The Nexus Between COVID-19 Factors and Air Pollution.

Background and Objective: There have been significant effects of the current coronavirus-19 (COVID-19) infection outbreak on many facets of everyday life, particularly the environment. Despite the fact that a number of studies have already been published on the topic, an analysis of those studies' findings on COVID-19's effects on environmental pollution is still lacking. The goal of the research is to look into greenhouse gas emissions and air pollution in Bangladesh when COVID-19 is under rigorous lockdown. The specific drivers of the asymmetric relationship between air pollution and COVID-19 are being investigated. Methods: The nonlinear relationship between carbon dioxide ( C O 2 ) emissions, fine particulate matter ( P M 2 . 5 ) , and COVID-19, as well as its precise components, are also being investigated. To examine the asymmetric link between COVID-19 factors on C O 2 emissions and P M 2 . 5 , we employed the nonlinear autoregressive distributed lag (NARDL) model. Daily positive cases and daily confirmed death by COVID-19 are considered the factors of COVID-19, with lockdown as a dummy variable. Results: The bound test confirmed the existence of long-run and short-run relationships between variables. Bangladesh's strict lockdown, enforced in reaction to a surge of COVID-19 cases, reduced air pollution and dangerous gas emissions, mainly C O 2 , according to the dynamic multipliers graph.

A Statistical Investigation into the COVID-19 Outbreak Spread.

Objective: Coronavirus-19 (COVID-19) outbreaks have been reported in a range of climates worldwide, including Bangladesh. There is less evidence of a link between the COVID-19 pandemic and climatic variables. This research article's purpose is to examine the relationship between COVID-19 outbreaks and climatic factors in Dhaka, Bangladesh. Methods: The daily time series COVID-19 data used in this study span from May 1, 2020, to April 14, 2021, for the study area, Dhaka, Bangladesh. The Climatic factors included in this study were average temperature, particulate matter ( P M 2 . 5 ), humidity, carbon emissions, and wind speed within the same timeframe and location. The strength and direction of the relationship between meteorological factors and COVID-19 positive cases are examined using the Spearman correlation. This study examines the asymmetric effect of climatic factors on the COVID-19 pandemic in Dhaka, Bangladesh, using the Nonlinear Autoregressive Distributed Lag (NARDL) model. Results: COVID-19 widespread has a substantial positive association with wind speed (r = .781), temperature (r = .599), and carbon emissions (r = .309), whereas P M 2 . 5 (r = -.178) has a negative relationship at the 1% level of significance. Furthermore, with a 1% change in temperature, the incidence of COVID-19 increased by 1.23% in the short run and 1.53% in the long run, with the remaining variables remaining constant. Similarly, in the short-term, humidity was not significantly related to the COVID-19 pandemic. However, in the long term, it increased 1.13% because of a 1% change in humidity. The changes in PM2.5 level and wind speed are significantly associated with COVID-19 new cases after adjusting population density and the human development index.

The Obstacles to Combat against Covid-19 Pandemic and the Remedies: Bangladesh Scenario.

Background: Bangladesh has been going through the austerity of the unique COVID-19 for more than a year like several other nations in the world in spite of concerted efforts taken by the government along with other concerned authorities who have advocated compulsory guidelines involving social distancing procedures accompanied by lockdown to have control over the pandemic. In this paper, the barriers faced by the government to protect people from the COVID-19 pandemic have been investigated. Also, the number of daily infected people against the number of daily tests has been underlined to comprehend the overall pandemic picture in Bangladesh. Design and Methods: A descriptive study has been carried out to investigate the obstacles to tackle the COVID-19 pandemic for this country. The intensity of the outbreaks of the pandemic in this country is stated from March 8, 2020, to February 12, 2021. Secondary data have been employed from different sources to serve the goals of the study. Results: The poor management in the health sector of Bangladesh has been an issue of major concern during the early stage of COVID-19 which incorporates deficiency of medical equipment, lack of facilities for testing COVID-19, poor patient management, and uncertainty in the medication system. Finally, some recommendations have been proposed for the concerned organizations to tackle the current pandemic and as well in the future. Conclusions: To control this COVID-19 pandemic, it is necessary to find the difficulties and discover the remedies which have been done in this paper for the Bangladesh perspective.

Effects of Adipocyte-derived Factors on the Adrenal Cortex.

