Current Molecular Medicine - Volume 22, Issue 5, 2022

Background: Inversion of chromosome 9 (inv[9]) is known as one of the most common structural balanced chromosomal variations. Chromosome 9 is highly susceptible to structural rearrangements, specifically to pericentric inversions. Various investigators have posited that inv(9) with different breakpoints could be the cause of several abnormal conditions in individuals, whereas others have considered it a benign variant. To our knowledge, a consensus regarding the effects of this inversion has yet to emerge. Objective: This study aims to discuss the pathogenic/benign effects of inv(9) in all possible clinical conditions detected in the occurrence of this abnormality. Methods: Studies on inv(9) were collected via PubMed, MalaCards, Google Scholar, and NORD, along with the search terms of inv(9), pericentric inv(9), and chromosome 9 variants. Additionally, the incidence of inv(9) and the karyotype and clinical findings of individuals reported with this variant were investigated. Results: The collection of the studies reviewed shows that inv(9) is associated with various conditions such as congenital anomalies, growth retardation, infertility, recurrent pregnancy loss, and cancer. The clinical features associated with this variant in humans vary between growth stages. Further, there have been no shared clinical findings in a specific period. Conclusion: Although there is no conclusive evidence for the pathogenicity of this rearrangement, prenatal genetic counseling on inv(9) and further clinical and molecular studies would be helpful in chromosome 9-related problems.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by an ectopic accumulation of lipids in at least 5% of hepatocytes. The first phase of the disease, called hepatic steatosis, progresses over time to chronic conditions, such as steatohepatitis, cirrhosis, and finally, hepatic insufficiency and cancer. The accumulation of free fatty acids in hepatocytes, particularly saturated fatty acids, is a key process in the development and progression of NAFLD. Furthermore, the accumulation of oxidative stress markers in NAFLD is closely linked to lipotoxicity due to impaired lipid metabolism and increased generation of reactive oxygen species (ROS). However, endogenous mechanisms are activated early in the liver to protect against lipotoxicity and oxidative stress, thus preventing liver mass loss and disease progression. Thus, in order to develop appropriate therapies, the purpose of this review is to discuss recent data from the literature regarding the importance of intrinsic mechanisms deployed by the liver in protecting itself against the adverse effects related to chronic lipid accumulation and ROS generation.

Recently, remarkable advances have been achieved in the molecular biopathology field and researchers turned to evaluate the role, molecular mechanisms, and clinical value of transcription factors in curing a variety of parenchymal degenerative pathologies. Special agents have the capability to cell lineage reprogramming termed transcription factors with a capacity for gene expression modification. Therefore, whatever niche factor may modify gene expression is termed as a transcription factor. A variety of transcription factors have been identified to participate in the regulation of pancreatic stem cell maturation, differentiation, and proliferation; primarily, not only Pdx1, NeuroG3, and MafA, but transcription factors can also transdifferentiate somatic cells in between, liver and gallbladder cells into insulin-producing cells. These heterogenic capabilities of the transcription factors are of clinical significance since they can control cells' regeneration capacity. Physiologically, the pancreatic cells are subdivided into exocrine and endocrine cells. Pancreatic endocrine dysfunction is clinically more common and of more clinical relevance. The paper will illustrate the role and possible mechanisms of transcription factors in the transdifferentiation of endodermderived somatic cells into pancreatic beta-like cells. Clinically, understanding the potential mechanisms in generating physiologic beta cells is extremely crucial to optimize current therapies and evaluate new therapeutic targets via recruiting specific transcription factors. The transcription factors can be applied to both types of diabetes and chronic pancreatitis.

Various traditional herbal plants have been associated with unique pharmacological actions. Natural parts as well as processed plant parts are known to possess gastro-protective and gastro- mucosal healing property. Motive of this review analysis is to explain the gastro-protective and gastro-mucosal healing property of different herbal plants and their constituents indigenous to various regions of the globe and elucidate mechanisms of the healing by their metabolic extracts. Moreover, an attempt shall be made to explicate the possible molecular pharmacological targets responsible for healing gastric ulcer activity. A thorough survey of literature has been carried out from various scientific resources and using keywords like peptic ulcer mechanism, gastro-protective agents, gastro-mucosal healing property, natural and processed herbal drugs preventing peptic ulcers. This article will present a running commentary on the prospects and potential of herbal plants exhibiting gastroprotective activity and gastro-mucosal healing property.

