ROLE OF SUBSTANCE P IN PANCREATITIS AND ASSOCIATED DISEASES

Substance P (SP) is a neuropeptide that has its place in the tachykinin family and helps in the transmission of neurogenic signals. SP is also a neuromodulator that plays a crucial part in pain during inflammatory processes. It is produced by the capsaicin-sensitive unmyelinated C fibers sensory neurons by the central and peripheral nervous systems. Substance P is known as a critical primary responder to most of the extreme stimuli, i.e., specifically those with the ability to destabilize the biological integrity. Hence, SP can be considered as an instantaneous system for defense, stress, healing, etc. SP is known to perform a vital role in neurogenic inflammation and the pathophysiology of acute pancreatitis. Out of these, neurogenic inflammation is responsible for acute interstitial pancreatitis as a result of oedema. SP binds itself to the G-protein coupled neurokinin-1 receptor and causes plasma leakage, cell proliferation, and invasion resulting in pancreatic cancer. SP along with comparable neuropeptides seems to be crucial targets with the capability of satisfying several unfulfilled medical requisites. This review article mainly focuses on compiling the available evidence to show that SP could be a novel therapeutic target for pancreatic diseases, and more exploration into the SP signaling pathways is the call of the hour

Inhibition of cystathionine-γ-lyase-mediated hydrogen sulfide production in LPS-stimulated RAW 264.7 macrophages by polyherbal extract

111-117The polyherbal formulation chandraprabha vati (CV) comprising 29 herbs is traditionally used as an anti-inflammatory agent for arthritis and urinary ailments in Indian Siddha medicine. Earlier, we reported that lipopolysaccharide (LPS) induced apoptosis in RAW 264.7 macrophages is mediated by hydrogen sulfide (H2S), a potential target for many inflammatory diseases. Here, we hypothesized that pretreatment with CV decreases H2S level and thereby alleviate the inflammatory conditions induced by LPS in RAW 264.7 macrophages, and this protective effect occurs through alterations in cystathionine-γ-lyase (CSE), a H2S synthesizing enzyme. Accordingly, we evaluated the anti-inflammatory effect of CV in LPS-stimulated RAW 264.7 macrophages in vitro. The CV pretreatment followed by 12 h of LPS-stimulation showed significantly decreased TNF-α, H2S production possibly through CSE gene expression and NF-кB activation compared to the non pretreated macrophages. Our results further confirm that the polyherbal extract chandraprabha vati may be a useful therapy for inflammatory disorders by reducing H2S levels

Inhibition of cystathionine-γ-lyase-mediated hydrogen sulfide production in LPS-stimulated RAW 264.7 macrophages by polyherbal extract

The polyherbal formulation chandraprabha vati (CV) comprising 29 herbs is traditionally used as an anti-inflammatory agent for arthritis and urinary ailments in Indian Siddha medicine. Earlier, we reported that lipopolysaccharide (LPS) induced apoptosis in RAW 264.7 macrophages is mediated by hydrogen sulfide (H2S), a potential target for many inflammatory diseases. Here, we hypothesized that pretreatment with CV decreases H2S level and thereby alleviate the inflammatory conditions induced by LPS in RAW 264.7 macrophages, and this protective effect occurs through alterations in cystathionine-γ-lyase (CSE), a H2S synthesizing enzyme. Accordingly, we evaluated the anti-inflammatory effect of CV in LPS-stimulated RAW 264.7 macrophages in vitro. The CV pretreatment followed by 12 h of LPS-stimulation showed significantly decreased TNF-α, H2S production possibly through CSE gene expression and NF-кB activation compared to the non pretreated macrophages. Our results further confirm that the polyherbal extract chandraprabha vati may be a useful therapy for inflammatory disorders by reducing H2S levels

In vitro and in vivo evaluation of the biofilm-degrading Pseudomonas phage Motto, as a candidate for phage therapy

Infections caused by Pseudomonas aeruginosa are becoming increasingly difficult to treat due to the emergence of strains that have acquired multidrug resistance. Therefore, phage therapy has gained attention as an alternative to the treatment of pseudomonal infections. Phages are not only bactericidal but occasionally show activity against biofilm as well. In this study, we describe the Pseudomonas phage Motto, a T1-like phage that can clear P. aeruginosa infections in an animal model and also exhibits biofilm-degrading properties. The phage has a substantial anti-biofilm activity against strong biofilm-producing isolates (n = 10), with at least a twofold reduction within 24 h. To demonstrate the safety of using phage Motto, cytotoxicity studies were conducted with human cell lines (HEK 293 and RAW 264.7 macrophages). Using a previously established in vivo model, we demonstrated the efficacy of Motto in Caenorhabditis elegans, with a 90% survival rate when treated with the phage at a multiplicity of infection of 10

Assessment of factors related to poly cystic ovarian syndrome – A comparative and correlational study

