Angiotensin-Converting Enzyme 2 (ACE2) Gene Polymorphism in Patients with Type 2 Diabetes (T2DM) in Thi-Qar, Iraq.

The increased levels of blood glucose associated with genetic and/or environmental risk factors have been known as Type 2 diabetes mellitus (T2D). T2D is categorized as a dangerous clinical syndrome for global public health. It has been well-documented that several candidate genes are functionally associated with T2D. One of the candidate genes linked to T2D is named Angiotensin-converting enzyme 2 (ACE2). Therefore, this study aimed to evaluate the relationship between ACE2 gene polymorphism and the development of T2D in Iraq. This study includes 150 participants (100) T2D patients and 50 healthy participants as a control group. Through the analysis of the recorded data, 78% were nonsmokers, while the rest were smokers. The current study found 61% of T2D patients suffer from hypertension (P-value=0.028). In this study, 80% of patients have the GG genotype. However, 26% have the GA genotype without a significant difference between patients and the control group (OR=0.78). Mutations in the ACE2 gene were recorded in the gene bank with accession numbers LC656363, LC656364, LC656365, LC656366, LC656367 and LC656368. The current study showed a relationship between mutations and polymorphisms in the ACE2 gene and type 2 diabetes mellitus. The polymorphisms, deletion and insertion mutations had an important role in the pathophysiology of type 2 diabetes mellitus. The study recorded some mutations in the Clinical Variation website at NCBI's National Center for Biotechnology Information. The current study showed a relationship between smoking and the risk of developing type 2 diabetes. The current study's findings indicated that mutations affecting the three encoded genes could directly cause impaired insulin production in people with type 2 diabetes.

Xeroderma Pigmentosum C: A Valuable Tool to Decipher the Signaling Pathways in Skin Cancers.

Xeroderma pigmentosum (XP) is a rare autosomal genodermatosis that manifests clinically with pronounced sensitivity to ultraviolet (UV) radiation and the high probability of the occurrence of different skin cancer types in XP patients. XP is mainly caused by mutations in XP-genes that are involved in the nucleotide excision repair (NER) pathway that functions in the removal of bulky DNA adducts. Besides, the aggregation of DNA lesions is a life-threatening event that might be a key for developing various mutations facilitating cancer appearance. One of the key players of NER is XPC that senses helical distortions found in damaged DNA. The majority of XPC gene mutations are nonsense, and some are missense leading either to the loss of XPC protein or to the expression of a truncated nonfunctional version. Given that no cure is yet available, XPC patients should be completely protected and isolated from all types of UV radiations (UVR). Although it is still poorly understood, the characterization of the proteomic signature of an XPC mutant is essential to identify mediators that could be targeted to prevent cancer development in XPC patients. Unraveling this proteomic signature is fundamental to decipher the signaling pathways affected by the loss of XPC expression following exposure to UVB radiation. In this review, we will focus on the signaling pathways disrupted in skin cancer, pathways modulating NER's function, including XPC, to disclose signaling pathways associated with XPC loss and skin cancer occurrence.

Signaling Pathways, Chemical and Biological Modulators of Nucleotide Excision Repair: The Faithful Shield against UV Genotoxicity.

The continuous exposure of the human body's cells to radiation and genotoxic stresses leads to the accumulation of DNA lesions. Fortunately, our body has several effective repair mechanisms, among which is nucleotide excision repair (NER), to counteract these lesions. NER includes both global genome repair (GG-NER) and transcription-coupled repair (TC-NER). Deficiencies in the NER pathway underlie the development of several DNA repair diseases, such as xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). Deficiencies in GG-NER and TC-NER render individuals to become prone to cancer and neurological disorders, respectively. Therefore, NER regulation is of interest in fine-tuning these risks. Distinct signaling cascades including the NFE2L2 (NRF2), AHR, PI3K/AKT1, MAPK, and CSNK2A1 pathways can modulate NER function. In addition, several chemical and biological compounds have proven success in regulating NER's activity. These modulators, particularly the positive ones, could therefore provide potential treatments for genetic DNA repair-based diseases. Negative modulators, nonetheless, can help sensitize cells to killing by genotoxic chemicals. In this review, we will summarize and discuss the major upstream signaling pathways and molecules that could modulate the NER's activity.