Autophagy, Pyroptosis, and Ferroptosis: New Regulatory Mechanisms for Atherosclerosis

Atherosclerosis is a chronic inflammatory disorder characterized by the gradual buildup of plaques within the vessel wall of middle-sized and large arteries. The occurrence and development of atherosclerosis and the rupture of plaques are related to the injury of vascular cells, including endothelial cells, smooth muscle cells, and macrophages. Autophagy is a subcellular process that plays an important role in the degradation of proteins and damaged organelles, and the autophagy disorder of vascular cells is closely related to atherosclerosis. Pyroptosis is a proinflammatory form of regulated cell death, while ferroptosis is a form of regulated nonapoptotic cell death involving overwhelming iron-dependent lipid peroxidation. Both of them exhibit distinct features from apoptosis, necrosis, and autophagy in morphology, biochemistry, and genetics. However, a growing body of evidence suggests that pyroptosis and ferroptosis interact with autophagy and participate in the development of cancers, degenerative brain diseases and cardiovascular diseases. This review updated the current understanding of autophagy, pyroptosis, and ferroptosis, finding potential links and their effects on atherogenesis and plaque stability, thus providing ways to develop new pharmacological strategies to address atherosclerosis and stabilize vulnerable, ruptured plaques.

A CRITICAL REVIEW ON PUSHKARMOOLADI YOGA IN SHWASA ROGA

Shwasa is a disease of Pranavaha strotas. It is clinically correlated with bronchial asthma. Symptoms of Shwasa are nearly similar to Bronchial Asthma, a chronic inflammatory disorder of the airways. Pushkarmoladi yoga is described in Yoga Ratnakara and Bhaishjya Ratnavali. This yoga contains Pushkarmoola, Pippali, Dhanvayasa, Karkatshringi and Ativisha. This study was conducted to know the efficacy of Pushkarmoola diyoga in Shwasa (Bronchial Asthma). The literary review was performed by a collection of material related to the clinical efficacy of Pushkarmooladiyoga with the help of several essential Ayurvedic and Modern textbooks, Research papers and journals. Pushkarmooladi yoga shows bronchodilator property by relaxation of bronchial smooth muscles and antimicrobial activity against various gram +ve and gram-ve bacteria, which are responsible for Shwasa and have antioxidant properties due to the presence of the particular phenolic compound in its ingredients.

Kimura Disease of the Parotid Gland: Management Approach

Here we present a 43-years old Malay man with Kimura’s disease of the right parotid gland. Asian men have a predisposition for this chronic inflammatory disorder of unknown etiology mostly presenting at the head and neck region. The management in dealing with this patient is not straight forward as the presentation mimics a subcutaneous tumor-like mass in which main differential diagnosis includes lymphoproliferative disorders and parotid neoplasm. Moreover, cytological investigation is inadequate, and this necessitates the use intra-operative frozen section prior to tumor debulking. Without proper investigation, misdiagnosis can occur and potentially expose the patient to unnecessary extensive surgical procedures. Here we discuss step by step approach in managing this patient.

Kimura Disease as a Rare Cause of Proptosis: A Case Report

Kimura disease (KD) is a rare chronic inflammatory disorder of unknown aetiology that primarily affects the head and neck region with lymph node involvement. Young to middle-aged adult Asian males are predominantly affected. The most common presentation is painless subcutaneous swelling in the head and neck region, while proptosis or orbital involvement is very rarely reported. KD shares some features with other inflammatory and neoplastic disorders, including lymphoma; thus, investigations to confirm the diagnosis should not be delayed. Systemic corticosteroids are commonly used to treat KD and show an excellent response; however, the optimal treatment is still uncertain, and KD has a high recurrence rate. We describe the case of a patient with KD who presented with proptosis and post-auricular swelling, which responded well to oral prednisolone treatment.

Relaxation Effect of Extract Ethanol Curcuma Longa on Isolated Guine Pig Trachea

Aims: Asthma is a chronic obstructive pulmonary disease which is a world health problem that is not only infected in developed countries but also in developing countries. According to the National Asthma Education and Prevention Program (NAEPP), asthma can be defined as a chronic inflammatory disorder that occurs in the airways, which involves inflammatory cells. curcumin reduces allergic airway inflammation in mice through inhibition of a specific pathway aimed at investigating the anti-inflammatory effect of curcumin in acute allergic asthma and its underlying mechanisms in mice. Study Design: This study is experimental study. Methodology: The experimental animals were divided into 2 groups, each group consisting of 4 animals. Group 1 gave theophline as a positive control group and group 2 was given extracts with concentrations (1 mg / ml, 2 mg / ml, 3 mg / ml, 4 mg / ml, 5 mg / ml, 6 mg / ml, 7 mg / ml and 8 mg / ml). These animals are acclimatized for 1 (one) week with the aim of homogenizing their food and life with the same conditions so that they are considered eligible for research. Results: The ethanol extract of curcuma longa has no different ability from atropine sulfate 1 x 10-6 M in reducing the smooth muscle contraction of isolated guinea pig tracheal induced by acetylcholine, the strength of acetylcholine without incubation contraction compared to acetylcholine with EETH incubation showed statistically different results (p<0.05). Conclusion: The mechanism of the relaxing effect of curcuma longa on isolated mouse smooth muscle is mediated through inhibition of the PDE enzyme.

