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HERPUD1, a Member of the Endoplasmic Reticulum Protein Quality Control Mechanism, may be a Good Target for Suppressing Tumorigenesis in Breast Cancer Cells

Turk J Pharm Sci. 2023 Jul 7;20(3):157-164. doi: 10.4274/tjps.galenos.2022.71643.

ABSTRACT

OBJECTIVES: Breast cancer is the most frequently diagnosed cancer type and the second leading cause of cancer-related death in women. Recent studies have highlighted the importance of the endoplasmic reticulum (ER) protein quality control mechanism for the survival of many cancers. It has also been recommended as a good target for the treatment of many cancer types. Homocysteine inducible ER protein with ubiquitin-like domain 1 (HERPUD1) functions as one of the main components of ER-associated degradation, which is an ER-resident protein quality mechanism. Today, the association of HERPUD1 with breast carcinogenesis is still not fully understood. Herein, we evaluated the possibility of HERPUD1 as a potential therapeutic target for breast cancer.

MATERIALS AND METHODS: The effects of HERPUD1 silencing on epithelial-mesenchymal transition (EMT), angiogenesis, and cell cycle proteins were analyzed by immunoblotting studies. To test the role of HERPUD1 on tumorigenic features, WST-1-based cell proliferation assay, wound-healing assay, 2D colony formation assay, and Boyden-Chamber invasion assay were performed in human breast cancer cell line MCF-7. The statistical significance of the differences between the groups was determined by Student’s t-test.

RESULTS: Our results displayed that suppressing HERPUD1 expression reduced the cell cycle-related protein levels, including cyclin A2, cyclin B1, and cyclin E1 in MCF-7 cells. Also, silencing of HERPUD1 remarkably decreased expression levels of EMT-related N-cadherin and angiogenesis marker vascular endothelial growth factor A. Moreover, we determined that cell proliferation, migration, invasion, and colony formation of MCF-7 cells were significantly limited by silencing of HERPUD1.

CONCLUSION: Present data suggest that HERPUD1 may be an effective target for biotechnological and pharmacological strategies to be developed to treat breast cancer.

PMID:37417198 | DOI:10.4274/tjps.galenos.2022.71643

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Association between smoking and colorectal cancer in Eastern Mediterranean Regional Office (EMRO): A systematic review and meta-analysis

Saudi J Gastroenterol. 2023 Jul 4. doi: 10.4103/sjg.sjg_163_23. Online ahead of print.

ABSTRACT

BACKGROUND: Smoking poses a significant risk for colorectal cancer (CRC), considered the third leading reason for cancer-related deaths worldwide. However, there has been limited research on the relationship between smoking and CRC in the Eastern Mediterranean Regional Office (EMRO). Therefore, a meta-analysis was conducted to combine available data and gain a comprehensive understanding of the relationship between smoking and CRC in EMRO.

METHODS: Two independent researchers searched PubMed, Scopus, and Web of Science until December 2022. The included studies were checked for risk of bias administering the Newcastle-Ottawa scale. Heterogeneity was evaluated using I2 statistics and the Cochrane test. Publication bias was determined through funnel plot analysis and Egger’s regression test. Additionally, a meta-regression analysis explored the impact of a country’s Human Development Index (HDI) on the relationship between smoking and CRC.

RESULTS: The final analysis included 26 studies, revealing a significant association between smoking and CRC (OR = 1.40; 95% CI: 1.11 – 1.78; P = 0.004). Moreover, smoking had a more pronounced adverse effect on CRC in countries with higher HDIs compared to those with lower HDIs (OR = 1.30; 95% CI: 0.99 – 1.71; P = 0.054).

CONCLUSIONS: Our findings underscore the importance of implementing smoking cessation programs and policies in EMRO countries, as they demonstrate a positive relationship between smoking and the risk of CRC. Furthermore, the results suggest that a country’s level of human development may influence the association between smoking and CRC. Further research is needed to investigate this potential connection and develop targeted public health interventions.

