workers to work with their communities and researchers to confidently tackle any challenges that may present. Integrating innovation into our careers and medical training is important for advancement of the field and to be able to handle challenges that may present to the healthcare system.
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http://dx.doi.org/10.1007/s00403-020-02180-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802405PMC
January 2021

A standardized polyherbal preparation POL-6 diminishes alcohol withdrawal anxiety by regulating Gabra1, Gabra2, Gabra3, Gabra4, Gabra5 gene expression of GABA receptor signaling pathway in rats.

BMC Complement Med Ther 2021 Jan 6;21(1):13. Epub 2021 Jan 6.

Department of Pharmacology, Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, Shri Vile Parle Kelavani Mandal's Narsee Monjee Institute of Management Studies University, Mumbai, Maharashtra, 400056, India.

Background: Alcohol abuse is a major problem worldwide and it affects people's health and economy. There is a relapse in alcohol intake due to alcohol withdrawal. Alcohol withdrawal anxiety-like behavior is a symptom that appears 6-24 h after the last alcohol ingestion.

Methods: The present study was designed to explore the protective effect of a standardized polyherbal preparation POL-6 in ethanol withdrawal anxiety in Wistar rats. POL-6 was prepared by mixing the dried extracts of six plants Bacopa monnieri, Hypericum perforatum, Centella asiatica, Withania somnifera, Camellia sinesis, and Ocimum sanctum in the proportion 2:1:2:2:1:2 respectively. POL-6 was subjected to phytochemical profiling through LC-MS, HPLC, and HPTLC. The effect of POL-6 on alcohol withdrawal anxiety was tested using a two-bottle choice drinking paradigm model giving animals' free choice between alcohol and water for 15 days. Alcohol was withdrawn on the 16th day and POL-6 (20, 50, and 100 mg/kg, oral), diazepam (2 mg/kg) treatment was given on the withdrawal days. Behavioral parameters were tested using EPM and LDT. On the 18th day blood was collected from the retro-orbital sinus of the rats and alcohol markers ALT, AST, ALP, and GGT were studied. At end of the study, animals were sacrificed and the brain was isolated for exploring the influences of POL-6 on the mRNA expression of GABA receptor subunits in the amygdala and hippocampus.

Results: Phytochemical profiling showed that POL-6 contains major phytoconstituents like withaferin A, quercetin, catechin, rutin, caeffic acid, and β-sitosterol. In-vivo studies showed that POL-6 possesses an antianxiety effect in alcohol withdrawal. Gene expression studies on the isolated brain tissues showed that POL-6 normalizes the GABAergic transmission in the amygdala and hippocampus of the rats.

Conclusion: The study concludes that POL-6 may have therapeutic potential for treating ethanol-type dependence.
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http://dx.doi.org/10.1186/s12906-020-03181-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789136PMC
January 2021

Male infertility due to testicular disorders.

J Clin Endocrinol Metab 2021 Jan;106(2):e442-e459

Section of Endocrinology and Investigative Medicine, Imperial College London, UK.

Context: Male infertility is defined as the inability to conceive following 1 year of regular unprotected intercourse. It is the causative factor in 50% of couples and a leading indication for assisted reproductive techniques (ART). Testicular failure is the most common cause of male infertility, yet the least studied to date.

Evidence Acquisition: The review is an evidence-based summary of male infertility due to testicular failure with a focus on etiology, clinical assessment, and current management approaches. PubMed-searched articles and relevant clinical guidelines were reviewed in detail.

Evidence Synthesis/results: Spermatogenesis is under multiple levels of regulation and novel molecular diagnostic tests of sperm function (reactive oxidative species and DNA fragmentation) have since been developed, and albeit currently remain as research tools. Several genetic, environmental, and lifestyle factors provoking testicular failure have been elucidated during the last decade; nevertheless, 40% of cases are idiopathic, with novel monogenic genes linked in the etiopathogenesis. Microsurgical testicular sperm extraction (micro-TESE) and hormonal stimulation with gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors are recently developed therapeutic approaches for men with the most severe form of testicular failure, nonobstructive azoospermia. However, high-quality clinical trials data is currently lacking.

Conclusions: Male infertility due to testicular failure has traditionally been viewed as unmodifiable. In the absence of effective pharmacological therapies, delivery of lifestyle advice is a potentially important treatment option. Future research efforts are needed to determine unidentified factors causative in "idiopathic" male infertility and long-term follow-up studies of babies conceived through ART.
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http://dx.doi.org/10.1210/clinem/dgaa781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823320PMC
January 2021

Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives.

