Tumor cell-derived PDGF-B potentiates mouse mesenchymal stem cells-pericytes transition and recruitment through an interaction with NRP-1

<p>Abstract</p> <p>Background</p> <p>New blood vessel formation, or angiogenic switch, is an essential event in the development of solid tumors and their metastatic growth. Tumor blood vessel formation and remodeling is a complex and multi-step processes. The differentiation and recruitment of mural cells including vascular smooth muscle cells and pericytes are essential steps in tumor angiogenesis. However, the role of tumor cells in differentiation and recruitment of mural cells has not yet been fully elucidated. This study focuses on the role of human tumor cells in governing the differentiation of mouse mesenchymal stem cells (MSCs) to pericytes and their recruitment in the tumor angiogenesis process.</p> <p>Results</p> <p>We show that C3H/10T1/2 mouse embryonic mesenchymal stem cells, under the influence of different tumor cell-derived conditioned media, differentiate into mature pericytes. These differentiated pericytes, in turn, are recruited to bind with capillary-like networks formed by endothelial cells on the matrigel under <it>in vitro </it>conditions and recruited to bind with blood vessels on gel-foam under <it>in vivo </it>conditions. The degree of recruitment of pericytes into <it>in vitro </it>neo-angiogenesis is tumor cell phenotype specific. Interestingly, invasive cells recruit less pericytes as compared to non-invasive cells. We identified tumor cell-secreted platelet-derived growth factor-B (PDGF-B) as a crucial factor controlling the differentiation and recruitment processes through an interaction with neuropilin-1 (NRP-1) in mesenchymal stem cells.</p> <p>Conclusion</p> <p>These new insights into the roles of tumor cell-secreted PDGF-B-NRP-1 signaling in MSCs-fate determination may help to develop new antiangiogenic strategies to prevent the tumor growth and metastasis and result in more effective cancer therapies.</p

Cyr61/CCN1 signaling is critical for epithelial-mesenchymal transition and stemness and promotes pancreatic carcinogenesis

<p>Abstract</p> <p>Background</p> <p>Despite recent advances in outlining the mechanisms involved in pancreatic carcinogenesis, precise molecular pathways and cellular lineage specification remains incompletely understood.</p> <p>Results</p> <p>We show here that Cyr61/CCN1 play a critical role in pancreatic carcinogenesis through the induction of EMT and stemness. Cyr61 mRNA and protein were detected in the early precursor lesions and their expression intensified with disease progression. Cyr61/CCN1 expression was also detected in different pancreatic cancer cell lines. The aggressive cell lines, in which the expressions of mesenchymal/stem cell molecular markers are predominant; exhibit more Cyr61/CCN1 expression. Cyr61 expression is exorbitantly higher in cancer stem/tumor initiating Panc-1-side-population (SP) cells. Upon Cyr61/CCN1 silencing, the aggressive behaviors are reduced by obliterating interlinking pathobiological events such as reversing the EMT, blocking the expression of stem-cell-like traits and inhibiting migration. In contrast, addition of Cyr61 protein in culture medium augments EMT and stemness features in relatively less aggressive BxPC3 pancreatic cancer cells. Using a xenograft model we demonstrated that cyr61/CCN1 silencing in Panc-1-SP cells reverses the stemness features and tumor initiating potency of these cells. Moreover, our results imply a miRNA-based mechanism for the regulation of aggressive behaviors of pancreatic cancer cells by Cyr61/CCN1.</p> <p>Conclusions</p> <p>In conclusion, the discovery of the involvement of Cyr61/CCN1 in pancreatic carcinogenesis may represent an important marker for PDAC and suggests Cyr61/CCN1 can be a potential cancer therapeutic target.</p

Psychiatric morbidity among rural and slum female population: A comparative study

Background: Psychiatric disorders are more prevalent among women than men worldwide. The lifetime risk of depres­sion and dysthymia are twice as common in women as men. Rural women usually undergoes more stressful situations and also scores more on stress scale than that of urban and slum population. Objectives: The research objectives of this study are: 1) To find out the prevalence of psychiatric disorders among the study population. 2) To compare the disorders among the rural and slum female population. 3) To find out the influence of existing socio-demographic factors on psychiatric disorders. Method: This is a community-based study, which is also cross sectional and descriptive in nature. The sample for the main study constituted 366 randomly selected respondents. A two-staged screening procedure was carried in the study. First, the total population was studied by screening test-Self Reporting Questionnaire (SRQ) to divide the sample into 'screen positive' and 'screen negative' subjects. In the second stage, full assessment of a mixture of all 'screen positive' and 25% 'screen negative' was carried out by structured clinical interview for diagnosis (SCID-NP). Later SCID filled by the respondents was assessed by consultant psychiatrists by using DSMIV in order to put exact clinical diagnosis. Stress was scored according to Presumptive Stressful Life Events Scale (PSLE). The total duration of the study was from July 2010 to June 2011. Results: Higher prevalence of psychiatric morbidity was found among rural sample (22.8%) than slum (10.90%) population. Regarding pattern of psychiatric disorders among rural sample (22.8%) than slum (10.9%) population.See the PDF for the rest of the abstract

Availability and price changes of potential medicines and equipment for the prevention and treatment of COVID-19 among pharmacy and drug stores in Bangladesh; findings and implications