PMID:37417191 | DOI:10.4103/sjg.sjg_163_23

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Clinical Profile, Outcomes, and Complications in Neonates Undergoing Peritoneal Dialysis in a Tertiary Neonatal Care Unit – An Observational Study

Saudi J Kidney Dis Transpl. 2022 Mar-Apr;33(2):337-342. doi: 10.4103/1319-2442.379034.

ABSTRACT

Peritoneal dialysis (PD) is the most common form of renal replacement therapy in neonates and there is a lot of heterogeneity in patient selection and outcomes across the various units. This study aimed to assess the indications, complications, and outcomes in terms of survival of PD. This is a retrospective study of 23 neonates who underwent acute PD at a tertiary care neonatal unit between August 2016 and July 2021. A cross-sectional poll was also conducted among the doctors who have been in the unit for the past 10 years regarding their experience in PD. The baseline, clinical, biochemical parameters, outcomes, and complications were analyzed. All statistical analyses were performed using the IBM SPSS Statistics version 23.0 software. The mean (±standard deviation) gestational age and birth weights of neonates were 32.6 ± 4 weeks and 1743 ± 922 g, respectively. Six (26%) babies had extremely low birth weight, five (22%) very low birth weight (VLBW), and seven (30%) low birth weight. The indications were acute kidney injury [17/23 (74%)], fluid overload [3/23 (17%)], suspected inborn errors of metabolism [2/23 (9%)] and hypernatremia [1/23 (4%)]. A pigtail catheter (74%) was used in most of them. Catheter block was noticed in four babies and peritonitis in two neonates. We did not encounter any complications during the procedure, and PD appears to be practicable across all gestational ages and birth weights.

PMID:37417188 | DOI:10.4103/1319-2442.379034

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Left Ventricular Mass and Functions in Egyptian Children with Chronic Kidney Disease in Comparison to Normal Subjects

Saudi J Kidney Dis Transpl. 2022 Mar-Apr;33(2):296-306. doi: 10.4103/1319-2442.379028.

ABSTRACT

Left ventricular hypertrophy (LVH) and cardiac fibrosis are common accompaniments of chronic kidney disease (CKD). They can be rather easily assessed by conventional cardiac imaging modalities, most practically by M-mode or two-dimensional (2D) echocardiography, with adequate recognition of pitfalls. This study uncovers the impact of impaired renal function on left ventricular mass (LVM) and LVM index (LVMI) in children with CKD on regular hemodialysis (HD) attending the Zagazig University Hospital for Children. A total of 80 Egyptian children, out of which 40 subjects having a mean age of 11.2 ± 3.12 years were cases with CKD in stage 5 on regular HD and the other 40 healthy subjects as controls, with a mean age of 12.2 ± 2.54 years, were included in the study and assessed for LVH and LVMI by 2D echocardiography. HD children had a significantly higher mean LVMI (102.3 ± 19.1 vs. 49.6 ± 4.11 g/m2, P <0.001) than controls. Relative wall thickness was significantly higher in the patients with CKD patients on HD compared with controls (P <0.001) with a mean value of 0.46 indicating concentric LVH in renal patients. Comparing mitral inflow velocities between both the groups revealed that the patient group had a significant decrease in mitral E-wave velocity (0.88 ± 0.2 vs. 1.1 ± 0.1 m/sec, P <0.001) and E/A velocity ratio (1.3 ± 0.3 vs. 1.7 ± 0.3, P <0.001) in comparison with the control group, but there was no statistically significant difference in A-wave velocity. This indicates early diastolic dysfunction in CKD patients. LV mass changes in CKD children were strongly related to hypocalcemia and Vitamin D deficiency. Children with CKD are prone to the development of cardiac diastolic dysfunction and LVH, so early and regular echocardiographic studies of all children with CKD are recommended to detect early cardiac changes and institute interventions.

PMID:37417182 | DOI:10.4103/1319-2442.379028

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Anti-phospholipase A2 Receptor Antibody in Differentiation and Prognostication of Membranous Nephropathy

Saudi J Kidney Dis Transpl. 2022 Mar-Apr;33(2):280-287. doi: 10.4103/1319-2442.379026.

