G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

G protein-coupled receptor kinase 2 (GRK2), an important subtype of GRKs, specifically phosphorylates agonist-activated G protein-coupled receptors (GPCRs). Besides, current research confirms that it participates in multiple regulation of diverse cells via a non-phosphorylated pathway, including interacting with various non-receptor substrates and binding partners. Fibrosis is a common pathophysiological phenomenon in the repair process of many tissues due to various pathogenic factors such as inflammation, injury, drugs, etc. The characteristics of fibrosis are the activation of fibroblasts leading to myofibroblast proliferation and differentiation, subsequent aggerate excessive deposition of extracellular matrix (ECM). Then, a positive feedback loop is occurred between tissue stiffness caused by ECM and fibroblasts, ultimately resulting in distortion of organ architecture and function. At present, GRK2, which has been described as a multifunctional protein, regulates copious signaling pathways under pathophysiological conditions correlated with fibrotic diseases. Along with GRK2-mediated regulation, there are diverse effects on the growth and apoptosis of different cells, inflammatory response and deposition of ECM, which are essential in organ fibrosis progression. This review is to highlight the relationship between GRK2 and fibrotic diseases based on recent research. It is becoming more convincing that GRK2 could be considered as a potential therapeutic target in many fibrotic diseases.

Presence of Malassezia Hyphae Is Correlated with Pathogenesis of Seborrheic Dermatitis

Our results support the proposal that the hyphal form of Malassezia could be one of the pathogenic factors that contribute to SD, which has been previously less well studied. This clinical observation paves the way for further investigations of the molecular mechanisms of Malassezia hyphal pathogenicity in SD.

Discovery of Therapeutic Candidates for Diabetic Retinopathy Based on Molecular Switch Analysis: Application of a Systematic Process

The pathogenesis of diabetic retinopathy (DR) is complicated, and there is no effective drug. Oxidative stress-induced human retinal microvascular endothelial cells (HRMECs) injury is one of the pathogenic factors for DR. Molecular switches are considered high-risk targets in disease progression. Identification of molecular switch is crucial to interpret the pathogenesis of disease and screen effective ingredients. In this study, a systematic process was executed to discover therapeutic candidates for DR based on HRMECs injury. First of all, the molecular mechanism of HRMECs oxidative stress injury was revealed by transcriptomics and network pharmacology. We found that oxidative stress was one of the pivotal pathogenic factors, which interfered with vascular system development, inflammation, cell adhesion, and cytoskeleton damaged HRMECs through crosstalk. Then, network topology analysis was used to recognize molecular switches. The results indicated that the Keap1-Nrf2-ARE signaling pathway was the molecular switch in HRMECs oxidative stress injury. On this basis, the HEK293-ARE overexpression cell line was applied to obtain 18 active traditional Chinese medicine (TCM) ingredients. Furthermore, andrographolide, one of the 18 candidates, was applied in the HRMECs oxidative stress model to evaluate the accuracy of the systematic process. The efficacy evaluation results showed that andrographolide could regulate oxidative stress, vascular system development, inflammation, adhesion, and skeleton tissue to inhibit HRMECs injury cooperatively. And its mechanism was related to the Nrf2 signaling pathway. Overall, our data suggest that the Nrf2 signaling pathway is the molecular switch in the HRMECs oxidative stress injury. 18 potential Nrf2 agonists are likely to be promising DR candidates.

Feline pulmonary nematodes; new challenges for veterinary practitioners

Pulmonary parasitic diseases have become a frequent feline condition. Aelurostrongylus abstrusus, Troglostrongylus brevior and Capillaria aerophila appear to be the main pathogenic factors. Felines that are affected may display respiratory as well as non-specific symptoms. Diagnostic methods include copromicroscopic, serological and molecular detection, whereas the treatment should be both symptomatic and elective.

A comparative clinical study of Khanda Shunthi and Prasarni Avaleha in the Management of Ama Vata w.s.r. to Rheumatoid Arthritis

Rheumatoid Arthritis is a chronic inflammatory joint disease characterized by swollen, painful and stiff joints. Amavata is a disease of Madhyama Roga Marga as it affects Sandhis and Haridaya Marma. Though Ama and Vata are the predominant pathogenic factors but the disease represents Tridoshic vitiation. The affliction of Sandhis by Vata dosha in association with Ama reflects the equal role of both Dosha and Dushya in the causation of disease. Moreover, the chief pathogenic factors, being contradictory in nature possess difficulty in planning the line of treatment. The objectives of this randomized parallel group comparative study were to evaluate the effect of Khanda Shunthi and Prasarni Avaleha in the management of Amavata. This Study was conducted on 40 patients selected randomly from OPD and IPD of Desh Bhagat Ayurvedic Hospital and divided into 2 trial groups A and B having 20 patients in each group. Group A received Khanda Shunthi 10 gms BD and Group B received Prasarni Avaleha 10 gms BD with lukewarm water for 60 days. Results showed statistically significant difference in effect of Group A and Group B on, Pain, Swelling, Stiffness, ESR, Walking time and Grip Strength except on Fever and HB. Percent wise Khanda Shunthi is found to be more effective than Prasarni Avaleha for all assessment criteria in the management of Amavata.