Biomedicines 2020 Dec 6;8(12). Epub 2020 Dec 6.

Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania.

Withaferin A (WA), a manifold studied, C28-steroidal lactone withanolide found in . Given its unique beneficial effects, it has gathered attention in the era of modern science. Cancer, being considered a "hopeless case and the leading cause of death worldwide, and the available conventional therapies have many lacunae in the form of side effects. The poly pharmaceutical natural compound, WA treatment, displayed attenuation of various cancer hallmarks by altering oxidative stress, promoting apoptosis, and autophagy, inhibiting cell proliferation, reducing angiogenesis, and metastasis progression. The cellular proteins associated with antitumor pathways were also discussed. WA structural modifications attack multiple signal transduction pathways and enhance the therapeutic outcomes in various diseases. Moreover, it has shown validated pharmacological effects against multiple neurodegenerative diseases by inhibiting acetylcholesterinases and butyrylcholinesterases enzyme activity, antidiabetic activity by upregulating adiponectin and preventing the phosphorylation of peroxisome proliferator-activated receptors (PPARγ), cardioprotective activity by AMP-activated protein kinase (AMPK) activation and suppressing mitochondrial apoptosis. The current review is an extensive survey of various WA associated disease targets, its pharmacokinetics, synergistic combination, modifications, and biological activities.
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http://dx.doi.org/10.3390/biomedicines8120571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762146PMC
December 2020

Polyhydroxyalkanoate synthesis and characterization: A proteogenomic and process optimization study for biovalorization of industrial lignin.

Bioresour Technol 2021 Jan 23;320(Pt B):124439. Epub 2020 Nov 23.

School of Environmental Sciences, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address:

The strain Burkholderia sp. ISTR5 (R5) was studied for polyhydroxyalkanoate (PHA) production on Kraft lignin (KL) and lignosulfonate (LS) as substrates. During the initial screening, the maximum PHA mass fraction in biomass produced on KL and LS was 23% and 18%, respectively, at 96 h. PHA production on KL was further optimized using the Box-Behnken Design (BBD) model of Response Surface Methodology (RSM). After optimization, a 42.5% increase in PHA production and a 32.2% increase in the total cell biomass was observed. PHA was characterized by GC-MS, TEM, FTIR, NMR, and fluorescence microscopy. It was found to be a small chain length PHA with a copolymer of poly (hydroxybutyrate-co-hydroxyvalerate) (PHBV). The degradation of PHBV was also studied using this strain; it was observed that R5 completely degraded PHBV in 120 h. Genomic and proteomic analysis of R5 revealed numerous enzymes for the metabolism of lignin degradation and PHA production.
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http://dx.doi.org/10.1016/j.biortech.2020.124439DOI Listing
January 2021

Transcriptomic response of Gordonia sp. strain NB4-1Y when provided with 6:2 fluorotelomer sulfonamidoalkyl betaine or 6:2 fluorotelomer sulfonate as sole sulfur source.

Biodegradation 2020 12 5;31(4-6):407-422. Epub 2020 Nov 5.

Department of Biological Sciences, Thompson Rivers University, Kamloops, BC, V2C 0C8, Canada.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are environmental contaminants of concern. We previously described biodegradation of two PFAS that represent components and transformation products of aqueous film-forming foams (AFFF), 6:2 fluorotelomer sulfonamidoalkyl betaine (6:2 FTAB) and 6:2 fluorotelomer sulfonate (6:2 FTSA), by Gordonia sp. strain NB4-1Y. To identify genes involved in the breakdown of these compounds, the transcriptomic response of NB4-1Y was examined when grown on 6:2 FTAB, 6:2 FTSA, a non-fluorinated analog of 6:2 FTSA (1-octanesulfonate), or MgSO, as sole sulfur source. Differentially expressed genes were identified as those with ± 1.5 log-fold-differences (± 1.5 logFD) in transcript abundances in pairwise comparisons. Transcriptomes of cells grown on 6:2 FTAB and 6:2 FTSA were most similar (7.9% of genes expressed ± 1.5 logFD); however, several genes that were expressed in greater abundance in 6:2 FTAB treated cells compared to 6:2 FTSA treated cells were noted for their potential role in carbon-nitrogen bond cleavage in 6:2 FTAB. Responses to sulfur limitation were observed in 6:2 FTAB, 6:2 FTSA, and 1-octanesulfonate treatments, as 20 genes relating to global sulfate stress response were more highly expressed under these conditions compared to the MgSO treatment. More highly expressed oxygenase genes in 6:2 FTAB, 6:2 FTSA, and 1-octanesulfonate treatments were found to code for proteins with lower percent sulfur-containing amino acids compared to both the total proteome and to oxygenases showing decreased expression. This work identifies genetic targets for further characterization and will inform studies aimed at evaluating the biodegradation potential of environmental samples through applied genomics.
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http://dx.doi.org/10.1007/s10532-020-09917-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661421PMC
December 2020

Parental Experiences of Adolescent Cancer-Related Fatigue: A Qualitative Study.