AbstractPolycystic ovarian syndrome (PCOS) is a common endocrine disorder that primarily affects women of reproductive age. It is particularly prevalent among adolescent females who receive an insufficient diagnosis despite having potentially adverse consequences. The use of PCOS screening questionnaires has the potential to aid in the early detection of symptoms. The goal of this study is to observe if a self-administered questionnaire may be useful for a clear cognizance of the associated conditions like mental stress and menstrual characteristics correlated to polycystic ovary syndrome. In this study, we selected women within an age group of 17–40 with and without PCOS based on the modified Rotterdam criteria to fill out a self-administrated questionnaire based on the signs and symptoms of PCOS majorly focusing on mental stress and menstrual characteristics. SPSS software, univariate analyses were employed to elucidate the associations among the components of PCOS, demographic factors, and lifestyle characteristics, hence providing insights into the interrelationships among those variables. 64 women with PCOS and 141 women without PCOS participated in the present study. The present study revealed PCOS is greatly influenced by age at menarche (p-value= .043), typical cycle length (p-value = .000) mental health problems during menstruation (p-value = .032), and body mass index (p-value = .001). Multivariate hierarchical logistic regression analysis showed only 2 variables BMI (a-OR 1.156,95% CI (1.067–1.242), p-value = .000), and typical cycle length (a-OR 2.278, 95% CI (1.079–4.809), p-value = .003) were significant. The present study showed that BMI and menstrual cycle length were most closely associated with the incidence of PCOS, which is important in diagnosing and treating the condition. Considering the high incidence of PCOS among women of reproductive age and its potential for significant health implications, it would be prudent to incorporate inquiries regarding mental health concerns and menstrual patterns into routine medical assessments for this demographic analysis. This approach aims to ascertain whether additional diagnostic evaluations and screenings for PCOS are warranted

Inhibition of cystathionine-γ-lyase-mediated hydrogen sulfide production in LPS-stimulated RAW 264.7 macrophages by polyherbal extract

The polyherbal formulation chandraprabha vati (CV) comprising 29 herbs is traditionally used as an anti-inflammatory agent for arthritis and urinary ailments in Indian Siddha medicine. Earlier, we reported that lipopolysaccharide (LPS) induced apoptosis in RAW 264.7 macrophages is mediated by hydrogen sulfide (H2S), a potential target for many inflammatory diseases. Here, we hypothesized that pretreatment with CV decreases H2S level and thereby alleviate the inflammatory conditions induced by LPS in RAW 264.7 macrophages, and this protective effect occurs through alterations in cystathionine-γ-lyase (CSE), a H2S synthesizing enzyme. Accordingly, we evaluated the anti-inflammatory effect of CV in LPS-stimulated RAW 264.7 macrophages in vitro. The CV pretreatment followed by 12 h of LPS-stimulation showed significantly decreased TNF-α, H2S production possibly through CSE gene expression and NF-кB activation compared to the non pretreated macrophages. Our results further confir

LPS-induced apoptosis is partially mediated by hydrogen sulphide in RAW 264.7 murine macrophages

Abstract Lipopolysaccharide (LPS) induces apoptosis in murine macrophages through the autocrine secretion of tumor necrosis factor (TNF)-α and nitric oxide (NO). LPS-induced inflammation in murine macrophages is associated with hydrogen sulfide (H2S) production. In this present study, we reported the novel role of H2S in LPS-induced apoptosis and its underlying molecular mechanism specifically at late phases in murine macrophage cells. Stimulation of RAW 264.7 macrophages with LPS resulted in a time- and dose-dependent induction of apoptosis. We observed that the LPS-induced early apoptosis (associated with TNF-α secretion) in macrophages was not inhibited in the presence of H2S inhibitor (DL-propargylglycine), whereas early apoptosis was absent in the presence of TNF receptor antibody. Interestingly, LPS-induced late apoptosis paralleled with H2S production was reduced in the presence of H2S inhibitor but not with TNF receptor antibody. The late apoptotic events mediated by H2S and not the TNF-α induced early apoptosis correlated significantly with the induction of p53 and Bax expression in LPS-induced macrophages. Thus, it is possible that RAW 264.7 murine macrophages treated with LPS mediated early apoptosis through TNF-α and the late apoptotic events through the production of H2S

In vitro and in vivo evaluation of the biofilm-degrading Pseudomonas phage Motto, as a candidate for phage therapy

Infections caused by Pseudomonas aeruginosa are becoming increasingly difficult to treat due to the emergence of strains that have acquired multidrug resistance. Therefore, phage therapy has gained attention as an alternative to the treatment of pseudomonal infections. Phages are not only bactericidal but occasionally show activity against biofilm as well. In this study, we describe the Pseudomonas phage Motto, a T1-like phage that can clear P. aeruginosa infections in an animal model and also exhibits biofilm-degrading properties. The phage has a substantial anti-biofilm activity against strong biofilm-producing isolates (n = 10), with at least a twofold reduction within 24 h. To demonstrate the safety of using phage Motto, cytotoxicity studies were conducted with human cell lines (HEK 293 and RAW 264.7 macrophages). Using a previously established in vivo model, we demonstrated the efficacy of Motto in Caenorhabditis elegans, with a 90% survival rate when treated with the phage at a multiplicity of infection of 10