Hearing Loss in Beta-Thalassemia: Systematic Review

In the last half century, the life expectancy of beta-thalassemia patients has strikingly increased mostly due to regular blood transfusions and chelation treatments. The improved survival, however, has allowed for the emergence of comorbidities, such as hearing loss, with a non-negligible impact on the patients’ quality of life. This thorough review analyzes the acquired knowledge regarding hearing impairment in this hereditary hemoglobinopathy, aiming at defining its prevalence, features, course, and possible disease- or treatment-related pathogenic factors. Following PRISMA criteria, we retrieved 60 studies published between 1979 and 2021. Diagnostic tools and criteria, forms of hearing impairment, correlations with beta-thalassemia phenotypes, age and sex, chelation treatment and laboratory findings including iron overload, were carefully searched, analyzed and summarized. In spite of the relatively high number of studies in the last 40 years, our knowledge is rather limited, and large prospective studies with homogeneous diagnostic tools and criteria are required to define all the aforementioned issues. According to the literature, the overall prevalence rate of hearing impairment is 32.3%; age, sex, and laboratory findings do not seem to correlate with hearing deficits, while the weak relationship with clinical phenotype and chelation treatment seems to highlight the presence of further yet to be identified pathogenic factors.

Antimicrobial Effect of a Proteolytic Enzyme From the Fruits of Solanum granuloso-leprosum (Dunal) Against Helicobacter pylori

Helicobacter pylori is a gram-negative, helix-shaped, and microaerophilic bacteria that colonizes the human gastric mucosa, causing chronic infections, gastritis, peptic ulcer, lymphomas associated with lymphoid mucosa tissue, and gastric cancer. H. pylori is considered a Type 1 human carcinogen by WHO. The prevalence of the infection is estimated in more than half of the world population. Treatment of H. pylori infection includes antibiotics and proton pump inhibitors, but the increasing antibiotic resistance promotes the research of novel, more effective, and natural antibacterial compounds. The aim of this work was to study the effect of the partially purified proteolytic extract (RAP) of the fruits from Solanum granuloso-leprosum (Dunal), a South American native plant, and a purified fraction named granulosain I, against H. pylori, to obtain natural food additives for the production of anti-H. pylori functional foods. Furthermore, granulosain I and RAP could be used as natural adjuncts to conventional therapies. Granulosain I and RAP antibacterial activity was evaluated as minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against H. pylori NCTC 11638 (reference strain) and twelve H. pylori wild strains, using a microdilution plating technique (Clinical and Laboratory Standards Institute). All the strains tested were susceptible to granulosain I with MIC from 156.25 to 312.5 μg/mL and MBC from 312.5 to 625 μg/mL, respectively. Besides, all the strains tested were susceptible to the RAP with MIC from 312.5 to 625 μg/mL and MBC from 625 to 1,250 μg/mL, respectively. The effect of granulosain I and RAP on the transcription of H. pylori genes encoding pathogenic factors, omp18, ureA, and flaA, with respect to a housekeeping gene (16S rRNA), was evaluated by RT-PCR technique. The band intensity between pathogenic factors and control gene was correlated under treated or untreated conditions, using the ImageJ program. Granulosain I and RAP significantly decreased the expression of pathogenic factors: omp18, ureA, and flaA. The combined inhibitory effect of granulosain I or RAP and an antibiotic such as, amoxicillin (AML, 10 μg), clarithromycin (CLA, 15 μg), levofloxacin (LEV, 5 μg), and metronidazole (MTZ, 5 μg) was evaluated, using the agar diffusion technique. Granulosain I and RAP showed significant synergistic effect on AML, CLA, and LEV, but no significant effect on MTZ was observed. Besides, granulosain I and RAP did not show toxicological effects at the concentrations studied. Finally, granulosain I and RAP could be used as safe natural food additives and as adjuvants for conventional therapies against H. pylori.

Understanding Pattern Hair Loss—Hair Biology Impacted by Genes, Androgens, Prostaglandins and Epigenetic Factors

Pattern hair loss (PHL) is the most frequent cause of hair loss in men and women, accounting for 65% of consultations in a hair referral center. PHL is understood to represent a hereditary, age-dependent progressive thinning of the scalp hair, which follows distinct clinical patterns with notable differences depending on sex and age of onset. Clinical and investigative advances have helped us to understand some of the pathogenic steps, leading to PHL. Besides genetic factors and peculiarities of androgen metabolism, additional pathogenic factors that are suspected include microbiomata, oxidative stress, and microinflammation. While further suspects are likely to be exposed, individual diversity of causal agents, as well as of the sequence of events, or combined factors, must be kept in mind. A large number of therapeutic molecules claimed to be active and patented in this field, and their limited efficacy in offering a definitive cure of PHL confirm the complexity of PHL. The aim of therapy is to retard progression of hair thinning and increase hair coverage of the scalp. As yet, two FDA-approved drugs are available for this purpose, oral finasteride, and topical solution of minoxidil. Variations in posology and formulation allow for an enhancement of patient comfort and treatment efficacy. Antiandrogen treatments in women with normal androgen levels have questionable efficacy while having health risks.