Publications by authors named "Hussain Arif"

225 Publications

Managing critical care during COVID-19 pandemic: The experience of an ICU of a tertiary care hospital.

J Infect Public Health 2021 Sep 30;14(11):1635-1641. Epub 2021 Sep 30.

College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Intensive Care Department, King Abdulaziz Medical City, Ministry of National Guard - Health Affairs, Riyadh, Saudi Arabia. Electronic address:

Background: The COVID-19 pandemic has strained ICUs worldwide. To learn from our experience, we described the critical care response to the outbreak.

Methods: This is a case study of the response of the Intensive Care Department (75-bed capacity) at a tertiary-care hospital to COVID-19 pandemic, which resulted in a high number of critically ill patients.

Results: Between March 1 and July 31, 2020, 822 patients were admitted to the adult non-cardiac ICUs with suspected (72%)/confirmed (38%) COVID-19. At the peak of the surge, 125 critically ill patients with COVID-19 were managed on single day. To accommodate these numbers, the bed capacity of 4 ICUs was increased internally from 58 to 71 beds (+40%) by cohorting 2 patients/room in selected rooms; forty additional ICUs beds were created in 2 general wards; one cardiac ICU was converted to managed non-COVID-19 general ICU patients and one ward was used as a stepdown for COVID-19 patients. To manage respiratory failure, 53 new ICU ventilators, 90 helmets for non-invasive ventilation and 47 high-flow nasal cannula machines were added to the existing capacity. Dedicated medical teams cared for the COVID-19 patients to prevent cross-contamination. The nurse-to-patient and RT-to-patient ratio remained mostly 1:1 and 1:6, respectively. One-hundred-ten ward nurses were up-skilled to care for COVID-19 and other ICU patients using tiered staffing model. Daily executive rounds were conducted to identify patients for transfer and at least 10 beds were made available for new COVID-19 admissions/day. The consumption of PPE increased multiple fold compared with the period preceding the pandemic. Regular family visits were not allowed and families were updated daily by videoconferencing and phone calls.

Conclusions: Our ICU response to the COVID-19 pandemic required almost doubling ICU bed capacity and changing multiple aspects of ICU workflow to be able to care for high numbers of affected patients.
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http://dx.doi.org/10.1016/j.jiph.2021.09.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481117PMC
September 2021

Dynamic right-to-left interatrial shunt may complicate severe COVID-19.

BMJ Case Rep 2021 Oct 1;14(10). Epub 2021 Oct 1.

Department of Anesthesia and Intensive Care, Cardiocentro Ticino, Lugano, Switzerland.

Right-to-left (RTL) interatrial shunt (IAS) may complicate select cases of COVID-19 pneumonia. We describe the use of serial imaging to monitor shunt in critically ill patients. A 52-year-old man presented with COVID-19 pneumonia. Hypoxia worsened despite maximal medical therapy and non-invasive ventilation. On day 8, saline microbubble contrast-enhanced transthoracic echocardiography revealed a patent foramen ovale (PFO) with RTLIAS. Invasive ventilation was initiated the next day. The course was complicated by intermittent severe desaturation without worsening aeration or haemodynamic instability, so PFO closure was considered. However, on day 12, saline microbubble contrast-enhanced transoesophageal echocardiography excluded RTLIAS. The patient was extubated on day 27 and discharged home 12 days later. Thus, RTLIAS may be dynamic and changes can be detected and monitored by serial imaging. Bedside echocardiography with saline microbubble contrast, a simple, minimally invasive bedside test, may be useful in the management of patients with severe hypoxia.
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http://dx.doi.org/10.1136/bcr-2021-245301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488708PMC
October 2021

Response to rucaparib in BRCA-mutant metastatic castration-resistant prostate cancer identified by genomic testing in the TRITON2 study.

Clin Cancer Res 2021 Oct 1. Epub 2021 Oct 1.

Medicine, Memorial Sloan Kettering Cancer Center

Purpose: The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is approved in the US for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic or (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA+), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in BRCA+ mCRPC patients identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2.

Experimental Design: Patients had progressed after next-generation androgen receptor-directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized.

Results: TRITON2 enrolled 115 BRCA+ patients identified by central plasma (n = 34), central tissue (n = 37), or local (n = 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the three assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different to patients identified as BRCA+ by tissue testing.

Conclusion: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA+ mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-2199DOI Listing
October 2021

Severe COVID-19 pneumonia complicated by cardiomyopathy and a small anterior pneumothorax.

BMJ Case Rep 2021 Sep 21;14(9). Epub 2021 Sep 21.

Department of Cardiovascular Sciences, King Abdulaziz Medical City, Riyadh, Al Riyadh Province, Saudi Arabia.

Although, cardiac injury, pneumothorax and pneumomediastinum are associated with COVID-19, differentiation of their symptoms and signs from those of COVID-19 itself is challenging. Without a high index of suspicion, cardiomyopathy and anterior pneumothorax are easily missed. These complications may be underdiagnosed in patients with COVID-19. Cardiomyopathy and pneumothorax may cause or exacerbate respiratory failure. If their management is delayed, cardiac arrest can occur. To increase the awareness of these issues, we describe the course and imaging of a 39-year-old woman with severe COVID-19 who developed cardiomyopathy and a small anterior pneumothorax with pneumomediastinum. Transthoracic echocardiography is technically challenging in the presence of anterior pneumothorax. Furthermore, although CT is the gold standard for the diagnosis of pneumothorax, this is not always feasible in critically ill patients. Lateral decubitus chest X-rays and lung ultrasound may facilitate the diagnosis of pneumothorax at the bedside of patients with COVID-19.
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http://dx.doi.org/10.1136/bcr-2021-245900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458345PMC
September 2021

Does tourism increase CO emissions and health spending in Mexico? New evidence from nonlinear ARDL approach.

Int J Health Plann Manage 2021 Sep 17. Epub 2021 Sep 17.

College of Business Administration, Liaoning Technical University, XingCheng, China.

