Highlights • Diabetic tissues are exposed to highly reactive chemical species over months to years. • Diffusion, autooxidation, reaction with superoxide control the fate of NO. • NO , nitrous ...anhydride, and nitrogen dioxide radicals generate protein and DNA damage. • Alteration in energy metabolism, sorbitol pathway, inflammatory mediators regulate ROS. • Serum thiols are important peroxides scavengers that protect the surrounding tissues.
There has been less volume of literature focusing on the Immune-related Hematological Adverse Drug Events (Hem-irAEs) of Immune Checkpoint Inhibitors (ICPis) in cancer patients. Furthermore, there ...has been no consensus about the management of hematological toxicity from immunotherapy in the recently published practice guidelines by the European Society for Medical Oncology (ESMO). We conducted a systematic review of case reports/series to describe the diagnosis and management of potentially rare and unrecognized Hem-irAEs. We searched Medline, OVID, Web of Science for eligible articles. Data were extracted on patient characteristics, Hem-irAEs, and management strategies. We performed quality assessment using the Pierson-5 evaluation scheme and causality assessment using the Naranjo scale. Our search retrieved 49 articles that described 118 cases. The majority of patients had melanoma (57.6%) and lung cancer (26.3%). The most common Hem-irAEs reported with ICPis (such as nivolumab, ipilimumab, and pembrolizumab) were thrombocytopenia, hemolytic and aplastic anemias. Less reported adverse events included agranulocytosis and neutropenia. Steroids were commonly used to treat these adverse events with frequent success. Other used strategies included intravenous immunoglobulins (IVIG), rituximab, and transfusion of blood components. The findings of this review provide more insights into the diagnosis and management of the rarely reported Hem-irAEs of ICPis.
Neonatal pulmonary hypertension (PHN) is a lethal progressive disease that occurs in prenatal circulatory transition. Mechanical wall strain caused by cardiac pulsation integrates with hypoxia to ...generate rapidly progressive myocyte cytoskeleton disassembly and failure to exert force generation. The physiological responses to such an interaction have not been investigated. The persistent phenotype does not respond to traditional vasodilator therapy; hence, there is a need for new treatment strategies to improve the morbidity and mortality outcomes. We reviewed the current research methods, models, and markers of persistent PHN relevant to oxidative and nitrosative stress as well as cell fate commitment, with an emphasis on apoptosis and proliferation. We surveyed potential investigations into the role of senescence in neonatal PHN cell fate decision programming during vasodilator treatment and suggested putative drug targets to improve clinical outcomes. We identified important signaling intermediates of senescence and cell cycle entry regulation in hypertensive pulmonary arterial tissues.
Identifying the concerted interplay between ROS/RNS generation, senescence, and inflammatory signaling will lead to therapeutic targets to combat vascular remodeling in PHN; the factor most limiting to treatment responses is irreversible fibrotic thickening. Prevention of the latter will help reduce mortality and morbidity in infants with PHN and prolong the window of opportunity for vasodilator therapies.
Wound healing comprises organized events involving tissue repair and regeneration. The discovery of toll-like receptors (TLRs) sheds recent light on the mechanisms involved in initiating inflammatory ...responses throughout the healing cascades. Hibiscus sabdariffa (HS) components may exhibit a wound healing action, owing to their antioxidant and anti-inflammatory activities. This study was designed to investigate the early effects of HS loaded in an ointment base on wound healing, antioxidant, antimicrobial effects, burning intensity, and histopathological features on the rat burn model in comparison to the standard treatment, Iruxol® ointment. A burn injury model was used to evaluate the wound healing potency of the preparation. Rats were treated with ointments three times on the day of the induction of the burn. Findings revealed that the strong antioxidant properties of the HS-loaded ointment augmented the skin healing potential by stimulating biomarkers required for skin regeneration. HS repressed the burning-induced inflammation by the effective reduction in the levels of tumor necrosis factor α (TNF-α) and IL-6 through TLR4 protein inhibition. Topical HS downregulates transforming growth factor-beta (TGF-β) levels. HS extract possesses a potential bactericidal activity against highly resistant clinical isolates of Pseudomonas aeruginosa. Overall, this study proclaims that HS-loaded topical preparations could be a valuable product that serves as adjuvants to accelerate burn wound healing through inactivating the TLR4 pathway.
Diabetes mellitus is a metabolic disorder that is characterized by impaired glucose tolerance resulting from defects in insulin secretion, insulin action, or both. Epigenetic modifications, which are ...defined as inherited changes in gene expression that occur without changes in gene sequence, are involved in the etiology of diabetes.