J Pediatr Psychol 2020 11;45(10):1093-1102

Department of Psychology, University of Bath.

Objective: Cancer-related fatigue is common, disabling, and chronic, but professional help is not necessarily sought. Parents can support symptom management and facilitate help-seeking. This study explored parental experiences of their adolescent's cancer-related fatigue and what they do to help.

Methods: Qualitative semi-structured interviews were conducted with 21 parents of 17 adolescents aged 12-18 who were previously diagnosed with cancer. Reflexive thematic analysis was used to analyze the data.

Results: Three high-order themes were generated. Firstly, "fatigue is inevitable and unpredictable." This encompassed parental perceptions of fatigue as variable, distinct from normal tiredness, and linked to sleep and mood. Fatigue was seen as arising from cancer, which rendered parents helpless. Secondly, "fatigue is disruptive to normal life" beyond cancer treatment, which is contrary to expectations. Thirdly, parents managed fatigue by trying to balance the adolescent's desires for normality and their own perception of what is realistic with encouraging activities, and by seeking support from others.

Conclusions: Parents see adolescent cancer-related fatigue as multi-faceted and experience it as unpredictable and attributed to cancer. They struggle to distinguish normal adolescent behavior from problematic fatigue, and to balance supporting and empowering the adolescent to live life to the fullest whilst also being realistic about the limitations imposed by fatigue and the benefits of activity. Parents try to manage fatigue practically but want more information about adolescent cancer-related fatigue to help establish their own and their adolescent's expectations.
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http://dx.doi.org/10.1093/jpepsy/jsaa080DOI Listing
November 2020

Clinical deterioration during neutropenia recovery after G-CSF therapy in patient with COVID-19.

Respir Med Case Rep 2020 24;31:101231. Epub 2020 Sep 24.

Department of Pulmonary Critical Care & Sleep Division, Wayne State University, Harper University Hospital 3990 John R - 3 Hudson Detroit, MI, 48201, USA.

Background: Granulocyte colony stimulating factors (G-CSFs) induce neutrophils proliferation and cytokines production. It has often been used to treat neutropenia without solid evidence of efficacy. It has been demonstrated that respiratory distress is associated with neutropenia recovery but not with G-CSFs. In general, G-CSFs are known to be safe and well tolerated in most clinical settings. However, the safety of G-CSFs in an overwhelming inflammatory disease like coronavirus disease 2019 (COVID-19) is largely unknown.

Case Summary: We report a case with COVID-19 and neutropenia who rapidly deteriorated after administration of G-CSF.

Conclusion: We observed a faster neutropenia recovery than previously known after administration of G-CSF in our case and in three similar cases previously reported in literature. This rapid neutropenia recovery and the robust inflammatory response in COVID-19 raise concerns about G-CSF safety in patients with COVID-19.
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http://dx.doi.org/10.1016/j.rmcr.2020.101231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515585PMC
September 2020

Statistical interpretation of environmental influencing parameters on COVID-19 during the lockdown in Delhi, India.

Environ Dev Sustain 2020 Sep 25:1-14. Epub 2020 Sep 25.

Department of Nanotechnology, Sri Guru Granth Sahib World University Fatehgarh Sahib, Fatehgarh Sahib, Punjab India.

The novel coronavirus disease is known as COVID-19, which is declared as a pandemic by the World Health Organization during March 2020. In this study, the COVID-19 connection with various weather parameters like temperature, wind speed, and relative humidity is investigated and the future scenario of COVID-19 is predicted based on the Gaussian model (GM). This study is conducted in Delhi, the capital city of India, during the lowest mobility rate due to strict lockdown nationwide for about two months from March 15 to May 17, 2020. Spearman correlation is applied to obtain the interconnection of COVID-19 cases with weather parameters. Based on statistical analysis, this has been observed that the temperature parameter shows a significant positive trend during the period of study. The number of confirmed cases of COVID-19 is fitted with respect to the number of days by using the Gaussian curve and it is estimated on the basis of the model that maximum cases will go up to 123,886 in number. The maximum number of cases will be observed during the range of 166 ± 36 days. It is also estimated by using the width of the fitted GM that it will take minimum of 10 months for the complete recovery from COVID-19. Additionally, the linear regression technique is used to find the trend of COVID-19 cases with temperature and it is estimated that with an increase in temperature by 1 °C, 30 new COVID-19 cases on daily basis will be expected to observe. This study is believed to be a preliminary study and to better understand the concrete relationship of coronavirus, at least one complete cycle is essential to investigate. The laboratory-based study is essential to be done to support the present field-based study. Henceforth, based on preliminary studies, significant inputs are put forth to the research community and government to formulate thoughtful strategies like medical facilities such as ventilators, beds, testing centers, quarantine centers, etc., to curb the effects of COVID-19.
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http://dx.doi.org/10.1007/s10668-020-01000-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515685PMC
September 2020