ABSTRACT

Anti-M-type phospholipase A2 receptor (anti-PLA2R) antibody is believed to be associated with primary membranous nephropathy (pMN) and absent in secondary MN (sMN). There are few data regarding utility of anti-PLA2R antibody as a prognosticator. Our study aimed to compare the incidence of positive serum anti-PLA2R antibody titer in pMN versus sMN and correlation with clinical outcome. From August 2015 to July 2019, patients with biopsy-proven MN were evaluated for serum anti-PLA2R antibody titers by the enzyme-linked immunosorbent assay. The subset of cases was repeated to monitor the clinical response in terms of 24 h proteinuria. A total of 169 patients, 65 pMN and 104 sMN were studied. Anti-PLA2R antibody was found in 41 (63.08%) pMN with mean titer, 232.62 RU/mL, and 40 (38.46%) sMN with mean titer 253.59 RU/mL. Out of positive antiPLA2R antibody titer in pMN cases, 15 were retested twice to 5 times with mean titers of 78.95, 36.27, 13.9, and 15.45 RU/mL, respectively. Out of positive anti-PLA2R antibody in sMN cases, 11 were retested twice to five times with mean titers of 104.42, 122.49, 12.33, and 17.2 RU/mL, respectively. All patients with decreasing anti-PLA2R antibody titer in both groups had clinical remission, with a decrease in mean 24 h proteinuria from 7.11 g to 3.36 g in pMN and 5.97 g to 3.41 g in sMN. Ten pMN and 11 sMN patients without remission showed persistent positive anti- PLA2R antibody titer. Anti-PLA2R antibody titer may be elevated in pMN/sMN. It can also be used as a noninvasive prognostic marker for MN.

PMID:37417180 | DOI:10.4103/1319-2442.379026

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Impact of Adipokines in Brachial Artery Flow-mediated Dilatation in Lupus Nephritis

Saudi J Kidney Dis Transpl. 2022 Mar-Apr;33(2):272-279. doi: 10.4103/1319-2442.379025.

ABSTRACT

Endothelial dysfunction is evident in systemic lupus erythematosus (SLE). Pro-inflammatory adipokines are involved in endothelial derangement and premature atherosclerosis, particularly in lupus nephritis (LN). This study aimed to investigate the impact of LN on endothelial function by estimating the serum levels of adiponectin, leptin, visfatin, and homeostatic model assessment-insulin resistance (HOMA-IR) and calculating the flow-mediated dilatation (FMD) of the brachial artery. This is a case-control study in which 190 systemic lupus patients who were fulfilling the American College of Rheumatology revised classification were enrolled. The patients were divided into 100 LN patients and 90 lupus non-nephritis patients. Demographic data, clinical parameters, and SLE activity were reported. Serum adiponectin, leptin, visfatin, and HOMA-IR were measured. The endothelial dysfunction was assessed by calculating the FMD of the brachial artery. The mean age of participants was 25.62 ± 5.81 years. Elevated levels of adiponectin, leptin, visfatin, and HOMA-IR were observed in LN cases (12.2 ± 0.3, 20.1 ± 0.5, 16.8 ± 0.1, and 12.0 ± 3.8, respectively) compared to non-nephritis cases (12.2 ± 0.3, 8.5 ± 0.5, 16.8 ± 0.5, and 9.0 ± 3.8, respectively) with a more reduced FMD percentage in LN cases with a statistical significance. Brachial artery FMD is negatively correlated with lipid profile, adipokines, and HOMA. Visfatin has better sensitivity (82.1%) and specificity (81%) with the area under a curve of 0.893, compared to other biomarkers. LN patients are characterized by impaired endothelial function. Elevated serum adiponectin, visfatin, and HOMA-IR were significantly correlated with poor FMD of the brachial artery. Visfatin has a better performance in detecting atherosclerosis.

