Case Report: Analysis of Preserved Umbilical Cord Clarified X-Linked Anhidrotic Ectodermal Dysplasia With Immunodeficiency in Deceased, Undiagnosed Uncles

Family history is one key in diagnosing inborn errors of immunity (IEI); however, disease status is difficult to determine in deceased relatives. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is one of the hyper IgM syndromes that is caused by a hypomorphic variant in the nuclear factor kappa beta essential modulator. We identified a novel IKBKG variant in a 7-month-old boy with pneumococcal rib osteomyelitis and later found that his mother has incontinentia pigmenti. Genetic analysis of preserved umbilical cords revealed the same variant in two of his deceased maternal uncles. Analysis of preserved umbilical cord tissue from deceased relatives can provide important information for diagnosing IEI in their descendants.

The Mechanism Action of German Chamomile (Matricaria recutita L.) in the Treatment of Eczema: Based on Dose–Effect Weight Coefficient Network Pharmacology

To determine the active ingredients in German chamomile volatile oil and the mechanism of action in the treatment of eczema, this study used two parameters (ingredient content and oil–water partition coefficient) and established a new network pharmacology method based on the dose–effect weight coefficient. Through the new network pharmacology method, we found that German chamomile volatile oil regulated T-cell lymphatic subpopulations to inhibit the Th17 cell differentiation signaling pathway. This resulted in a reduction of interleukin 17 (IL-17), thereby inhibiting the activation of the nuclear factor kappa beta (NF-κB) and MAPK pathways, decreasing the secretion of the pro-inflammatory factors (tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6)), and reducing inflammation. In this study, a new dose–effect relationship synergistic network pharmacology method was established to provide a new method for the screening of effective ingredients and pathways of drugs, and to provide a basis for the follow-up studies of German chamomile volatile oil in the treatment of eczema.

Biochemical and molecular mechanisms associated with the effect of Phoenix dactylifera seeds on cyclophosphamide-induced hepato-renal toxicities in mice

Cyclophosphamide (CTX) causes severe side effects. Phoenix dactylifera L. showed biomedical values. This study aims to address the biochemical and molecular mechanisms of Phoenix dactylifera seeds extract (PDSE) effects on CTX-induced hepato-renal toxicities in mice. Forty male albino mice were divided into four groups: Gp 1 was served as a negative control, Gp2 was injected intraperitoneally (i.p) with PDSE (200 mg/kg) for 30 consecutive days. Gp3 was injected with CTX single dose (200 mg/kg) and Gp4 was injected with CTX then injected with PDSE. Hematological, biochemical, histopathological alterations, and gene expression for pro-inflammatory cytokine were assessed. GC-MS analysis showed the highest percentages of the peak areas were by Ethyl iso-allocholate, 1-Heptatriacotanol, and 9-12-15-Octadecatrienoic acid 2-3-dihydroxypropyl ester. Treatment with PDSE post-CTX-injection ameliorated the hematological, biochemical, and histological alterations by up-regulating the antioxidant biomarkers and downregulating tumor growth factor beta-1 (TGFβ-1), nuclear factor Kappa-beta (NFκ-β), cyclooxygenase-1 (COX-1) genes.

Plumbagin Enhances the Radiosensitivity of Tongue Squamous Cell Carcinoma Cells via Downregulating ATM

This study was designed to investigate whether plumbagin (PL) could sensitize ionizing radiation (IR) in tongue squamous cell carcinoma (TSCC) cells and its possible mechanisms. Cell proliferation and combination index analysis was based on MTT and colony formation assay. Flow cytometry was applied to analyze the cell cycle distribution and apoptosis after the treatment of PL and/or IR. RT-PCR was used to examine the gene expression level of ataxia telangiegatasiata muted (ATM) and nuclear factor kappa beta (NF- κB ) after various treatment groups. Western blot was used to examine the protein level of ATM and NF- κB as well as their phosphorylation level. PL enhances the cytotoxicity of IR in TSCC cells. Combination index was <1 which represents a synergistic effect. Combined PL and IR promoted G2/M arrest and apoptosis which could be reversed by ATM activator chloroquine phosphate. ATM and NF- κB were both inhibited by PL and IR combination. PL can efficiently enhance the radiosensitivity of TSCC cells by inducing G2/M arrest and apoptosis via downregulating ATM.

Borate reduces experimental supra-celiac aortic clamping-induced oxidative stress in lung and kidney, but fails to prevent organ damage

Background: This study aims to investigate the effects of 2-aminoethoxydiphenyl borate (2-APB) on aortic clamping-induced lung and kidney tissue oxidation, tissue inflammation, and histological damage in a rat model. Methods: A total of 28 adult female Wistar albino rats were randomly allocated to four equal groups: Control group, ischemia-reperfusion group, dimethyl sulfoxide group, and 2-APB group. Animals in the control group underwent median laparotomy. In the remaining groups, supra-celiac aorta was clamped for 45 min and, then, reperfusion was constituted for 60 min. The 2-APB (2 mg/kg) was administered before clamping. The remaining groups received saline (ischemia-reperfusion group) or dimethyl sulfoxide (dimethyl sulfoxide group). Kidney and lung tissue samples were harvested at the end of reperfusion. Results: Aortic occlusion caused increased tissue total oxidant status and reduced total antioxidant status and glutathione levels in the ischemia-reperfusion and dimethyl sulfoxide groups. Tissue interleukin-1 beta and tumor necrosis factor-alpha levels, nuclear factor kappa beta activation, and histological damage severity scores were also higher in these groups. The 2-APB treatment eliminated the increase in total oxidant status and the decrease in total antioxidant status and glutathione levels. It also caused a decrease in the interleukin-1 beta levels, although it did not significantly alter the tumor necrosis factor-alpha levels, nuclear factor kappa beta immunoreactivity, and histological damage scores. Conclusion: Borate exerted a beneficial antioxidant effect as evidenced by reduced oxidative stress; however, it did not inhibit nuclear factor kappa beta activation and prevent histological damage in supra-celiac aortic clamping-induced kidney and lung injury in rats.