Dysregulation of Angiogenesis and Inflammatory Genes in Endometrial Mesenchymal Stem Cells and Their Contribution to Endometriosis

Endometriosis is a common, chronic, inflammatory disorder in women, characterized by the presence of endometrial tissue outside the uterus cavity. The disease affects ~10% of women during their reproductive age. There are some debates on the pathogenesis of endometriosis and its mechanism among scientists; therefore, different hypotheses have been suggested. According to Sampson's theory, a possible mechanism for seeding ectopic endometriotic lesions is a dysregulation of endometrial mesenchymal stem cells (eMSCs). In the present study, we evaluated the expression of candidate genes in eMSCs obtained from endometriosis patients and compared them with non-endometriosis female patients. In addition, bioinformatic analysis was conducted to uncover the genes in the list of our co-expression gene network in endometriosis. According to our results, the expression of vascular endothelial growth factor A, C-X-C-motif chemokine ligand 8, interleukin-6, and intercellular adhesion molecule-1 genes were up-regulated in the eMSCs isolated from endometriosis patients. There was no significant difference in the expression of the LaminB1 gene between the endometriosis and non-endometriosis patients. On the other hand, our bioinformatics analysis demonstrated that co-expressed genes were enriched in the cytokine signaling pathway. Our study provides valuable insights into the gene expression dysregulation in eMSCs derived from endometriosis patients and suggests a possible function for co-expressed networks in the pathogenesis of endometriosis. To confirm the results, more investigations are required.

Comparison of Bacterial Composition, Concentration, and Metabolism of Short Chain Fatty Acid in Inflammatory Bowel Disease: A Systematic Review

Inflammatory bowel disease (IBD), which consists of Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the intestine. The etiology is heterogeneous and multifactorial, including genetic susceptibility, immune-mediated tissue damage, and changes of lumen microenvironment, especially short-chain fatty acid (SCFA) producing bacteria. Several studies reported a decrease in SCFA concentration in both CD and UC. In fact, SCFAs has important roles in accelerating disease remission. This systematic review aimed to evaluate the changes in SCFA concentration, the composition of SCFA-producing bacteria, and SCFA metabolism in IBD. A literature search was conducted via PubMed, Scopus, and CENTRAL by selecting studies according to inclusion and exclusion criteria. The quality and risk of bias assessment were performed using the Newcastle-Ottawa Scale (NOS). Overall, 160 UC and 127 CD patients from 5 studies were reviewed. The SCFA concentration was significantly reduced (p <0.05) in both PC and UC. Moreover, there was a decrease in major SCFA-producing bacteria. Clostridium coccoides were significantly decreased in the feces of active UC (p = 0.015) and CD (p = 0.04). Clostridium leptum was decreased on intestinal mucosal biopsy of active CD and UC (p <0.0001). Faecalibacterium prausnitzii were decreased in active CD faeces (p <0.0001) and UC (p = 0.0001). Butyrate oxidation rate was also reported to decrease in UC compared to control (p<0.0001). In conclusion, the ability of major SCFA-producing bacterial production in IBD was diminished, which implies a decreased protective and anti-inflammatory effect of SCFA that altered its metabolism.

Journey through Crohn’s Disease Complication: From Fistula Formation to Future Therapies

Crohn’s Disease (CD) is a chronic inflammatory disorder in which up to 50% of patients develop fistula within 20 years after the initial diagnosis, and half of these patients suffer perianal fistulizing disease. The etiopathogenesis of CD-related perianal fistula is still unclear, and its phenotypical and molecular characteristics are even more indefinite. A better understanding would be crucial to develop targeted and more effective therapeutic strategies. At present, the most accredited theory for the formation of CD-related fistula identifies the epithelial-to-mesenchymal transition (EMT) as the driving force. It has been well recognized that CD carries an increased risk of malignancy, particularly mucinous adenocarcinoma is often associated with long-standing fistula in CD patients. Despite the availability of multiple treatment options, perianal fistulizing CD represents a therapeutic challenge and is associated with an important impact on patients’ quality of life. To date, the most effective management is multidisciplinary with the cooperation of gastroenterologists, surgeons, radiologists, and nutritionists and the best recommended treatment is a combination of medical and surgical approaches.

The Influence of Rheumatoid Arthritis on Work Productivity among a Sample of Iraqi Patients

Background: Rheumatoid Arthritis (RA) is a chronic inflammatory disorder that impact daily life activities. The impact on work productivity is critical because of persistent work disability. Aim: To evaluate work productivity in RA patients compared to healthy controls, and to assess the impact of socio-demographic characteristics on work productivity. Methods: This was a case-control study conducted at the Rheumatology Unit of Baghdad Teaching Hospital, Medical City during the period from August 2020 to the end of March 2021. Seventy-two patients with RA were selected and compared with 72 healthy subjects as a control group. All patients were diagnosed according to ACR/EULAR 2010 RA classification criteria. The socio-demographic and clinical features, lifestyle practices, and disease activity of the patients and controls were all recorded during interviews. A standardized Arabic version of the Workplace Activity Limitation Scale (WALS) and the Job Limitations Questionnaire were used to assess the impact of RA on work productivity (WLQ-25). Results: The vast majority of patients were females (58.1%). Positive rheumatoid factor was reported in 94.4% of the patients. The patients showed a significantly lower WALS total score and higher WLQ-25 total score median (IQR) compared with controls. Conclusion: Active RA impairs the work productivity which was influenced by CDAI score and negatively associated with the use of DMARDs.

A CASE OF NEUROPSYCHIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS (NPSLE) PRESENTED WITH NEGATIVE SYMPTOMS OF SCHIZOPHRENIA

Systemic lupus erythematosus is an autoimmune chronic inflammatory disorder affecting connective tissues of body organs. It is more common in female. Neuropsychiatric manifestations like headache, cerebrovascular events like stroke, seizures, psychosis, cognitive impairment, which is termed as neuropsychiatric systemic lupus erythematosus 1,2,3 (NPSLE)