PMID:37417179 | DOI:10.4103/1319-2442.379025

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The Effect of Higher and Lower Protein Intakes on Nitrogen Balance in Renal Transplant Recipients with Underlying Graft Dysfunction

Saudi J Kidney Dis Transpl. 2022 Mar-Apr;33(2):236-244. doi: 10.4103/1319-2442.379021.

ABSTRACT

It is essential to determine the optimum protein intake in renal transplant recipients on steroids with renal dysfunction to maintain a neutral nitrogen balance. Our aim was to study the effect of higher (1.2 g/kg/day) and lower (0.8 g/kg/day) protein intakes on nitrogen balance, body composition, glomerular filtration rate (GFR), and proteinuria in renal transplant recipients with low estimated GFR (eGFR) (15-44 mL/min/1.73 m2). This prospective, open-labeled, randomized, cross-over, interventional study enrolled patients who were ≥4 months posttransplant with eGFR between 15 and 44 mL/min/1.73 m2. Subjects were randomized to either Group 1 [Diet: proteins (1.2 g/kg/day), 35 kcal/kg/day] or Group 2 [Diet: proteins (0.8 g/kg/day) and 35 kcal/kg/day] for one month. Subjects crossed over to the other diet for 2nd month. Body composition analysis, serum creatinine, blood urea nitrogen, serum protein, serum albumin, 24-h proteinuria, GFR measurement (24 h creatinine clearance), three-day diet recall and nitrogen balance estimation were performed at baseline and at the end of the first and 2nd month. Statistical analysis was performed using IBM SPSS Statistics version 21. Thirty-two of 35 patients completed the study. Three-day diet recall showed that daily protein and energy consumption was 1.2 g/kg and 36.47 kcal/kg with higher and 0.94 g/kg and 31.94 kcal/kg with lower protein diets, respectively. Nitrogen balance was +3.61 g/day (P = 0.0002) with higher and +1.66 g/day with lower protein diets. A significant increase was noted in muscle mass (P = 0.0317), blood urea nitrogen (P = 0.0118), GFR (P = 0.0114), and proteinuria (P = 0.010) with a higher protein diet. Renal transplant recipients remained in positive nitrogen balance with both diets. Muscle mass and proteinuria increased significantly with a higher protein diet.

PMID:37417175 | DOI:10.4103/1319-2442.379021

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Impact of COVID-19 lockdown during 2020 on the occurrence of vector-borne diseases in India

J Vector Borne Dis. 2023 Apr-Jun;60(2):207-210. doi: 10.4103/0972-9062.364762.

ABSTRACT

BACKGROUND & OBJECTIVES: India imposed one of the world’s largest nationwide lockdown in the aftermath of COVID-19 pandemic in March 2020 which was partly extended up to December. Some of the impacts of the COVID-19 lockdown on the economy, research, travel, education, and sports were readily apparent; the same was less obvious in the occurrence of vector-borne diseases (VBDs). The objective of this study was to statistically determine the impact of the COVID-19 lockdown on the occurrence of VBDs in India.

METHODS: The reported incidence of VBDs such as malaria, dengue, Chikungunya, Japanese encephalitis, and kala-azar in India during the years 2015-2019 was analyzed by fitting Poisson and negative binomial (NB) models for each VBDs separately. The number of cases reported was compared with the number of cases predicted for each year from 2015 to 2020 for all the VBDs under study to infer whether or not the lockdown had any impact on their prevalence in India.

RESULTS: The percentage of the actual case was lower by 46, 75, 49, 72, and 38 respectively for malaria, dengue, Chikungunya, Japanese encephalitis, and kala-azar when comparing the lockdown period and the year before lockdown (2020 vs. 2019). The number of cases predicted for the year 2020 based on the trend of the five preceding years (2015-2019) also showed a great variation between actual and predicted cases. The differences in cases were considered as the cases missed in 2020 were largely due to the lockdown.

INTERPRETATION & CONCLUSION: The analysis showed that the lockdown had a considerable impact on the occurrence of VBDs.

PMID:37417171 | DOI:10.4103/0972-9062.364762

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Non-pathologic components are associated with reduced visual acuity in myopes after spectacle correction

Indian J Ophthalmol. 2023 Jul;71(7):2862-2865. doi: 10.4103/IJO.IJO_2_23.