BACKGROUND AND OBJECTIVE: Obesity is highly complicated by hypertension and hyperglycemia. In particular, it has been proposed that obesity-related hypertension is caused by adipocyte-derived factors that are recognized as undetermined proteins secreted from adipocytes. Adipocyte-derived factors have been known to be related to aldosterone secretion in the adrenal gland. So far, Wnt proteins, CTRP-1, VLDL, LDL, HDL and leptin have been demonstrated to stimulate aldosterone secretion. In contrast, it has not yet been clarified whether adipocyte-derived factors also affect adrenal cortisol secretion. METHODS AND RESULTS: In the present study, we investigated the effect of adipocyte-derived factors on cortisol synthase gene CYP11B1 mRNA expression in vitro study using adrenocortical carcinoma H295R cells and mouse fibroblast 3T3-L1cells. Interestingly, adipocyte-derived factors were demonstrated to have the ability to stimulate CYP11B1 mRNA expression. CONCLUSION: Since CYP11B1 is well known as a limiting enzyme of cortisol synthesis, our study suggests that adipocyte-derived factors may stimulate cortisol secretion, as well as aldosterone secretion. Taken together, adipocyte-derived factors may be the cause of metabolic syndrome due to their stimulating effects on aldosterone/cortisol secretion. Therefore, the innovation of novel drugs against them may possibly be a new approach against metabolic syndrome.

Inhibitory Effects of a Novel PPAR-γ Agonist MEKT1 on Pomc Expression/ACTH Secretion in AtT20 Cells.

Although therapeutic effects of the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists rosiglitazone and pioglitazone against Cushing's disease have been reported, their effects are still controversial and inconsistent. We therefore examined the effects of a novel PPAR-γ agonist, MEKT1, on Pomc expression/ACTH secretion using murine corticotroph-derived AtT20 cells and compared its effects with those of rosiglitazone and pioglitazone. AtT20 cells were treated with either 1 nM~10 µM MEKT1, rosiglitazone, or pioglitazone for 24 hours. Thereafter, their effects on proopiomelanocortin gene (Pomc) mRNA expression were studied by qPCR and the Pomc promoter (-703/+58) activity was demonstrated by luciferase assay. Pomc mRNA expression and promoter activity were significantly inhibited by MEKT1 at 10 µM compared to rosiglitazone and pioglitazone. SiRNA-mediated PPAR-γ knockdown significantly abrogated MEKT1-mediated Pomc mRNA suppression. ACTH secretion from AtT20 cells was also significantly inhibited by MEKT1. Deletion/point mutant analyses of Pomc promoter indicated that the MEKT1-mediated suppression was mediated via NurRE, TpitRE, and NBRE at -404/-383, -316/-309, and -69/-63, respectively. Moreover, MEKT1 significantly suppressed Nur77, Nurr1, and Tpit mRNA expression. MEKT1 also was demonstrated to inhibit the protein-DNA interaction of Nur77/Nurr1-NurRE, Tpit-TpitRE, and Nur77-NBRE by ChIP assay. Taken together, it is suggested that MEKT1 could be a novel therapeutic medication for Cushing's disease.

Endogenous Purification of NR4A2 (Nurr1) Identified Poly(ADP-Ribose) Polymerase 1 as a Prime Coregulator in Human Adrenocortical H295R Cells.

Aldosterone is synthesized in zona glomerulosa of adrenal cortex in response to angiotensin II. This stimulation transcriptionally induces expression of a series of steroidogenic genes such as HSD3B and CYP11B2 via NR4A (nuclear receptor subfamily 4 group A) nuclear receptors and ATF (activating transcription factor) family transcription factors. Nurr1 belongs to the NR4A family and is regarded as an orphan nuclear receptor. The physiological significance of Nurr1 in aldosterone production in adrenal cortex has been well studied. However, coregulators supporting the Nurr1 function still remain elusive. In this study, we performed RIME (rapid immunoprecipitation mass spectrometry of endogenous proteins), a recently developed endogenous coregulator purification method, in human adrenocortical H295R cells and identified PARP1 as one of the top Nurr1-interacting proteins. Nurr1-PARP1 interaction was verified by co-immunoprecipitation. In addition, both siRNA knockdown of PARP1 and treatment of AG14361, a specific PARP1 inhibitor suppressed the angiotensin II-mediated target gene induction in H295R cells. Furthermore, PARP1 inhibitor also suppressed the aldosterone secretion in response to the angiotensin II. Together, these results suggest PARP1 is a prime coregulator for Nurr1.

High glucose stimulates expression of aldosterone synthase (CYP11B2) and secretion of aldosterone in human adrenal cells.