This study investigates the nexus between tourism, CO emissions and health spending in Mexico. We applied a nonlinear ARDL approach for the empirical analysis for the time period 1996-2018. Mexico receives a large number of tourists each year, tourism improves foreign exchange earnings and contributes positively to the economic growth. However, tourist activities impose a serious environmental cost in terms of CO emissions which increase health spending. The empirical findings suggest that tourism leads to CO emissions which resultantly causes a high level of health spending in Mexico. Both short-run and long-run findings reported a significant positive association between tourism, CO emissions, and health expenditures. Therefore, the government needs legislation to reduce CO emissions, besides the use of renewable energy could also help to reduce the CO emissions and health expenditures in society. This study does not support to reduce the health expenditure, rather it suggests optimal utilization of the funds allocated to the health sector.
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http://dx.doi.org/10.1002/hpm.3322DOI Listing
September 2021

A Prospective Multicenter Evaluation of Initial Treatment Choice in Metastatic Renal Cell Carcinoma Prior to the Immunotherapy Era: The MaRCC Registry Experience.

Clin Genitourin Cancer 2021 Jul 10. Epub 2021 Jul 10.

Duke University Medical Center, Durham, NC.

Introduction: The Metastatic Renal Cell Carcinoma (MaRCC) Registry provides prospective data on real-world treatment patterns and outcomes in patients with metastatic renal cell carcinoma (mRCC).

Methods And Materials: Patients with mRCC and no prior systemic therapy were enrolled at academic and community sites. End of study data collection was in March 2019. Outcomes included overall survival (OS). A survey of treating physicians assessed reasons for treatment initiations and discontinuations.

Results: Overall, 376 patients with mRCC initiated first-line therapy; 171 (45.5%) received pazopanib, 75 (19.9%) sunitinib, and 74 (19.7%) participated in a clinical trial. Median (95% confidence interval) OS was longest in the clinical trial group (50.3 [35.8-not reached] months) versus pazopanib (39.0 [29.7-50.9] months) and sunitinib 26.2 [19.9-61.5] months). Non-clear cell RCC (21.5% of patients) was associated with worse median OS than clear cell RCC (18.0 vs. 47.3 months). Differences in baseline characteristics, treatment starting dose, and relative dose exposure among treatment groups suggest selection bias. Survey results revealed a de-emphasis on quality of life, toxicity, and patient preference compared with efficacy in treatment selection.

Conclusion: The MaRCC Registry gives insights into real-world first-line treatment selection, outcomes, and physician rationale regarding initial treatment selection prior to the immunotherapy era. Differences in outcomes between clinical trial and off-study patients reflect the difficulty in translating trial results to real-world patients, and emphasize the need to broaden clinical trial eligibility. Physician emphasis on efficacy over quality of life and toxicity suggests more data and education are needed regarding these endpoints.
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http://dx.doi.org/10.1016/j.clgc.2021.07.002DOI Listing
July 2021

Microbial dysbiosis and epigenetics modulation in cancer development - A chemopreventive approach.

Semin Cancer Biol 2021 Jun 30. Epub 2021 Jun 30.

Centre of Advanced Study in Botany, Banaras Hindu University, Varanasi, 221005, India.

An overwhelming number of research articles have reported a strong relationship of the microbiome with cancer. Microbes have been observed more commonly in the body fluids like urine, stool, mucus of people with cancer compared to the healthy controls. The microbiota is responsible for both progression and suppression activities of various diseases. Thus, to maintain healthy human physiology, host and microbiota relationship should be in a balanced state. Any disturbance in this equilibrium, referred as microbiome dysbiosis becomes a prime cause for the human body to become more prone to immunodeficiency and cancer. It is well established that some of these microbes are the causative agents, whereas others may encourage the formation of tumours, but very little is known about how these microbial communications causing change at gene and epigenome level and trigger as well as encourage the tumour growth. Various studies have reported that microbes in the gut influence DNA methylation, DNA repair and DNA damage. The genes and pathways that are altered by gut microbes are also associated with cancer advancement, predominantly those implicated in cell growth and cell signalling pathways. This study exhaustively reviews the current research advancements in understanding of dysbiosis linked with colon, lung, ovarian, breast cancers and insights into the potential molecular targets of the microbiome promoting carcinogenesis, the epigenetic alterations of various potential targets by altered microbiota, as well as the role of various chemopreventive agents for timely prevention and customized treatment against various types of cancers.
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http://dx.doi.org/10.1016/j.semcancer.2021.06.024DOI Listing
June 2021

Antineoplastic action of sulforaphane on HeLa cells by modulation of signaling pathways and epigenetic pathways.

Minerva Med 2021 06 11. Epub 2021 Jun 11.

Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia.

Background: Epigenetic modifications alter signaling and molecular pathways and are an important therapeutic target. This study examined the effect of sulforaphane on molecular targets in HeLa cells.

Methods: Quantitative PCR of various molecular targets was performed. Activity of epigenetic enzymes was measured by ELISA and molecular docking analysis was conducted. Promoter methylation of some tumour suppressor genes was quantified using PCR based methylation array. In-silico protein-protein interaction network analysis was performed to understand the effect of transcriptional changes.

Results: Quantitative PCR demonstrated the transcriptional modulation of genes involved in proliferation, metastasis, inflammation, signal transduction pathways and chromatin modifiers. Sulforaphane reduced the enzymatic activity of DNA methyl transferases, histone deacetylases and histone methyltransferases. Molecular docking results suggest that sulforaphane competitively inhibited several DNA methyl transferases and histone deacetylases. Promoter 5'CpG methylation levels of selected tumour suppressor genes was found to be reduced which correlated with their transcriptional increase as well modulation of epigenetic enzymes. Further, protein-protein interaction network analysis discerned the participation of genes towards cancer pathways. Functional enrichment and pathway-based analysis represented the modulation of epigenetic and signaling pathways on sulforaphane treatment.

Conclusions: The modulation in transcriptional status of epigenetic regulators, genes involved in tumorigenesis resulting in tumour suppressor genes demethylation and re-expression underscores the mechanism behind the anti-cancer effect of sulforaphane on HeLa cells.
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http://dx.doi.org/10.23736/S0026-4806.21.07656-4DOI Listing
June 2021

Effect of host plant on cornucopia of mango fruit flies (Diptera: Tephritidae) and their triumphant management in context of climate change.

Saudi J Biol Sci 2021 Apr 19;28(4):2366-2373. Epub 2021 Feb 19.