In this review, we focused on the role of DNA methylation and protein misfolding and their contribution to the development of both type 1 and type 2 diabetes mellitus.
Changes in DNA methylation in particular are highly associated with the development of diabetes. Protein function is dependent on their proper folding in the endoplasmic reticulum. Defective protein folding and consequently their functions have also been reported to play a role. Early treatment of diabetes has proven to be of great benefit, as even transient hyperglycemia may lead to pathological effects and complications later on. This has been explained by the theory of the development of a metabolic memory in diabetes. The basis for this metabolic memory was attributed to oxidative stress, chronic inflammation, non-enzymatic glycation of proteins and importantly, epigenetic changes. This highlights the importance of linking new therapeutics targeting epigenetic mechanisms with traditional antidiabetic drugs.
Although new data is evolving on the relation between DNA methylation, protein misfolding, and the etiology of diabetes, more studies are required for developing new relevant diagnostics and therapeutics.
There is neither a unifying concept nor a sufficient multivariable approach to apply the use of laboratory markers to clinical practice with respect to the metabolic syndrome. The relationship of ...metabolic syndrome to the development of hypertension and the concurrent development of chronic renal disease has become evident. We have shown biomarkers to have significant value in combination for assessing heart failure and pulmonary hypertension. The pathogenesis of hypertension and cardiovascular and renal diseases is tightly linked to increased oxidative stress and reduced nitric oxide bioavailability. This review addresses the mathematical foundation for such an evaluation of the biological markers and the computational tools and the interest in outcomes research for improved healthcare practice. The review also addresses the heavy investment in health information systems intended to improve a rapidly consolidating patient health network. This has become important to enable a suitable method of assessing drug efficacy and of lifestyle changes to improve the population health, the pharmaceutical industry, and allied health sciences.
Background
Invasive colonoscopy is the gold standard for patients at risk for colorectal cancer. However, the need for non-invasive and specific markers is required.
Objective
To evaluate the ...sensitivity of the glycolytic pyruvate kinase isoenzyme type M2 dimer (M2PK) as a diagnostic biomarker for colorectal cancer (CRC) and adenomatous colorectal polyps (CRP) screening.
Design
Case-control.
Patients
Twenty patients with CRC, 20 patients with CRP (lack criteria for colonic cancer by biopsy), and 20 normal subjects.
Outcome
Complete blood count (CBC), erythrocyte sedimentation rate (ESR), tumor markers: carcino embryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), fecal occult blood test (FOBT), and fecal M2PK. Pelvic and abdominal ultrasound (US), colonoscopy, and a histopathological examination.
Results
Only weight loss and cachexia were significantly associated with CRC than CRP or control groups. M2PK was the most sensitive and specific test in differentiating CRC from CRP and the control subjects (sensitivity = 75%, specificity = 100%).
Limitations
(1) The selection of cases for three well-matched groups, as to perform colonoscopy in well-prepared cases and conditions. (2) Replicates in more than 20 cases for confirmation at the expense of enrolling new patients. (3) The cost associated with tumor markers analysis.
Conclusion
Fecal M2PK can be used as a precolonoscopy screening test for CRC patients, and is superior to other tumor markers, and in indicating the progress of colorectal adenomas > 1 cm. Thus being cost-effective and easy-to-perform test, it is a feasible tool to preselect patients who require colonoscopy.
Diabetes Mellitus (DM) is a multisystemic disease involving the homeostasis of insulin secretion by the pancreatic islet beta cells (β-cells). It is associated with hypertension, renal disease, and ...arterial and arteriolar vascular diseases.
The classification of diabetes is identified as type 1 (gene linked β-cell destruction in childhood) and type 2 (late onset associated with β-cell overload and insulin resistance in peripheral tissues. Type 1 diabetes is characterized by insulin deficiency, type 2 diabetes by both insulin deficiency and insulin resistance. The former is a genetically programmed loss of insulin secretion whereas the latter constitutes a disruption of the homeostatic relationship between the opposing activity of β- cell insulin and alpha cell (α-cell) glucagon of the Islets of Langerhans. The condition could also occur in pregnancy, as a prenatal occurring event, possibly triggered by the hormonal changes of pregnancy combined with β-cell overload. This review discusses the molecular basis of the biomolecular changes that occur with respect to glucose homeostasis and related diseases in DM. The underlying link between pancreatic, renal, and microvascular diseases in DM is based on oxidative stress and the Unfolded Protein Response (UPR).
Studying proteome changes in diabetes can deepen our understanding of the biomolecular basis of disease and help us acquire more efficient therapies.
PDF
