A review on extracorporeal membrane oxygenation and kidney injury.

Extracorporeal membrane oxygenation (ECMO) is inevitable external life support in case of cardiac and respiratory failure since the 1970s. Acute kidney injury (AKI) and the requirement of renal replacement therapy (RRT) is a potential risk among these patients. This review aims to give an overview of the risk of AKI, RRT, and associated mortality among the patients who received ECMO for any of its indications. PubMed database was searched to find the relevant literature and the reference list of included studies was also searched for additional studies. The incidence of AKI ranged from 30% to 78% and RRT from 47% to 60% in ECMO patients. The pathophysiology of AKI in ECMO is multifactorial, and includes ischaemia, RBCs breakdown, comorbidity, conversion of zymogen form of pro-inflammatory mediators, structural alteration of the kidney, coadministration of nephrotoxic drugs, coagulation abnormality, and oxidative stress. ECMO was associated with the higher incidence of renal abnormalities, AKI, requirement of RRT, and associated mortality. Patients who underwent RRT had improved renal function and reduced overall mortality compared to the non-RRT group among the ECMO patients. Currently, there is no consensus evidence to support the superior use of the inline hemofilter system over continuous renal replacement therapy among patients who had AKI during ECMO.

CD4+ T cells apoptosis and conversion of Th1/Th2-type cytokines promote the progress of sporotrichosis.

Sporotrichosis is a fungal disease of the human and other mammals, caused by a complex of Sporothrix schenckii. The disease follows the traumatic inoculation to lead to fixed lesions, regional lymphangitic lesions, or even disseminated lesions including internal involvement, which depends on host immunological status and strain virulence. In this work, we observed the role of CD4+ T cells apoptosis and conversion of Th1/Th2-type cytokines in the cellular immunity regulation on mice model sporotrichosis. The experiments showed that there was more CD4+ T cells apoptosis, by endogenous apoptosis signaling pathway (P < .05), and more conversions of Th1/Th2-type cytokines in more severe and longer duration groups (P < .05). Meanwhile, the trends of the conversions of Th1/Th2-type cytokines were almost consistent with the CD4 + T cell's apoptosis in the corresponding groups. These findings suggest that CD4+ T cells apoptosis and conversion of Th1/Th2-type cytokines are contributing to promoting the progress of sporotrichosis.

Sepsis and Cerebral Dysfunction: BBB Damage, Neuroinflammation, Oxidative Stress, Apoptosis and Autophagy as Key Mediators and the Potential Therapeutic Approaches.

Sepsis-associated cerebral dysfunction is complex pathophysiology, generated from primary infections that are developed elsewhere in the body. The neonates, elderly population and chronically ill and long-term hospitalized patients are predominantly vulnerable to sepsis and related cerebral damage. Generally, electrophysiological recordings, severity and sedation scales, computerized imaging and spectroscopy techniques are used for its detection and diagnosis. About the underlying mechanisms, enhanced blood-brain barrier permeability and metalloprotease activity, tight junction protein loss and endothelial cell degeneration promote the influx of inflammatory and toxic mediators into the brain, triggering cerebrovascular damage. An altered neutrophil count and phenotype further dysregulate the normal neuroimmune responses and neuroendocrine stability via modulated activation of protein kinase C-delta, nuclear factor kappa-B and sphingolipid signaling. Glial activation, together with pro-inflammatory cytokines and chemokines and the Toll-like receptor, destabilize the immune system. Moreover, superoxides and hydroperoxides generate oxidative stress and perturb mitochondrial dynamics and ATP synthesis, propagating neuronal injury cycle. Activated mitochondrial apoptotic pathway, characterized by increased caspase-3 and caspase-9 cleavage and Bax/Bcl2 ratio in the hippocampal and cortical neurons, stimulate neurocognitive impairments. Additionally, altered LC3-II/I and P62/SQSTM1, p-mTOR, p-AMPK1 and p-ULK1 levels and dysregulated autophagosome-lysosome fusion decrease neuronal and glial energy homeostasis. The therapies and procedures for attenuating sepsis-induced brain damage include early resuscitation, cerebral blood flow autoregulation, implantable electric vagus nerve stimulation, antioxidants, statins, glucocorticoids, neuroimmune axis modulators and PKCδ inhibitors. The current review enumerates the pathophysiology of sepsis-induced brain damage, its diagnosis, the role of critical inducers and mediators and, ultimately, therapeutic measures attenuating cerebrovascular degeneration.

An alternative pathway for cellular protection in BRAF inhibitor resistance in aggressive melanoma type skin cancer.

Oncogenic alterations in the BRAF gene are identified in an estimate of 50% of melanomas and cause melanoma development. BRAF kinase inhibitors (BRAFi), including vemurafenib and dabrafenib, were discovered and used in the clinical treatment of BRAF-mutant metastatic melanoma. Though, BRAFi's therapeutic advantages are short term and short-lived associated with drug resistance. Although a few pathways of developed BRAFi resistance have also been established, in approximately 40% of melanomas, the cause for inherited resistance remains unclear. Recognizing a new process of developed BRAFi resistance might provide new possibilities to successfully treat BRAF mutant melanoma. In this study, we are exploring the compensatory alternative pathway followed by BRAFi/MEKi treated resistant cell for maintaining the long-term integrity and survival.