Department Soil & Environmental Sciences, Muhammad Nawaz Sharif University of Agriculture Multan, Pakistan.

A study was performed to assess the preference of fourteen mango cultivars for fruit flies and their management by bagging. So the choice of Tephritid flies to mango cultivars during fruiting phase is crucial. Fourteen different cultivars of mango viz., 'Dusehri', 'Malda', 'Langra' early cultivars, 'Chaunsa', 'Fajri Klan', 'Sensation' medium whereas 'Sanglakhi', 'Retaul-12', 'Mehmood Khan', 'Tukhmi', 'Kala Chaunsa', 'Chitta Chaunsa', 'Dai Wala' and 'Sobey De Ting' late cultivars were assessed for their suitability for fruit flies. The results indicate that the population density of fruit flies was higher on late cultivars like 'Sanglakhi' (20.61 percent), 'Mehmood Khan' (20.22 percent) and 'Reutal-12' (19.92 percent) were proved to be highly susceptible to fruit flies. Among these the cultivar 'Reutal-12' was selected being commercial and future cultivar for the management of fruit flies through bagging. The results reported that the attack of tephritid fruit flies and other insect pests were zero in bagged fruits as compared with control. It was further recorded that the bagged fruits has maximum average fruit weight i.e. 203.50 and 197.83 g per fruit was noted in those treatments where butter paper bag and brown paper bag was wrapped with better coloration as compared with un-bagged fruit with 159.5 g per fruit. Similarly, on an average fruit length were more i.e. 90.17, 91.33 mm in bagged fruit and 85.33 in un-bagged fruits. Furthermore, bagged fruits have zero incidence of disease with reduced fruit crack, fruit sunburn, mechanical damage, bird damage, fruit blemished and agrochemical residues on the fruit. So, it is concluded that the special attention should be given on 'Reutal-12' for the management of fruit flies when devising an IPM program for the control of fruit flies. Further, bagging has proved to be the good agricultural practices for the production of quality mango.
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http://dx.doi.org/10.1016/j.sjbs.2021.01.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071905PMC
April 2021

A survey demonstrating that the procedural experience of residents in internal medicine, critical care and emergency medicine is poor: training in ultrasound is required to rectify this.

Ultrasound J 2021 Apr 13;13(1):20. Epub 2021 Apr 13.

Department of Cardiac Sciences, King Abdulaziz Medical City, King Abdulaziz International Medical Research Center, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia.

Background: Training in procedural skills is often suboptimal. The aim of this study was to quantify the needs of residents in internal medicine (IM), critical care (CC), and emergency medicine (EM) for instruction in ultrasound-guided procedures.

Methods: All IM, EM and CC residents (n = 200) at King Abdulaziz Medical City, Riyadh, Saudi Arabia, were invited to participate in a questionnaire-based survey to identify skill and experience gaps. The contribution of procedural skills to patient care (i.e. applicability) and proficiency in the sterile technique required to perform ultrasound-guided procedures were rated on Likert scales. Data on training, accreditation, and experience with and without ultrasound were collected.

Results: The overall response rate was 72% (IM 91%, CC 100%, EM 40%). Although the sample reported that procedural skills were very applicable, 19% (IM n = 25, EM n = 2) had not performed any procedures. However, five residents were accredited in point-of-care ultrasound, 61% of the sample had performed ultrasound-guided procedures and 65% had used landmark techniques. Whilst more internists had performed procedures using landmark techniques, CC and EM residents had performed more ultrasound-guided procedures. Whilst CC residents had not missed any opportunities to perform procedures because supervisors were less available, EM (6) and IM (89) residents had. Whilst skill gaps were only identified in the IM residency programme, experience gaps were present in all three residency programmes. The IM residency programme had larger experience gaps than the CC and EM programmes for all procedural skills.

Discussion: Residents in IM, CC and EM perceive that ultrasound-guided procedures are relevant to their practice. However, the IM residents performed fewer procedures than CC residents and EM residents at least partly because internists also lack skills in ultrasound. Training in ultrasound-guided procedures may reduce the use of landmark techniques and improve patient safety. Residents in IM, CC and EM therefore require training in ultrasound-guided procedures.
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http://dx.doi.org/10.1186/s13089-021-00221-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044269PMC
April 2021

Active surveillance of metastatic renal cell carcinoma: Results from a prospective observational study (MaRCC).

Cancer 2021 Jul 25;127(13):2204-2212. Epub 2021 Mar 25.

Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.

Background: Systemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow-growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature.

Methods: This was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient-related outcomes. Wilcoxon 2-sample rank-sum tests and χ tests were used to assess differences between ST and AS cohorts in continuous and categorical variables, respectively. Kaplan-Meier survival curves were used to assess survival.

Results: Of 504 patients, mRCC was initially managed by AS (n = 143) or ST (n = 305); 56 patients were excluded from the analysis. Disease was present in 69% of patients who received AS, whereas the remaining 31% had no evidence of disease. At data cutoff, 72 of 143 patients (50%) in the AS cohort had not received ST. The median overall survival was not reached (95% CI, 122 months to not estimable) in patients who received AS versus 30 months (95% CI, 25-44 months) in those who received ST. Quality of life at baseline was significantly better in patients who were managed with AS versus ST.

Conclusions: AS occurs frequently (32%) in real-world clinical practice and appears to be a safe and appropriate alternative to immediate ST in selected patients.
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http://dx.doi.org/10.1002/cncr.33494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251950PMC
July 2021

TRANSFORMER: A Randomized Phase II Study Comparing Bipolar Androgen Therapy Versus Enzalutamide in Asymptomatic Men With Castration-Resistant Metastatic Prostate Cancer.

J Clin Oncol 2021 04 22;39(12):1371-1382. Epub 2021 Feb 22.

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.

Purpose: Prostate cancer (PCa) becomes resistant to androgen ablation through adaptive upregulation of the androgen receptor in response to the low-testosterone microenvironment. Bipolar androgen therapy (BAT), defined as rapid cycling between high and low serum testosterone, disrupts this adaptive regulation in castration-resistant PCa (CRPC).