Relapse of Plasmablastic Lymphoma With Cutaneous Involvement in an Immunocompetent Male.

Ear Nose Throat J 2020 Sep 21:145561320952190. Epub 2020 Sep 21.

Department of Dermatology, University of California, Irvine, Irvine, CA, USA.

Plasmablastic lymphoma (PBL) is a rare type of non-Hodgkin lymphoma frequently found in the context of immunosuppression and infection with human immunodeficiency virus (HIV) and/or Epstein-Barr virus (EBV). A 33-year-old immunocompetent male presented with recurrent episodes of epistaxis and a growing intranasal mass. Excisional biopsy of the mass revealed an immunohistochemical profile diagnostic of PBL. Upon completion of chemoradiation, he underwent a transnasal endoscopic mucosal flap tissue rearrangement to restore patency for both functional and surveillance purposes. There was no endoscopic evidence of residual or recurrent disease. However, 8 months later, he was found to have a relapse involving the skin. The nasal cavity is one of the most common sites affected by PBL. Involvement of the nasal cavity may present with symptoms of persistent epistaxis accompanied by an enlarging mass. A plasmablastic immunophenotype in combination with HIV or EBV positivity can aid diagnosis.
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http://dx.doi.org/10.1177/0145561320952190DOI Listing
September 2020

Molecular Signaling Pathways and Essential Metabolic Elements in Bone Remodeling: An Implication of Therapeutic Targets for Bone Diseases.

Curr Drug Targets 2021 ;22(1):77-104

School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, 173212, India.

Bone is one of the dynamic tissues in the human body that undergoes continuous remodelling through subsequent actions of bone cells, osteoclasts, and osteoblasts. Several signal transduction pathways are involved in the transition of mesenchymal stem cells into osteoblasts. These primarily include Runx2, ATF4, Wnt signaling and sympathetic signalling. The differentiation of osteoclasts is controlled by M-CSF, RANKL, and costimulatory signalling. It is well known that bone remodelling is regulated through receptor activator of nuclear factor-kappa B ligand followed by binding to RANK, which eventually induces the differentiation of osteoclasts. The resorbing osteoclasts secrete TRAP, cathepsin K, MMP-9 and gelatinase to digest the proteinaceous matrix of type I collagen and form a saucer-shaped lacuna along with resorption tunnels in the trabecular bone. Osteoblasts secrete a soluble decoy receptor, osteoprotegerin that prevents the binding of RANK/RANKL and thus moderating osteoclastogenesis. Moreover, bone homeostasis is also regulated by several growth factors like, cytokines, calciotropic hormones, parathyroid hormone and sex steroids. The current review presents a correlation of the probable molecular targets underlying the regulation of bone mass and the role of essential metabolic elements in bone remodelling. Targeting these signaling pathways may help to design newer therapies for treating bone diseases.
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http://dx.doi.org/10.2174/1389450121666200910160404DOI Listing
January 2021

Antimicrobial flavonoids as a potential substitute for overcoming antimicrobial resistance.

Fitoterapia 2020 Oct 7;146:104720. Epub 2020 Sep 7.

Laboratory of Natural Products, Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda, Punjab 151001, India.. Electronic address:

Background: Infectious diseases are the leading cause of death in 21 century due to antimicrobial resistance and scarcity of new molecules to undertake rising infections. There could be a multiple reasons behind antimicrobial resistance whether it is increased drug metabolism or bacterial endotoxins. The demand of effective medication is increasing day by day to treat microbial infections and combat antimicrobial resistance. In recent years most of the synthetic antimicrobials developed resistance so natural products could provide better options to fulfill this demand. There has been increasing interest in the research on flavonoids because various flavonoids were found to be effective against pathogenic microorganisms.