Aldosterone synthase is the key rate-limiting enzyme in adrenal aldosterone production, and induction of its gene (CYP11B2) results in the progression of hypertension. As hypertension is a frequent complication among patients with diabetes, we set out to elucidate the link between diabetes mellitus and hypertension. We examined the effects of high glucose on CYP11B2 expression and aldosterone production using human adrenal H295R cells and a stable H295R cell line expressing a CYP11B2 5'-flanking region/luciferase cDNA chimeric construct. d-glucose (d-glu), but not its enantiomer l-glucose, dose dependently induced CYP11B2 transcription and mRNA expression. A high concentration (450 mg·dL-1) of d-glu time dependently induced CYP11B2 transcription and mRNA expression. Moreover, high glucose stimulated secretion of aldosterone into the media. Transient transfection studies using deletion mutants/nerve growth factor-induced clone B (NGFIB) response element 1 (NBRE-1) point mutant of CYP11B2 5'-flanking region revealed that the NBRE-1 element, known to be activated by transcription factors NGFIB and NURR1, was responsible for the high glucose-mediated effect. High glucose also induced the mRNA expression of these transcription factors, especially that of NURR1, but NURR1 knockdown using its siRNA did not affect high glucose-induced CYP11B2 mRNA expression. Taken together, it is speculated that high glucose may induce CYP11B2 transcription via the NBRE-1 element in its 5'-flanking region, resulting in the increase in aldosterone production although high glucose-induced NURR1 is not directly involved in the effect. Additionally, glucose metabolism and calcium channels were found to be involved in the high glucose effect. Our observations suggest one possible explanation for the high incidence of hypertension in patients with diabetes.

Suppressive effects of RXR agonist PA024 on adrenal CYP11B2 expression, aldosterone secretion and blood pressure.

The effects of retinoids on adrenal aldosterone synthase gene (CYP11B2) expression and aldosterone secretion are still unknown. We therefore examined the effects of nuclear retinoid X receptor (RXR) pan-agonist PA024 on CYP11B2 expression, aldosterone secretion and blood pressure, to elucidate its potential as a novel anti-hypertensive drug. We demonstrated that PA024 significantly suppressed angiotensin II (Ang II)-induced CYP11B2 mRNA expression, promoter activity and aldosterone secretion in human adrenocortical H295R cells. Human CYP11B2 promoter functional analyses using its deletion and point mutants indicated that the suppression of CYP11B2 promoter activity by PA024 was in the region from -1521 (full length) to -106 including the NBRE-1 and the Ad5 elements, and the Ad5 element may be mainly involved in the PA024-mediated suppression. PA024 also significantly suppressed the Ang II-induced mRNA expression of transcription factors NURR1 and NGFIB that bind to and activate the Ad5 element. NURR1 overexpression demonstrated that the decrease of NURR1 expression may contribute to the PA024-mediated suppression of CYP11B2 transcription. PA024 also suppressed the Ang II-induced mRNA expression of StAR, HSD3ß2 and CYP21A2, a steroidogenic enzyme group involved in aldosterone biosynthesis. Additionally, the PA024-mediated CYP11B2 transcription suppression was shown to be exerted via RXRα. Moreover, the combination of PPARγ agonist pioglitazone and PA024 caused synergistic suppressive effects on CYP11B2 mRNA expression. Finally, PA024 treatment significantly lowered both the systolic and diastolic blood pressure in Tsukuba hypertensive mice (hRN8-12 x hAG2-5). Thus, RXR pan-agonist PA024 may be a candidate anti-hypertensive drugs that acts via the suppression of aldosterone synthesis and secretion.

Role of NeuroD1 on the negative regulation of Pomc expression by glucocorticoid.

The mechanism of the negative regulation of proopiomelanocortin gene (Pomc) by glucocorticoids (Gcs) is still unclear in many points. Here, we demonstrated the involvement of neurogenic differentiation factor 1 (NeuroD1) in the Gc-mediated negative regulation of Pomc. Murine pituitary adrenocorticotropic hormone (ACTH) producing corticotroph tumor-derived AtT20 cells were treated with dexamethasone (DEX) (1-100 nM) and cultured for 24 hrs. Thereafter, Pomc mRNA expression was studied by quantitative real-time PCR and rat Pomc promoter (-703/+58) activity was examined by luciferase assay. Both Pomc mRNA expression and Pomc promoter activity were inhibited by DEX in a dose-dependent manner. Deletion and point mutant analyses of Pomc promoter suggested that the DEX-mediated transcriptional repression was mediated via E-box that exists at -376/-371 in the promoter. Since NeuroD1 is known to bind to and activate E-box of the Pomc promoter, we next examined the effect of DEX on NeuroD1 expression. Interestingly, DEX dose-dependently inhibited NeuroD1 mRNA expression, mouse NeuroD1 promoter (-2.2-kb) activity, and NeuroD1 protein expression in AtT20 cells. In addition, we confirmed the inhibitory effect of DEX on the interaction of NeuroD1 and E-box on Pomc promoter by chromatin immunoprecipitation (ChIP) assay. Finally, overexpression of mouse NeuroD1 could rescue the DEX-mediated inhibition of Pomc mRNA expression and Pomc promoter activity. Taken together, it is suggested that the suppression of NeuroD1 expression and the inhibition of NeuroD1/E-box interaction may play an important role in the Gc-mediated negative regulation of Pomc.