Methods: The TRANSFORMER (Testosterone Revival Abolishes Negative Symptoms, Fosters Objective Response and Modulates Enzalutamide Resistance) study is a randomized study comparing monthly BAT (n = 94) with enzalutamide (n = 101). The primary end point was clinical or radiographic progression-free survival (PFS); crossover was permitted at progression. Secondary end points included overall survival (OS), prostate-specific antigen (PSA) and objective response rates, PFS from randomization through crossover (PFS2), safety, and quality of life (QoL).

Results: The PFS was 5.7 months for both arms (hazard ratio [HR], 1.14; 95% CI, 0.83 to 1.55; = .42). For BAT, 50% decline in PSA (PSA50) was 28.2% of patients versus 25.3% for enzalutamide. At crossover, PSA50 response occurred in 77.8% of patients crossing to enzalutamide and 23.4% to BAT. The PSA-PFS for enzalutamide increased from 3.8 months after abiraterone to 10.9 months after BAT. The PFS2 for BAT→enzalutamide was 28.2 versus 19.6 months for enzalutamide→BAT (HR, 0.44; 95% CI, 0.22 to 0.88; = .02). OS was 32.9 months for BAT versus 29.0 months for enzalutamide (HR, 0.95; 95% CI, 0.66 to 1.39; = .80). OS was 37.1 months for patients crossing from BAT to enzalutamide versus 30.2 months for the opposite sequence (HR, 0.68; 95% CI, 0.36 to 1.28; = .225). BAT adverse events were primarily grade 1-2. Patient-reported QoL consistently favored BAT.

Conclusion: This randomized trial establishes meaningful clinical activity and safety of BAT and supports additional study to determine its optimal clinical integration. BAT can sensitize CRPC to subsequent antiandrogen therapy. Further study is required to confirm whether sequential therapy with BAT and enzalutamide can improve survival in men with CRPC.
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http://dx.doi.org/10.1200/JCO.20.02759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274807PMC
April 2021

Luteolin inhibits proliferation, triggers apoptosis and modulates Akt/mTOR and MAP kinase pathways in HeLa cells.

Oncol Lett 2021 Mar 7;21(3):192. Epub 2021 Jan 7.

School of Life Sciences, Manipal Academy of Higher Education, Dubai, United Arab Emirates.

Flavonoids, a subclass of polyphenols, have been shown to be effective against several types of cancer, by decreasing proliferation and inducing apoptosis. Therefore, the aim of the present study was to assess the anti-carcinogenic potential of luteolin on HeLa human cervical cancer cells, through the use of a cell viability assay, DNA fragmentation assay, mitochondrial membrane potential assay, cell cycle analysis using Annexin/PI staining and flow cytometry, gene expression analysis and a protein profiling array. Luteolin treatment exhibited cytotoxicity towards HeLa cells in a dose- and time-dependent manner, and its anti-proliferative properties were confirmed by accumulation of luteolin-treated cells in sub-G phases. Cytotoxicity induced by luteolin treatment resulted in apoptosis, which was mediated through depolarization of the mitochondrial membrane potential and DNA fragmentation. Furthermore, luteolin treatment increased the expression of various proapoptotic genes, including , and and , whereas the expression of anti-apoptotic genes, including and , was decreased. Cell cycle regulatory genes, including and and , were decreased following treatment. Expression of TRAILR2/DR5, TRAILR1/DR4, Fas/TNFRSF6/CD95 and TNFR1/TNFRSF1A, as well as pro-apoptotic proteins, including BAD, BAX and Cytochrome C were consistently increased, and the expression of antiapoptotic proteins, HIF1α, BCL-X, MCL1 and BCL2, were found to be decreased following treatment. Expression of and and was significantly decreased at the transcriptional level. Expression of GSK3b (p-ser9), PRAS 40 (p-Ther246), BAD (p-ser112), PTEN (p-ser380), AKT (p-ser473), ERK2 (p-Y185/Y187), RISK2 (p-ser386), P70S6k (p-Thr421/ser424), PDK1(p-ser241), ERK1 (p-T202/Y204) and MTOR (p-ser2448) was downregulated and expression of P53 (p-ser241) and P27(p-Thr198) was upregulated by luteolin in a dose-dependent manner, indicating its anti-proliferative and apoptosis enabling properties, and this may have been mediated via inhibition of the AKT and the MAPK pathways.
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http://dx.doi.org/10.3892/ol.2021.12452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816384PMC
March 2021

Metformin and Androgen Receptor-Axis-Targeted (ARAT) Agents Induce Two PARP-1-Dependent Cell Death Pathways in Androgen-Sensitive Human Prostate Cancer Cells.

Cancers (Basel) 2021 Feb 5;13(4). Epub 2021 Feb 5.

Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD 21201, USA.

We explored whether the anti-prostate cancer (PC) activity of the androgen receptor-axis-targeted agents (ARATs) abiraterone and enzalutamide is enhanced by metformin. Using complementary biological and molecular approaches, we determined the associated underlying mechanisms in pre-clinical androgen-sensitive PC models. ARATs increased androgren receptors (ARs) in LNCaP and AR/ARv7 (AR variant) in VCaP cells, inhibited cell proliferation in both, and induced poly(ADP-ribose) polymerase-1 (PARP-1) cleavage and death in VCaP but not LNCaP cells. Metformin decreased AR and ARv7 expression and induced cleaved PARP-1-associated death in both cell lines. Metformin with abiraterone or enzalutamide decreased AR and ARv7 expression showed greater inhibition of cell proliferation and greater induction of cell death than single agent treatments. Combination treatments led to increased cleaved PARP-1 and enhanced PARP-1 activity manifested by increases in poly(ADP-ribose) (PAR) and nuclear accumulation of apoptosis inducing factor (AIF). Enhanced annexin V staining occurred in LNCaP cells only with metformin/ARAT combinations, but no caspase 3 recruitment occurred in either cell line. Finally, metformin and metformin/ARAT combinations increased lysosomal permeability resulting in cathepsin G-mediated PARP-1 cleavage and cell death. In conclusion, metformin enhances the efficacy of abiraterone and enzalutamide via two PARP-1-dependent, caspase 3-independent pathways, providing a rationale to evaluate these combinations in castration-sensitive PC.
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http://dx.doi.org/10.3390/cancers13040633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914929PMC
February 2021

Internal Medicine Point of Care Ultrasound in the 21st Century: A 'FoCUS' on the Middle East.