Cellular and Molecular Response of Macrophages THP-1 during Co-Culture with Inactive Trichophyton rubrum Conidia

Trichophyton rubrum is causing an increasing number of invasive infections, especially in immunocompromised and diabetic patients. The fungal invasive infectious process is complex and has not yet been fully elucidated. Therefore, this study aimed to understand the cellular and molecular mechanisms during the interaction of macrophages and T. rubrum. For this purpose, we used a co-culture of previously germinated and heat-inactivated T. rubrum conidia placed in contact with human macrophages cell line THP-1 for 24 h. This interaction led to a higher level of release of interleukins IL-6, IL-2, nuclear factor kappa beta (NF-κB) and an increase in reactive oxygen species (ROS) production, demonstrating the cellular defense by macrophages against dead fungal elements. Cell viability assays showed that 70% of macrophages remained viable during co-culture. Human microRNA expression is involved in fungal infection and may modulate the immune response. Thus, the macrophage expression profile of microRNAs during co-culture revealed the modulation of 83 microRNAs, with repression of 33 microRNAs and induction of 50 microRNAs. These data were analyzed using bioinformatics analysis programs and the modulation of the expression of some microRNAs was validated by qRT-PCR. In silico analysis showed that the target genes of these microRNAs are related to the inflammatory response, oxidative stress, apoptosis, drug resistance, and cell proliferation.

S-Phase Kinase-Associated Protein-2 and Nuclear Factor-kappa Beta as Molecular Targets of Oral Burkitt’s Lymphoma Cell Induced by Quinolinone Derivate-Vesnarinone

Background: 3,4-Dihydro-6-[4-3,4-dimethoxybenzoyl-1-piperazinyl]-2(1H)-quinolinone (vesnarinone), a novel inotropic drug with unique and complex mechanisms of action, is known to show antitumor activity against several human malignancies. In the present study, vesnarinone-induced signal transduction of S-phase kinase-associated protein 2 (Skp2) and Nuclear Factor-kappa Beta (NF-κB) as molecular targets of oral malignant Burkitt’s lymphoma (Raji cells) was evaluated. Materials and Methods: Raji cells were incubated with vesnarinone at concentrations of 0, 1.25x10-2, 2.50x10-2, or 5.0x10-2 Molar. After 24 h, chemotactic cell migration was examined by a Boyden chamber kit. Apoptosis induction was observed by caspase-9 colorimetric assay. To evaluate levels of Skp2, NF-kB, and α-tubulin, Western blot analysis was performed. Results: Vesnarinone markedly suppressed chemotactic cell migration and significantly induced apoptosis by increasing the caspase-9 activity of Raji cells through down regulation of Skp2 and NF-κB. Conclusion: Vesnarinone decreased the expression of Skp2 and NF-κB indicating these molecules may be targeted for the treatment of oral malignant Burkitt’s lymphoma (BL). The results of this work offer a promising therapeutic approach for BL tumors.

Crude Radix Aconiti Lateralis Preparata (Fuzi) with Glycyrrhiza Reduces Inflammation and Ventricular Remodeling in Mice through the TLR4/NF-κB Pathway

Radix Aconiti Lateralis Preparata (Fuzi) is a traditional Chinese medicine. Its alkaloids are both cardiotonic and cardiotoxic; however, the underlying mechanisms are unclear. Compatibility testing and processing are the primary approaches used to reduce the toxicity of aconite preparations. The purpose of this study was to compare the effects of crude Fuzi (CFZ), CFZ combined with Glycyrrhiza (Gancao) (CFZ+GC), and prepared materials of CFZ (PFZ) on heart failure (HF) in C57BL/6J mice and explore the potential mechanisms of action of CFZ. Transverse aortic constriction (TAC) was used to generate the HF state, and CFZ (1.5 g·mL−1), PFZ (1.5 g·mL−1), or CFZ+GC (1.8 g·mL−1) was orally administered to the HF-induced mice daily. For the subsequent 8 weeks, hemodynamic indicators, ventricular pressure indices, and mass indices were evaluated, and histopathological imaging was performed. CFZ, CFZ+GC, and PFZ significantly improved left ventricular function and structure and reduced myocardial damage. CFZ+GC was more effective than CFZ and PFZ, whereas CFZ had higher toxicity than CFZ+GC and PFZ. CFZ and CFZ+GC attenuated ischemia-induced inflammatory responses and also inhibited Toll-like receptor-4 (TLR4) and nuclear factor kappa beta (NF-κB) action in the heart. Moreover, mass spectrometry analysis revealed a decrease in the levels of toxic components of CFZ+GC, whereas those of the protective components were increased. This study suggested that GC reduces the toxicity and increases the efficacy of CFZ on HF induced by TAC. Furthermore, GC+CFZ reduces the risk of HF by ameliorating the inflammation response, which might be partially related to the inhibition of the TLR4/NF-κB pathway.