Objective: The objective of this article will be to explore antimicrobial activity of flavonoids with special focus on their possible mechanism of action.

Methods: The article reviewed recent literature related to flavonoids with antimicrobial activity, which were isolated from various sources and the compounds showing fairly good activity against tested microbial species were discussed.

Results: By throughout literature review it has been found that flavonoids show antimicrobial effect by inhibiting virulence factors, efflux pump, biofilm formation, membrane disruption, cell envelop synthesis, nucleic acid synthesis, and bacterial motility inhibition.

Conclusion: Most of the antimicrobial drugs available now a days are ineffective due to development of resistance to them. Flavonoids have the potential to overcome this emerging crisis as this class of natural products showed the antimicrobial activity by different mechanisms than those of conventional drugs, so flavonoid could be an effective treatment of pathogenic infections.
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http://dx.doi.org/10.1016/j.fitote.2020.104720DOI Listing
October 2020

Baseline levels of seminal reactive oxygen species predict improvements in sperm function following antioxidant therapy in men with infertility.

Clin Endocrinol (Oxf) 2021 Jan 12;94(1):102-110. Epub 2020 Oct 12.

Department of Andrology, Hammersmith Hospital, London, UK.

Background: Poor sperm function is a major cause of infertility. There is no drug therapy to improve sperm function. Semen oxidative stress is a recently identified pathway for sperm damage. Commercial antioxidants such as L-carnitine and acetyl-L-carnitine (LAL) are commonly self-administered by infertile men. However, concerns have been raised whether inappropriate LAL therapy causes reductive stress-mediated sperm damage. It is imperative to investigate whether: (1) LAL improves sperm function by reducing reactive oxidative species (ROS); (2) LAL has differential effects on sperm function between men with normal and elevated ROS.

Methods: A prospective cohort study of routine clinical practice was performed in infertile men with abnormal sperm quality. Changes in sperm function and semen ROS levels following three months of oral LAL therapy were compared between participants with baseline seminal normal ROS (≤10RLU/SEC/10 sperm; n = 29) and High ROS (>10 RLU/SEC/10 sperm; n = 15) levels measured using an established colorimetric-luminol method.

Results: In normal ROS group, sperm function did not change following LAL therapy. In high ROS group, LAL therapy reduced semen ROS fivefold, increased sperm count by 50% (mean count in mill/ml: 21.5 + 7.2, baseline; 32.6 + 9.5, post-treatment, P = .0005), and total and progressive sperm motility each by 30% (mean total sperm motility in % 29.8 + 5.0, baseline: 39.4 + 6.2, post-treatment, P = .004; mean progressive sperm motility in % 23.1 + 4.6, baseline: 30.0 + 5.5, post-treatment, P = .014 vs. baseline).

Conclusions: We report for the first time that LAL only improves sperm quality in infertile men who have baseline high-ROS levels prior to treatment. These data have important potential implications for couples with male infertility and their clinicians.
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http://dx.doi.org/10.1111/cen.14328DOI Listing
January 2021

The DNA Glycosylase NEIL2 Suppresses -Infection-Induced Inflammation and DNA Damage in Colonic Epithelial Cells.

Cells 2020 08 28;9(9). Epub 2020 Aug 28.

Department of Pathology, University of California, San Diego, CA 92093, USA.

Colorectal cancer (CRC) is the third most prevalent cancer, while the majority (80-85%) of CRCs are sporadic and are microsatellite stable (MSS), and approximately 15-20% of them display microsatellite instability (MSI). Infection and chronic inflammation are known to induce DNA damage in host tissues and can lead to oncogenic transformation of cells, but the role of DNA repair proteins in microbe-associated CRCs remains unknown. Using CRC-associated microbes such as () in a coculture with murine and human enteroid-derived monolayers (EDMs), here, we show that, among all the key DNA repair proteins, NEIL2, an oxidized base-specific DNA glycosylase, is significantly downregulated after infection. infection of NEIL2-null mouse-derived EDMs showed a significantly higher level of DNA damage, including double-strand breaks and inflammatory cytokines. Several CRC-associated microbes, but not the commensal bacteria, induced the accumulation of DNA damage in EDMs derived from a murine CRC model, and had the most pronounced effect. An analysis of publicly available transcriptomic datasets showed that the downregulation of NEIL2 is often encountered in MSS compared to MSI CRCs. We conclude that the CRC-associated microbe induced the downregulation of NEIL2 and consequent accumulation of DNA damage and played critical roles in the progression of CRCs.
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http://dx.doi.org/10.3390/cells9091980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565382PMC
August 2020