J Saudi Heart Assoc 2020 23;32(4):479-482. Epub 2020 Dec 23.

John A. Buchanan Chair, Division of General Internal Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

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http://dx.doi.org/10.37616/2212-5043.1225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849845PMC
December 2020

Dietary isothiocyanates inhibit cancer progression by modulation of epigenome.

Semin Cancer Biol 2021 Jan 9. Epub 2021 Jan 9.

School of Life Sciences, Manipal Academy of Higher Education, P.O. Box 345050, Dubai, United Arab Emirates. Electronic address:

Cell cycle, growth, survival and metabolism are tightly regulated together and failure in cellular regulation leads to carcinogenesis. Several signaling pathways like the PI3K, WNT, MAPK and NFKb pathway exhibit aberrations in cancer and help achieve hallmark capabilities. Clinical research and in vitro studies have highlighted the role of epigenetic alterations in cancer onset and development. Altered gene expression patterns enabled by changes in DNA methylation, histone modifications and RNA processing have proven roles in cancer hallmark acquisition. The reversible nature of epigenetic processes offers robust therapeutic targets. Dietary bioactive compounds offer a vast compendium of effective therapeutic moieties. Isothiocyanates (ITCs) sourced from cruciferous vegetables demonstrate anti-proliferative, pro-apoptotic, anti-inflammatory, anti-migratory and anti-angiogenic effect against several cancers. ITCs also modulate the redox environment, modulate signaling pathways including PI3K, MAPK, WNT, and NFkB. They also modulate the epigenetic machinery by regulating the expression and activity of DNA methyltransferases, histone modifiers and miRNA. This further enhances their transcriptional modulation of key cellular regulators. In this review, we comprehensively assess the impact of ITCs such as sulforaphane, phenethyl isothiocyanate, benzyl isothiocyanate and allyl isothiocyanate on cancer and document their effect on various molecular targets. Overall, this will facilitate consolidation of the current understanding of the anti-cancer and epigenetic modulatory potential of these compounds and recognize the gaps in literature. Further, we discuss avenues of future research to develop these compounds as potential therapeutic entities.
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http://dx.doi.org/10.1016/j.semcancer.2020.12.021DOI Listing
January 2021

DNA Methylation in Prostate Tumor Tissue Is Associated with Gleason Score.

Genes (Basel) 2020 12 24;12(1). Epub 2020 Dec 24.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA.

Increasing evidence suggests a role of epigenetic mechanisms at chromosome 8q24, an important cancer genetic susceptibility region, in prostate cancer. We investigated whether DNA methylation at 8q24 (six CpG sites from exon 3 to the 3' UTR) in prostate tumor was associated with tumor aggressiveness (based on Gleason score, GS), and we incorporated RNA expression data to investigate the function. We accessed radical prostatectomy tissue for 50 Caucasian and 50 African American prostate cancer patients at the University of Maryland Medical Center, selecting an equal number of GS 6 and GS 7 cases per group. DNA methylation was lower in tumor than paired normal prostate tissue for all six CpG sites (median difference: -14.74 to -0.20 percentage points), and we observed similar results for two nearby sites in The Cancer Genome Atlas ( < 0.0001). We observed significantly lower methylation for more aggressive (GS 7) than less aggressive (GS 6) tumors for three exon 3 sites (for CpG 212 (chr8:128753145), GS 6 median = 89.7%; GS 7 median = 85.8%; -value = 9.4 × 10). DNA methylation was not associated with expression, but was inversely associated with expression after multiple comparison adjustment (-value = 0.04). Findings suggest that prostate tumor exon 3 hypomethylation is associated with increased aggressiveness.
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http://dx.doi.org/10.3390/genes12010012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823928PMC
December 2020

Improving the oxidative stability of fish oil nanoemulsions by co-encapsulation with curcumin and resveratrol.

Colloids Surf B Biointerfaces 2021 Mar 10;199:111481. Epub 2020 Dec 10.

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, China. Electronic address:

Tuna fish oil (TFO), is a rich source of omega-3 fatty acids comprising particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are essential for the human's health enhancement. However, their foremost problems are poor solubility, low bioavailability, and easy oxidization, which limit their wide range of applications in food and pharmaceutical products. The aim of this research is to develop TFO nanoemulsions encapsulating curcumin (CUR) and resveratrol (RES) as co-antioxidants, stabilized with different concentrations of two modified starches including Purity Gum 2000 (PG) and Purity Gum Ultra (PGU). The effect of diverse quantities of modified starches on droplet size, droplet charges, viscosity, and oxidative stability of produced nanoemulsions was assessed at different storage temperatures (4, 25, and 40 °C). Furthermore, to assess the antioxidant activity and capacity of loaded nanoemulsions, DPPH, and ABTS assays were used, respectively. Among various samples, PGU2.5 and PG9 emulsified by PGU and PG2000 had showed the premium results of stability during storage at all temperatures over other formulations. Even at 40 °C, 199.10 μL/mL of PGU2.5 and 258.59 μL/mL of PG9 were required to attain the level of DPPH IC, which were the lowest concentration as compare to other nanoemulsions. Taken together, it was accredited that co-encapsulation of CUR and RES inside the TFO nanoemulsion-based delivery systems can be efficient for the production of functional foods.
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http://dx.doi.org/10.1016/j.colsurfb.2020.111481DOI Listing
March 2021

Multi-organ point-of-care ultrasound for COVID-19 (PoCUS4COVID): international expert consensus.

Crit Care 2020 12 24;24(1):702. Epub 2020 Dec 24.

Ospedale Niguarda C' Grande, Milan, Italy.

COVID-19 has caused great devastation in the past year. Multi-organ point-of-care ultrasound (PoCUS) including lung ultrasound (LUS) and focused cardiac ultrasound (FoCUS) as a clinical adjunct has played a significant role in triaging, diagnosis and medical management of COVID-19 patients. The expert panel from 27 countries and 6 continents with considerable experience of direct application of PoCUS on COVID-19 patients presents evidence-based consensus using GRADE methodology for the quality of evidence and an expedited, modified-Delphi process for the strength of expert consensus. The use of ultrasound is suggested in many clinical situations related to respiratory, cardiovascular and thromboembolic aspects of COVID-19, comparing well with other imaging modalities. The limitations due to insufficient data are highlighted as opportunities for future research.
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http://dx.doi.org/10.1186/s13054-020-03369-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759024PMC
December 2020

In Silico Studies Reveal Antiviral Effects of Traditional Indian Spices on COVID-19.