ABSTRACT

PURPOSE: To find the association between reduced best-corrected visual acuity and non-pathologic components after optical correction in individuals with low to high myopia.

METHODS: Myopic children under 16 years of age were reviewed using electronic medical records and the following data were extracted and recorded: participant’s age, gender, uncorrected visual acuity (UCVA), manifest refraction, and best corrected visual acuity (BCVA). Spherical equivalent and cylinder were classified into low, moderate, and high categories based on the magnitude range. Similarly, astigmatism was defined into with-the-rule, against-the-rule, and oblique based on the location of the steepest meridian. Reduced BCVA was defined when the decimal visual acuity was less than 0.66 (equivalent to Snellen’s acuity of 6/9 or 20/30). Logistic regression was performed to test the factors associated with reduced visual acuity after optical correction in the absence of myopic pathologic changes. Statistical significance was considered if P < 0.05.

RESULTS: Overall 44.9% (N = 242/538) of myopes had reduced best-corrected visual acuity (BCVA) and none of the patients had pathologic myopic lesions. Using logistic regression, we found that high spherical refraction (OR 27.98, 95% CI 14.43-54.25, P < 0.001) and moderate spherical refraction (OR 5.52, 95% CI 2.56-11.91, P < 0.001) were significantly associated with reduced best corrected visual acuity despite any pathological lesions. Additionally, oblique and ATR astigmatism were associated with reduced visual acuity in myopic children with (OR 2.05, 95% CI 0.77-5.42) and (OR 1.59, 95% CI 0.82-3.08).

CONCLUSION: Higher magnitude of refractive error components causes reduced visual acuity in the absence of pathologic changes.

PMID:37417135 | DOI:10.4103/IJO.IJO_2_23

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A cross-sectional study of the impact of the COVID-19 pandemic on an ophthalmology consult service in four Michigan community hospitals

Indian J Ophthalmol. 2023 Jul;71(7):2856-2861. doi: 10.4103/IJO.IJO_82_23.

ABSTRACT

PURPOSE: During the coronavirus disease 2019 (COVID-19) pandemic, private practice, inpatient consult services, and academic residency programs in ophthalmology saw a decrease in patient encounters. This study elucidates how community hospital ophthalmology consult (OC) services were affected during the pandemic. We aim to determine whether there was a change in resident OC volume in a community-based ophthalmology program consult service during the COVID-19 pandemic. Secondary objectives included analyzing the change in the types of diagnoses and the number of patients seen for diabetic retinopathy over the same time.

METHODS: A retrospective cross-sectional study was conducted reviewing the electronic health record (EHR) charts from OCs for the period 2017-2021. Records were categorized by referral source and the nature of OCs (trauma, acute, or chronic); OCs were further grouped by year and weak of referral. An intermonth analysis of weekly OC counts in each category was performed for the average number of consults in February-April 2017-2019 and for February-April 2020. A one-tailed t-test was performed. All t-tests assumed equal variances.

RESULTS: Weekly OCs in 2020 revealed no statistically significant differences in overall cases or in acute or chronic cases when the volume before the COVID-19 pandemic was compared to the volume after the onset of the pandemic. However, a statistically significant increase in the average weekly trauma cases was noted when 2020 (an average of 2.7 cases per week) was compared to the weekly average for the same weeks of years 2017- 2019 (0.4; P = 0.016). This statistically significant increase in trauma in 2020 disappeared when comparing weeks 11-17 in 2020 (2.2 cases per week) and the average of 2017-2019 (1.1).

CONCLUSION: This report outlines no significant change in OCs before and after the onset of the pandemic compared to three previous years. There was, however, an increase in trauma consults during the pandemic and an increase in the number (though not the proportion) of diabetic retinopathy (DR+) patients seen by residents. This report uniquely describes no significant changes in the resident volume of patients seen during the COVID-19 global pandemic.

PMID:37417134 | DOI:10.4103/IJO.IJO_82_23