A secondary discoid lupus erythematosus induced by scald of edible oil: An illustration of Koebner phenomenon.

BACKGROUND: Discoid lupus erythematosus (DLE) is a most well-known clinical variation of chronic cutaneous lupus erythematosus inside the spectrum of lupus erythematosus (LE). Cutaneous trauma remains a significant and peculiar causative factor for DLE. AIMS: We present a case wherein the patient demonstrated unilateral distribution of DLE on a clinically normal appearing occult facial scald of edible oil, representing Koebner phenomenon (KP) i.e. occurrence of a new skin disease at the site of an unrelated and already healed one. PATIENT/METHODS: The 53 years old female patient was unique because she experienced DLE on the nasal back. RESULTS: The injury was totally settled following a month treatment of oral hydroxychloroquine and topical 0.03% tacrolimus ointment. After three months, she encountered an accidental edible oil scald on the right upper cheek. Several small vesicles appeared on a soybean-sized erythema base with a burning sensation. CONCLUSION: We review the literature and conclude by discussing important histologic highlights to think about while endeavoring to perceive the fundamental character and pathogenicity of such sores.

Role of Cellular Biomolecules in Screening, Diagnosis and Treatment of Colorectal Cancer.

BACKGROUND: Prevention is the primary strategy to avoid the occurrence and mortality of colorectal cancer. Generally, the concentrations of tumor markers tested during the diagnosis and believed to assist the detection of disease in the early stages of cancer. Some of the biomarkers are also important during treatment and real-time monitoring of the progress of treatment. METHODS: We considered a rationale search of key references from the database of peer-reviewed research and review literatures of colorectal cancer. The topic of search was focused on the novel methods and modern techniques of Screening, Diagnosis, and Treatment of colorectal cancer. The screened publications were critically analysed using a deductive content analysis and the matter was put in separate headings and sub headings. RESULTS: It was found that endoscopic examination, early detection, and surgery are some of the common strategies to manage colorectal cancer because late stages are difficult to treat due to the high-cost requirement and fewer chances of survival. As far as chemotherapy is concerned, systemic chemotherapy has been shown to offer the maximum benefit to patients with cancer metastasis. Among different chemotherapy measures, primary colorectal cancer prevention agents involve pharmaceuticals, phytochemicals, and dietary supplements are some of the standard options. CONCLUSION: In this review article, we have provided a comprehensive analysis of different biomarkers for the detection of colorectal cancer as well as different formulations developed for efficient treatment of the disease. The use of dietary supplements, the combinatorial approach, and nanotechnology-based strategies for colorectal cancer diagnosis and treatment are some of the recent and modern methods of cancer management.

Effect of FGF10 monoclonal antibody on psoriasis-like model in guinea pigs.

OBJECTIVE: To investigate the therapeutical effect of topical application of FGF10 monoclonal antibody on the guinea pig model with psoriasis. METHODS: Blank group, model group, hydrocortisone butyrate treatment group and high-dose (0.188 mg/ml), middle-dose (0.094 mg/ml) and low-dose (0.063 mg/ml) FGF10 antibody group were set, respectively. After two-week treatment, pathological changes of psoriasis-like models were observed by HE staining, and the difference in VEGF and PCNA expression levels among different groups was observed by immunohistochemical staining. RESULTS: All the test indicators of each treatment group were lower than those of the model group, and there was a significant difference (P<0.05). The inflammatory cell count of the high-dose FGF10 antibody group was not statistically different from those of the blank group (t=0.77, P=0.443), and the counts of the rest treatment groups were significantly higher than those of the blank group and the high-dose FGF10 antibody group (P<0.05). The epidermal thickness of each FGF10 antibody treatment group was significantly higher than that of hydrocortisone butyrate treatment group (P<0.05), while no statistical difference was found in the epidermal thickness among the FGF10 antibody treatment groups (P>0.05). FGF10 monoclonal antibodies can reduce the PCNA and VEGF expression in psoriasis-like model of guinea pig's ear. CONCLUSION: FGF10 monoclonal antibodies can affect keratinocyte proliferation and division and can also significantly inhibit the inflammatory response in the psoriasis model. Meanwhile, FGF10 monoclonal antibodies can produce a therapeutic effect on psoriatic lesions by inhibiting the abnormal epidermis cell proliferation and neovascularization of the dermis in the psoriasis model.

A case of cutaneous plasmacytosis.

The present study reports a case of cutaneous plasmacytosis in a 51-year-old patient suffering from infiltrated erythema of the right lower lateral femur for 4-5 years and perioral and abdominal erythema for 1 year. Histopathological examination showed that dense mature plasma cell-dominant inflammatory cell infiltration appeared in the deep dermis and between part of the subcutaneous tissues and that there were small numbers of lymphocytes and polykaryocytes. Immunopathogenetic analysis showed that the infiltrating plasma cells were positive for CD79a and CD138. The patient was diagnosed with cutaneous plasmacytosis.