Curr Pharm Des 2021 ;27(32):3462-3475

Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow 226021 (Uttar Pradesh), India.

Background: The global health emergency due to SARS-CoV-2 causing the COVID-19 pandemic emphasized the scientific community to intensify their research work for its therapeutic solution. In this study, Indian traditional spices owing to various medicinal properties were tested in silico for their inhibitory activity against SARS-CoV-2 proteins. SARS-CoV-2 spike proteins (SP) and main proteases (M) play a significant role in infection development were considered as potential drug targets.

Methods: A total of 75 phytochemicals present in traditional Indian spices retrieved from the published literature and Dr. Duke's Phytochemical and Ethnobotanical Database, were docked with M (PDB IDs: 6YNQ), and the SP (PDB IDs: 6LXT and 6YOR).

Results: Through the screening process, 75 retrieved phytochemicals were docked with spike protein (PDB IDs: 6LXT and 6YOR) and main protease (PDB ID: 6YNQ) of SARS-CoV-2. Among them, myricetin, a flavonoid (rank score: 6LXT: -11.72383; 6YOR: -9.87943; 6YNQ: -11.68164) from Allium sativum L and Isovitexin, an example of flavone (rank score: 6LXT: -12.14922; 6YOR: -10.19443; 6YNQ: -12.60603) from Pimpinella anisumL were the most potent ligands against SP and M of SARS-CoV-2. Whereas, Astragalin from Crocus sativus L.; Rutin from Illicium verum, Oxyguttiferone from Garcinia cambogia; Scopolin from Apium graveolens L, Luteolin from Salvia officinalis, Emodin, Aloe-emodin from Cinnamomum zeylanicium and Apigenin from Allium sativum L showed better inhibition against M than SP of SARS-CoV-2. The amino acid residues like SER, LYS, ASP and TYR were found playing important role in protein-ligand interactions via hydrogen bonding and Vander Waals forces.

Conclusion: Optimal use of traditional spices in our daily meals may help fight against COVID-19. This study also paves the path for herbal drug formulation against SARS-CoV-2 after wet lab validation.
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http://dx.doi.org/10.2174/1381612826666201223095548DOI Listing
October 2021

Bedside noninvasive monitoring of mechanically ventilated patients.

Curr Opin Crit Care 2021 02;27(1):66-75

Department of Adult Critical Care, Guy's and St Thomas' NHS Foundation Trust, King's Health Partners, and Division of Centre of Human Applied Physiological Sciences, King's College London, London, UK.

Purpose Of Review: Among noninvasive lung imaging techniques that can be employed at the bedside electrical impedance tomography (EIT) and lung ultrasound (LUS) can provide dynamic, repeatable data on the distribution regional lung ventilation and response to therapeutic manoeuvres.In this review, we will provide an overview on the rationale, basic functioning and most common applications of EIT and Point of Care Ultrasound (PoCUS, mainly but not limited to LUS) in the management of mechanically ventilated patients.

Recent Findings: The use of EIT in clinical practice is supported by several studies demonstrating good correlation between impedance tomography data and other validated methods of assessing lung aeration during mechanical ventilation. Similarly, LUS also correlates with chest computed tomography in assessing lung aeration, its changes and several pathological conditions, with superiority over other techniques. Other PoCUS applications have shown to effectively complement the LUS ultrasound assessment of the mechanically ventilated patient.

Summary: Bedside techniques - such as EIT and PoCUS - are becoming standards of the care for mechanically ventilated patients to monitor the changes in lung aeration, ventilation and perfusion in response to treatment and to assess weaning from mechanical ventilation.
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http://dx.doi.org/10.1097/MCC.0000000000000789DOI Listing
February 2021

Silybin B and Cianidanol Inhibit M and Spike Protein of SARS-CoV-2: Evidence from in silico Molecular Docking Studies.

Curr Pharm Des 2021 ;27(32):3476-3489

Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow- 226021, Uttar Pradesh, India.

Background: The main proteases (Mpro) and Spike Proteins (SP) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) play a major role in viral infection development by producing several non-structural proteins (nsPs) and penetrating the host cells, respectively. In this study, the potential of in silico molecular docking-based drug repositioning approach was exploited for identifying the inhibitors of M and SP of SARS-CoV-2.

Methods: A total of 196 compounds, including various US-FDA-approved drugs, vitamins, and their analogs, were docked with M (PDB IDs: 6YB7 and 6Y84), and the top six ligands were further tested for ADME properties, followed by docking with SP (PDB IDs: 6LXT and 6W41).

Results: Out of 196 compounds, binding energy (DE) of Silybin B (6YB7: DE: -11.20 kcal/mol; 6Y84: DE: - 10.18 kcal/mol; 6LXT: DE: -10.47 kcal/mol; 6W41: DE: -10.96 kcal/mol) and Cianidanol (6YB7: DE: -8.85 kcal/mol; 6LXT: DE: -9.36 kcal/mol; 6Y84: DE: -10.02 kcal/mol; 6W41: DE: -9.52 kcal/mol) demonstrated better binding and ADME properties compared with the currently endeavored drugs like Hydroxychloroquine and Lopinavir. Additionally, Elliptinone, Diospyirin, SCHEMBL94263, and Fiboflavin have shown encouraging results. Fiboflavin, an immunity booster, was found to inhibit both the M and spike protein of SARSCoV- 2. It was observed that amino acid residues MET6, ALA7, PHE8, PRO9, ASP295, GLY302, VAL303, and THR304 play significant roles in protein-ligand interactions through hydrogen bonds and Vander Waals forces.

Conclusion: Silybin B and Cianidanol showed excellent binding and ADME properties compared with the currently endeavored drugs and can be exploited as therapeutic options against SARS-CoV-2 infection after experimental validation and clinical trials.
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http://dx.doi.org/10.2174/1381612826666201210122726DOI Listing
October 2021

Canadian Internal Medicine Ultrasound (CIMUS) Expert Consensus Statement on the Use of Lung Ultrasound for the Assessment of Medical Inpatients With Known or Suspected Coronavirus Disease 2019.