Objective: Psoriasis is a chronic inflammatory skin disease highly depending on angiogenesis. Our prior results showed that the mRNA and protein of Del-1 in dermal mesenchymal stem cells (dMSCs) was up-regulated from psoriasis. Our aim was further to investigate the role of Del-1 from dMSCs in the pathogenesis of psoriasis and confirm the effect of Del-1 on the pathogenesis of psoriasis. Methods: We conducted an immunohistochemistry experiment to further investigate the expression of Del-1in psoriatic lesions. In addition, dMSCs with over-expressed Del-1 via the lentiviral vector of Del-1 were co-cultured with ECs, and the protein expression of integrins (αvβ3, αvβ5 ,and α5β1) of ECs were detected by western blotting. Results: This research showed that Del-1 was significantly increased in lesions of patients with psoriasis (p< .05, 9.96 vs. 2.18), and Del-1 from dMSCs successfully induced up-regulation of integrins α5β1 and αvβ3 (all p < .05). Conclusion: This study demonstrated that Del-1 from dMSCs was involved in the pathogenesis of psoriasis through induced angiogenesis. And Del-1, αvβ3 and α5β1 may be potential new targets for inhibiting angiogenesis in psoriasis.

Background: Triple Negative Breast Cancer (TNBC) commonly displays Epidermal growth factor receptor (EGFR). Effective EGFR degradation results in the suppression of tumor in various models. Studies have addressed the relevance of this strategy in the treatment of TNBC. In the present study, we examined the effect of 17 β- estradiol on EGFR expression in MDA-MB-231 (TNBC) cell line and assessed whether 17 β-estradiol degrades EGFR by ubiquitination pathway. Objectives: The objective of this study is to treat MDA-MB-231 cell lines with Cycloheximide with or without 17β-estrdiol to observe whether 17β-estradiol leads to EGFR degradation and to treat with MG-132 to assess whether degradation occurs through ubiquitination pathway. Methods: MDA-MB-231 cells were treated with 17β-estradiol (E2) and EGFR expression was studied by western blotting at different intervals by using Cycloheximide chase. To assess ubiquitination pathway of degradation of EGFR in MDA-MB-231 cell line, MG-132 was used. Results: EGFR expression was reduced with β-estradiol treatment in MDA-MB-231 cell line with Cycloheximide chase. Upon Treatment with MG-132 and E2, EGFR expression did not reduce, suggesting that Estrogen degrades EGFR by ubiquitination pathway. Conclusion: Estrogen degrades EGFR in MDA-MB-231 cells and this degradation occurs by ubiquitination.

Background: Complement component 3 (C3) receptors play an important role as inflammatory mediators in the innate immune system, although their mechanisms were not well studied during constipation. Objective: The aim of this study is to investigate the regulatory role of C3 and its receptors' downstream signaling during constipation. Methods: Alterations in the C3, C3a receptor (C3aR), and C3b receptor (C3bR) expressions, PI3K/AKT pathway, RhoA/MLC pathway, MAP kinase pathway, and inflammatory cytokine expressions were measured in the mid colon of loperamide (Lop) treated SD rats. Results: Lop treatment successfully induced constipation phenotypes, including decreased stool parameters and histological structure alterations. The expression levels of C3 were significantly increased, whereas expressions of C3aR and C3bR were decreased during Lop-induced constipation. Moreover, significant upregulation was observed in the phosphorylation levels of PI3K, AKT, and GSK3β in mid colons of Lop treated SD rats. The expression of RhoA and phosphorylation of MLC were also enhanced in the Lop treated group. Furthermore, a similar pattern was detected in the MAP kinase pathway and inflammatory cytokine expressions. Subsequent to the Lop treatment, the phosphorylation of ERK and p38, as well as the mRNA levels of NF-ΚB, TNF-α, IL-6 and IL-1α were remarkably increased in the mid colon. Conclusion: These results indicate that Lop-induced constipation is tightly linked to the downregulation of C3aR and C3bR expressions, and upregulation of the C3 and C3Rs downstream signaling pathway, including PI3K/AKT, RhoA/MLC, and MAP kinase pathways as well as inflammatory cytokine expressions in the mid colon of SD rats.