Effects of RXR Agonists on Cell Proliferation/Apoptosis and ACTH Secretion/Pomc Expression.

Various retinoid X receptor (RXR) agonists have recently been developed, and some of them have shown anti-tumor effects both in vivo and in vitro. However, there has been no report showing the effects of RXR agonists on Cushing's disease, which is caused by excessive ACTH secretion in a corticotroph tumor of the pituitary gland. Therefore, we examined the effects of synthetic RXR pan-agonists HX630 and PA024 on the proliferation, apoptosis, ACTH secretion, and pro-opiomelanocortin (Pomc) gene expression of murine pituitary corticotroph tumor AtT20 cells. We demonstrated that both RXR agonists induced apoptosis dose-dependently in AtT20 cells, and inhibited their proliferation at their higher doses. Microarray analysis identified a significant gene network associated with caspase 3 induced by high dose HX630. On the other hand, HX630, but not PA024, inhibited Pomc transcription, Pomc mRNA expression, and ACTH secretion dose-dependently. Furthermore, we provide new evidence that HX630 negatively regulates the Pomc promoter activity at the transcriptional level due to the suppression of the transcription factor Nur77 and Nurr1 mRNA expression and the reduction of Nur77/Nurr1 heterodimer recruiting to the Pomc promoter region. We also demonstrated that the HX630-mediated suppression of the Pomc gene expression was exerted via RXRα. Furthermore, HX630 inhibited tumor growth and decreased Pomc mRNA expression in corticotroph tumor cells in female nude mice in vivo. Thus, these results indicate that RXR agonists, especially HX630, could be a new therapeutic candidate for Cushing's disease.

Retinoic acid receptor-α up-regulates proopiomelanocortin gene expression in AtT20 corticotroph cells.

Cushing's disease is a disorder caused by excessive ACTH secretion from a corticotroph tumor of the pituitary gland. Although its standard therapy is a transsphenoidal surgery, innovation of novel medical treatments for the disease is urgently necessary. Retinoic acid (RA) has been reported to suppress adrenocorticotropic hormone (ACTH) secretion in Cushing's disease. However, the role of RA receptor (RAR) in proopiomelanocortin (Pomc) gene expression remains uncertain. We here examined the involvement of RARα in Pomc regulation using AtT20 corticotroph cells. Surprisingly, a synthetic RARα agonist Am80 increased Pomc mRNA expression, CRH-induced ACTH secretion, and Pomc promoter activity. Small interfering RNA-mediated RARα-knockdown suppressed both basal and Am80-induced Pomc promoter activity. RARα-overexpression dose-dependently increased Pomc promoter activity. Pomc promoter mutation analysis revealed that both Tpit and NeuroD1 binding elements were responsible for the Am80-mediated effect. Am80 increased Tpit expression while RAR antagonist LE540 suppressed the increase. Tpit-overexpression increased Pomc promoter activity. Mammalian two-hybrid assay revealed that Am80 induced NeuroD1-RARα interaction. NeuroD1-overexpression enhanced the Am80-induced Pomc promoter activity, which was suppressed by NeuroD1 truncated mutant-overexpression. RARα thus positively regulates ACTH secretion/Pomc gene expression through interaction with NeuroD1 and Tpit expression increase. The present observation will be useful for the future development of the RA/retinoid-derived therapeutics of the disease.

Effect of Fungicides and Plant Extracts on the Conidial Germination of Colletotrichum gloeosporioides Causing Mango Anthracnose.

In Northern Bangladesh, generally mango trees are planted as agroforest that gives higher Net Present Value (NPV) than traditional agriculture. Mango anthracnose caused by Colletotrichum gloeosporioides Penz. is seen as a very destructive and widely distributed disease, which results in poor market value. Five fungicides such as Cupravit, Bavistin, Dithane M-45, Thiovit and Redomil were tested against conidial germination of C. gloeosporioides. Dithane M-45 and Redomil were the most effective when the conidia were immersed for 10~20 minutes at 500~1000 ppm concentrations. Antifungal activities of 13 plant extracts were tested against conidial germination of C. gloeosporioides. Conidial germination of C. gloeosporioides was completely inhibited in Curcuma longa (leaf and rhizome), Tagetes erecta (leaf) and Zingiber officinales (rhizome) after 15 minutes of incubation respectively.