J Ultrasound Med 2021 Sep 4;40(9):1879-1892. Epub 2020 Dec 4.

Division of Emergency Ultrasound, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Objectives: To develop a consensus statement on the use of lung ultrasound (LUS) in the assessment of symptomatic general medical inpatients with known or suspected coronavirus disease 2019 (COVID-19).

Methods: Our LUS expert panel consisted of 14 multidisciplinary international experts. Experts voted in 3 rounds on the strength of 26 recommendations as "strong," "weak," or "do not recommend." For recommendations that reached consensus for do not recommend, a fourth round was conducted to determine the strength of those recommendations, with 2 additional recommendations considered.

Results: Of the 26 recommendations, experts reached consensus on 6 in the first round, 13 in the second, and 7 in the third. Four recommendations were removed because of redundancy. In the fourth round, experts considered 4 recommendations that reached consensus for do not recommend and 2 additional scenarios; consensus was reached for 4 of these. Our final recommendations consist of 24 consensus statements; for 2 of these, the strength of the recommendations did not reach consensus.

Conclusions: In symptomatic medical inpatients with known or suspected COVID-19, we recommend the use of LUS to: (1) support the diagnosis of pneumonitis but not diagnose COVID-19, (2) rule out concerning ultrasound features, (3) monitor patients with a change in the clinical status, and (4) avoid unnecessary additional imaging for patients whose pretest probability of an alternative or superimposed diagnosis is low. We do not recommend the use of LUS to guide admission and discharge decisions. We do not recommend routine serial LUS in patients without a change in their clinical condition.
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http://dx.doi.org/10.1002/jum.15571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451849PMC
September 2021

Point-of-Care Ultrasound Training: An Assessment of Interns' Needs and Barriers to Training.

Cureus 2020 Oct 28;12(10):e11209. Epub 2020 Oct 28.

Anesthesiology/Cardiac and Critical Care, King Abdulaziz Medical City, Riyadh, SAU.

Background and objective The use of point-of-care ultrasound (POCUS) is generally on the rise worldwide. However, as the epidemiology of diseases and the approach to their management vary internationally, POCUS may not be universally applicable. The resources available for medical education are generally limited. Thus, when considering the development of a training program during the internship year, we sought to determine interns' perceptions of the applicability of POCUS to clinical practice, the current skill gaps, and barriers to training. Methods  A validated questionnaire was distributed to the interns of the College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh to determine their proficiency in POCUS, and their opinions on its applicability on a 5-point Likert scale. Each skill gap was calculated by subtracting self-reported proficiency in POCUS from its perceived applicability. Results Of the 300 total interns (male: 200, female: 100), 229 participated [response rate: 76%; male: 136 (68%), female: 93 (93%)]. The use of POCUS to detect abdominal free fluid was perceived to be the most applicable use (mean: 3.9 ±1.1); scanning for consolidation was the least applicable (mean: 3.0 ±1.2). Knowledge and proficiency among the sample were generally poor. The skill gap was greatest for the assessment of inferior vena cava collapsibility (mean: 1.4 ±1.3) and least for the identification of pneumothorax (mean: 0.5 ±1.5). Although three-quarters of the participants (170) agreed that POCUS was an essential skill, 36 (16%) stated that they had no interest in it, and nearly half (101) believed that they did not have time to learn POCUS. Conclusions  While POCUS is applicable to medical interns in Saudi Arabia, significant skill gaps exist. However, our sample's perception of the applicability of POCUS was less favorable than that of internal medicine (IM) residents in Canada. Thus, initiating POCUS training during the internship year may yield suboptimal results. Interns must prioritize medical licensing examinations and applications for residency training. Indeed, many interns believe that they do not have enough time to learn POCUS. Thus, prioritizing the training of residents in POCUS may be a more effective use of the finite resources available for medical education.
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http://dx.doi.org/10.7759/cureus.11209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704159PMC
October 2020

Feasibility of using a handheld ultrasound device to detect and characterize shunt and deep vein thrombosis in patients with COVID-19: an observational study.

Ultrasound J 2020 Nov 30;12(1):49. Epub 2020 Nov 30.

Department of Medicine, King Abdulaziz Medical City, King Abdulaziz International Medical Research Center, Ministry of National Guard - Health Affairs, Riyadh, Saudi Arabia.

Background: Coronavirus disease 2019 (COVID-19) causes an atypical acute respiratory distress syndrome associated with thromboembolism and high shunt fraction. Shunt may be intrapulmonary, or extrapulmonary. Handheld devices are increasingly being used for point-of-care ultrasound, but their use to characterize shunt has not been reported.

Objectives: Determine the feasibility of using handheld ultrasound to detect and characterize anatomical substrates of hypoxia and deep vein thrombosis (DVT) in patients with COVID-19 suspected to have severe shunt.

Methods: A handheld ultrasound device (iQ, Butterfly, USA) was used to perform lung ultrasound, vascular assessment for DVT, and limited transthoracic echocardiography (TTE) with color Doppler and saline microbubble contrast in patients with COVID-19 suspected to have severe shunt. Images were reassessed by an independent reviewer.

Results: After screening 40 patients, six patients who fulfilled the inclusion criteria were identified. Two were excluded because palliation had been initiated. So, four patients were studied. Interpretable images were obtained in all cases. Interobserver agreement was good. All patients had abnormal lung ultrasound (lung ultrasound score range 17-22). Identified lung pathology included interstitial syndrome with light beams and small peripheral consolidation (4), lobar consolidation (1), and pleural effusion (1). Abnormal echocardiographic findings included interatrial shunt (2), intrapulmonary shunt (1), and dilated right ventricle with tricuspid valve regurgitation (1). Significant DVT was not detected.

Conclusion: Use of handheld ultrasound to perform combined lung ultrasound, DVT ultrasound, and limited TTE with color Doppler and saline microbubble contrast is feasible, and may be able to characterize shunt in critically hypoxic patients. Serial studies could be used to monitor changes in shunt. Further studies are required to determine whether this can guide treatment to improve the outcomes of patients with refractory hypoxia.
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http://dx.doi.org/10.1186/s13089-020-00197-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702202PMC
November 2020

High Prevalence of Gene among Extended-Spectrum β-Lactamase-Producing Isolates Causing Extraintestinal Infections in Bangladesh.