Objective: There are concerns with increased prices and drug shortages for pertinent medicines and personal protective equipment (PPE) to prevent and treat COVID-19 enhanced by misinformation. Community pharmacists and drug stores play a significant role in disease management in Bangladesh due to high co-payments. Consequently, a need to review prices and availability in the pandemic. Materials and Methods: Multiple approach involving a review and questionnaire among pharmacies and stores early March to end May 2020. Results and Discussion: 170 pharmacies and drug stores took part, giving a response rate of 63.9%. Encouragingly, no change in utilization of antimalarial medicines in 51.2% of stores despite global endorsements. However, increased utilisation of antibiotics (70.6%), analgesics (97.6%), vitamins (90.6%) and PPE (over 95%). Encouragingly, increases in purchasing of PPE. No increase in prices among 50% of the stores for antimalarials, with a similar situation for antibiotics (65.3%), analgesics (54.7%), and vitamins (51.8%). However, price increases typically for PPE (over 90% of stores). Shortages also seen for medicines and PPE, again greater for PPE. Conclusions: The pandemic has impacted on the supply and prices of medicines and PPE in Bangladesh. Key stakeholder groups can play a role addressing misinformation, with enhanced local production helping address future shortages and prices

Rapid assessment of price instability and paucity of medicines and protection for COVID-19 across Asia : findings and public health implications for the future

Background: Countries have introduced a variety of measures to prevent and treat COVID-19 with medicines and personal protective equipment (PPE), with some countries adopting preventative strategies earlier than others. However, there has been considerable controversy surrounding some treatments. This includes hydroxychloroquine where the initial hype and misinformation lead to shortages, price rises and suicides. Price rises and shortages have also been seen for PPE. Such activities can have catastrophic effects on patients where there are high co-payment levels and issues of affordability. Consequently, there is a need to investigate this further. Objective: Assess changes in the availability, utilization and prices of relevant medicines and PPE during the pandemic among a range of Asian countries. Our approach: Narrative literature review combined with interviews among community pharmacists to assess changes in consumption, prices and shortages of medicines and PPE from the beginning of March 2020 until end of May 2020. In addition, suggestions on ways to reduce misinformation. Results: 308 pharmacists took part from five Asian countries. There was an appreciable increase in the utilization of antimicrobials in Pakistan (in over 88% of pharmacies), with lower increases or no change in Bangladesh, India, Malaysia and Vietnam. Encouragingly, there was increased use of vitamins/immune boosters and PPE across the countries, as well as limited price rises for antimicrobials in India, Malaysia and Vietnam, although greater price rises seen for analgesics and vitamin C/immune boosters. Appreciable price increases were also seen for PPE across some countries. Conclusion: Encouraging to see increases in utilization of vitamins/immune boosters and PPE. However, increases in the utilization and prices of antimicrobials is a concern that needs addressing alongside misinformation and any unintended consequences from the pandemic. Community pharmacists can play a key role in providing evidence-based advice, helping to moderate prices, as well as helping address some of the unintended consequences of the pandemic

Ongoing efforts to improve the management of patients with diabetes in Bangladesh and the implications

Background: Prevalence rates of patients with diabetes are growing across countries, and Bangladesh is no exception. Associated costs are also increasing, driven by costs associated with the complications of diabetes including hypoglycaemia. Long-acting insulin analogues were developed to reduce hypoglycaemia as well as improve patient comfort and adherence. However, they have been appreciably more expensive reducing their affordability and use. Biosimilars offer a way forward. Consequently, there is a need to document current prescribing and dispensing rates for long-acting insulin analogues across Bangladesh, including current prices and differences, as a result of affordability and other issues. Methods: Mixed method approach including surveying prescribing practices in hospitals coupled with dispensing practices and prices among community pharmacies and drug stores across Bangladesh. This method was adopted since public hospitals only dispense insulins such as soluble insulins free-of-charge until funds run out and all long-acting insulin analogues have to be purchased from community stores. Results: There has been growing prescribing and dispensing of long-acting insulins in Bangladesh in recent years, accounting for over 80% of all insulins dispensed in a minority of stores. This has been helped by growing prescribing and dispensing of biosimilar insulin glargine at lower costs that the originator, with this trend likely to continue with envisaged growth in the number of patients. Consequently, Bangladesh can serve as an exemplar to other low- and middle-income countries struggling to fund long-acting insulins for their patients. Conclusions: It was encouraging to see continued growth in the prescribing and dispensing of long-acting insulin analogues in Bangladesh via the increasing availability of biosimilars. This is likely to continue benefitting all key stakeholder groups

Psychiatric morbidity among rural and slum female population: A comparative study

Background: Psychiatric disorders are more prevalent among women than men worldwide. The lifetime risk of depres­sion and dysthymia are twice as common in women as men. Rural women usually undergoes more stressful situations and also scores more on stress scale than that of urban and slum population. Objectives: The research objectives of this study are: 1) To find out the prevalence of psychiatric disorders among the study population. 2) To compare the disorders among the rural and slum female population. 3) To find out the influence of existing socio-demographic factors on psychiatric disorders. Method: This is a community-based study, which is also cross sectional and descriptive in nature. The sample for the main study constituted 366 randomly selected respondents. A two-staged screening procedure was carried in the study. First, the total population was studied by screening test-Self Reporting Questionnaire (SRQ) to divide the sample into 'screen positive' and 'screen negative' subjects. In the second stage, full assessment of a mixture of all 'screen positive' and 25% 'screen negative' was carried out by structured clinical interview for diagnosis (SCID-NP). Later SCID filled by the respondents was assessed by consultant psychiatrists by using DSMIV in order to put exact clinical diagnosis. Stress was scored according to Presumptive Stressful Life Events Scale (PSLE). The total duration of the study was from July 2010 to June 2011. Results: Higher prevalence of psychiatric morbidity was found among rural sample (22.8%) than slum (10.90%) population. Regarding pattern of psychiatric disorders among rural sample (22.8%) than slum (10.9%) population. See the PDF for the rest of the abstract