-
Lemming Goldstein posted an update 4 days, 13 hours ago
001. Within the Roma/Gypsy population, we detected increased prevalence of the CVD-associated GG genotype. Increased prevalence of CVD among Roma/Gypsies subjects may be significantly linked to genetic background.Seven isolates from patients with American cutaneous leishmaniasis in the Amazon region of Brazil were phenotypically suggestive of Leishmania (Viannia) guyanensis/L. (V.) shawi hybrids. In this work, two molecular targets were employed to check the hybrid identity of the putative hybrids. Heat shock protein 70 (hsp70) gene sequences were analyzed by three different polymerase chain reaction (PCR) approaches, and two different patterns of inherited hsp70 alleles were found. Three isolates presented heterozygous L. (V.) guyanensis/L. (V.) shawi patterns, and four presented homozygous hsp70 patterns involving only L. (V.) shawi alleles. The amplicon sequences confirmed the RFLP patterns. The high-resolution melting method detected variant heterozygous and homozygous profiles. Single-nucleotide polymorphism genotyping/cleaved amplified polymorphic site analysis suggested a higher contribution from L. (V.) guyanensis in hsp70 heterozygous hybrids. Additionally, PCR-RFLP analysis targeting the enzyme mannose phosphate isomerase (mpi) gene indicated heterozygous and homozygous cleavage patterns for L. (V.) shawi and L. (V.) guyanensis, corroborating the hsp70 findings. In this communication, we present molecular findings based on partial informative regions of the coding sequences of hsp70 and mpi as markers confirming that some of the parasite strains from the Brazilian Amazon region are indeed hybrids between L. (V.) guyanensis and L. (V.) shawi.Autoimmune diseases are characterized by the loss of self-tolerance, leading to immune-mediated tissue destruction and chronic inflammation. PK11007 chemical structure Tyrosine kinase 2 (TYK2) protein plays a key role in immunity and apoptosis pathways. Studies have reported associations between single nucleotide polymorphisms (SNPs) in the TYK2 gene and autoimmune diseases; however, results are still inconclusive. Thus, we conducted a systematic review followed by meta-analysis. A literature search was performed to find studies that investigated associations between TYK2 SNPs and autoimmune diseases (multiple sclerosis, systemic lupus erythematosus, Crohn’s disease, ulcerative colitis, psoriasis, rheumatoid arthritis, type 1 diabetes, and inflammatory bowel disease). Pooled odds ratios (OR) with 95 % CI were calculated using random (REM) or fixed (FEM) effects models in the Stata 11.0 Software. Thirty-four articles were eligible for inclusion in the meta-analyses, comprising 9 different SNPs rs280496, rs280500, rs280523, rs280519, rs2304256, rs12720270, rs12720356, rs34536443, and rs35018800. Meta-analysis results showed the minor alleles of rs2304256, rs12720270, rs12720356, rs34536443, and rs35018800 SNPs were associated with protection against autoimmune diseases. Moreover, the A allele of the rs280519 SNP was associated with risk for systemic lupus erythematosus. Our meta-analyses demonstrated that the rs2304256, rs12720270, rs12720356, rs34536443, rs35018800, and rs280519 SNPs in the TYK2 gene are associated with different autoimmune diseases.The deformability of red blood cells is an essential parameter that controls the rheology of blood as well as its circulation in the body. Characterizing the rigidity of the cells and their heterogeneity in a blood sample is thus a key point in the understanding of occlusive phenomena, particularly in the case of erythrocytic diseases in which healthy cells coexist with pathological cells. However, measuring intracellular rheology in small biological compartments requires the development of specific techniques. We propose a technique based on molecular rotors – viscosity-sensitive fluorescent probes – to evaluate the above key point. DASPI molecular rotor has been identified with spectral fluorescence properties decoupled from those of hemoglobin, the main component of the cytosol. After validation of the rotor as a viscosity probe in model fluids, we showed by confocal microscopy that, in addition to binding to the membrane, the rotor penetrates spontaneously and uniformly into red blood cells. Experiments on red blood cells whose rigidity is varied with temperature, show that molecular rotors can detect variations in their overall rigidity. A simple model allowed us to separate the contribution of the cytosol from that of the membrane, allowing a qualitative determination of the variation of cytosol viscosity with temperature, consistent with independent measurements of the viscosity of hemoglobin solutions. Our experiments show that the rotor can be used to study the intracellular rheology of red blood cells at the cellular level, as well as the heterogeneity of this stiffness in a blood sample. This opens up new possibilities for biomedical applications, diagnosis and disease monitoring.Keratinocyte growth factor-2 (KGF-2) can regulate the proliferation and differentiation of keratinocyte, which plays a remarkable role in maintaining normal tissue structure and promoting wound healing. As an effective strategy, KGF-2 solution is widely used in the treatment of wounds in clinical applications. However, KGF-2 in solution cannot achieve sustained release, which results in drug loss and unnecessary waste. Polysaccharide hemostasis microspheres (PHMs) are an ideal drug loading platform due to their special “lotus seedpod surface-like” morphology and structure. Herein, to realize the controllable release of KGF-2, PHMs loaded with KGF-2 (KGF-2@PHMs) were prepared. It was found that the bioavailability of KGF-2 was improved greatly. Most importantly, KGF-2@PHMs can reduce inflammation and accelerate the wound healing process due to the controlled release of KGF-2. KGF-2@PHMs might be a potential alternative strategy for wound healing in future clinical applications.A novel hybrid drug carrier has been designed, taking N-doped mesoporous carbon (NMCS) as the core and PEG-PEI as the outer shell. NMCS was functionalized with a photocleavable nitrobenzyl-based linker following a click reaction. Gemcitabine was loaded into NMCS prior to the functionalization via π-π stacking interactions. NIR and the pH-responsive behavior of NMCS-linker-PEG-PEI bestow the multifunctional drug carrier with the controlled release of gemcitabine triggered by dual stimuli. The NMCS core upconverts NIR light to UV, which is absorbed by a photosensitive molecular gate and results in its cleavage and drug release. Further, NMCS converts NIR to heat, which deforms the outside polymer shell, thus triggering the drug release process. The release can be promptly arrested if the NIR source is switched off. A promising gemcitabine release of 75% has been achieved within 24 h under the dual stimuli of pH and temperature. NMCS-linker-PEG-PEI produced reactive oxygen species (ROS), which were verified in FaDu cells using flow cytometry.