Antibiotics (Basel) 2020 Nov 11;9(11). Epub 2020 Nov 11.

Laboratory Sciences and Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka-1212, Bangladesh.

The emergence of multidrug-resistant (MDR) () clonal lineages with high virulence potential is alarming. Lack of sufficient data on molecular epidemiology of such pathogens from countries with high infection burden, such as Bangladesh, hinders management and infection control measures. In this study, we assessed the population structure, virulence potential and antimicrobial susceptibility of clinical isolates from Dhaka, Bangladesh. A high prevalence of MDR (69%) and extended-spectrum β-lactamase production (ESBL) (51%) was found. Most isolates were susceptible to amikacin (95%), meropenem (94%) and nitrofurantoin (89%) antibiotics. A high prevalence of ST131 (22%) and ST95 (9%) followed by ST69 (4%) and ST73 (3%) was observed. Phylogroups B2 (46%), B1 (16%), D (10%) and F (9%) were prominent. (52%) and (5%) were the most prevalent ESBL and carbapenem resistance genes, respectively. Moreover, the predominant pathotype identified was extraintestinal pathogenic (ExPEC) (41%) followed by enteric pathogens (11%). In conclusion, our results suggest the transmission of clonal groups amidst diverse population that are associated with high virulence potential and MDR phenotype. This is of high concern and mandates more efforts towards molecular surveillance of antimicrobial resistance (AMR) in clinically significant pathogens.
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http://dx.doi.org/10.3390/antibiotics9110796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696227PMC
November 2020

Epigallocatechin gallate inhibits HeLa cells by modulation of epigenetics and signaling pathways.

3 Biotech 2020 Nov 23;10(11):484. Epub 2020 Oct 23.

School of Life Sciences, Manipal Academy of Higher Education, PO Box 345050, Dubai, United Arab Emirates.

This study examines the effect of epigallocatechin gallate (EGCG) on signaling pathways, epigenetic modulators and tumour suppressor genes in cervical cancer cells, HeLa. qRT-PCR, ELISA-based enzymatic assays and in silico studies were used to catalogue the modulation of these genes by EGCG treatment. qRT-PCR showed transcriptional modulation of several epigenetic modifiers including DNA methyltransferases and histone modifiers (DNMT1, DNMT3B, DNMT3A, AURKA, AURKC, AURKB, KDM4A, KDM5C, PRMT7, PRMT6, UBE2B, HDAC5, HDAC6, HDAC7 and HDAC11. Furthermore, ELISA-based assays showed that EGCG lowered the activity of DNA methyltransferases, histone deacetylases and histone methyltransferases (H3K9). Molecular docking results suggests that EGCG may competitively inhibit some epigenetic enzymes (DNMT1, DNMT3A, HDAC2, HDAC3, HDAC4, HDAC7 and EZH2). A functional outcome of these epigenetic alterations could be inferred from the reversal of promoter hypermethylation of tumour suppressor genes by quantitative methylation array and transcriptional re-expression of tumour suppressor genes including and by qRT-PCR. Downregulation of key signaling moieties of PI3K, Wnt and MAPK pathways, cell cycle regulators, metastasis regulators and pro-inflammatory moieties including and was also observed. In silico protein-protein interaction network analysis followed by KEGG analysis discerned the active participation of gene sets towards cancer pathways. This study comprehensively explains EGCG's anti-cancer mechanism via the synchronized transcriptional alteration of several molecular targets across different signaling pathways and reversal of tumour suppressor gene silencing through modulation of epigenetic enzymes.
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http://dx.doi.org/10.1007/s13205-020-02473-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584697PMC
November 2020

Draft Genome Sequence of Chromobacterium violaceum RDN09, Isolated from a Patient with a Wound Infection in Bangladesh.

Microbiol Resour Announc 2020 Oct 15;9(42). Epub 2020 Oct 15.

Laboratory Sciences and Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh

is an emerging environmental opportunistic pathogen that causes life-threatening infections in humans. Here, we describe the draft genome sequence of RDN09, isolated from the infected wound of an adult male patient in Bangladesh. The genome assembly consists of 4,736,739 bp spread across 84 contigs.
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http://dx.doi.org/10.1128/MRA.00957-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561691PMC
October 2020

Bone health effects of androgen-deprivation therapy and androgen receptor inhibitors in patients with nonmetastatic castration-resistant prostate cancer.

Prostate Cancer Prostatic Dis 2021 06 7;24(2):290-300. Epub 2020 Oct 7.

Indiana University School of Medicine, Indianapolis, IN, USA.

Background: Osteoporosis is a skeletal disorder characterized by compromised bone strength, resulting in increased fracture risk. Patients with prostate cancer may have multiple risk factors contributing to bone fragility: advanced age, hypogonadism, and long-term use of androgen-deprivation therapy. Despite absence of metastatic disease, patients with nonmetastatic castrate-resistant prostate cancer receiving newer androgen receptor inhibitors can experience decreased bone mineral density. A systematic approach to bone health care has been hampered by a simplistic view that does not account for heterogeneity among prostate cancer patients or treatments they receive. This review aims to raise awareness in oncology and urology communities regarding the complexity of bone health, and to provide a framework for management strategies for patients with nonmetastatic castrate-resistant prostate cancer receiving androgen receptor inhibitor treatment.

Methods: We searched peer-reviewed literature on the PubMed database using key words "androgen-deprivation therapy," "androgen receptor inhibitors," "bone," "bone complications," and "nonmetastatic prostate cancer" from 2000 to present.

Results: We discuss how androgen inhibition affects bone health in patients with nonmetastatic castrate-resistant prostate cancer. We present data from phase 3 trials on the three approved androgen receptor inhibitors with regard to effects on bone. Finally, we present management strategies for maintenance of bone health.

Conclusions: In patients with nonmetastatic castrate-resistant prostate cancer, aging, and antiandrogen therapy contribute to bone fragility. Newer androgen receptor inhibitors were associated with falls or fractures in a small subset of patients. Management guidelines include regular assessment of bone density, nutritional guidance, and use of antiresorptive bone health agents when warranted.
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http://dx.doi.org/10.1038/s41391-020-00296-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134041PMC
June 2021
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