Suppression of TLR4/MyD88/TAK1/NF-κB/COX-2 Signaling Pathway in the Central Nervous System by Bexarotene,a Selective RXR Agonist,Prevents Hyperalgesia in the Lipopolysaccharide-Induced Pain Mouse Model

Neurochemical Research - A selective RXR agonist, bexarotene, has been shown to have anti-inflammatory, anti-nociceptive, and neuroprotective effects in several models of numerous neurological...     

Comparison of outpatient and inpatient spa therapy in knee osteoarthritis

Osteoarthritis (OA) is a common condition that impacts many people worldwide and involves weight-bearing joints, resulting in chronic pain. In this study, we aimed to compare the effectiveness of inpatient and outpatient physical therapy modalities and spa combination treatments on pain and functional status in patients with knee osteoarthritis. Seventy-four patients diagnosed with primary knee osteoarthritis were included in this study. The patients were randomized into two groups, inpatient (n?=?37) and outpatient (n?=?37) physical therapy. All patients received a physical therapy program (superficial heater + deep heater + transcutaneous electrical nerve stimulation) for 2 weeks and spa therapy. All cases were evaluated clinically, laboratory, and radiographically. In order to evaluate pain and functional status, the Visual Analogue Scale (VAS), Western Ontario and McMaster Universities osteoarthritis index (WOMAC), and Timed Up and Go (TUG) test were used before and after treatment. There was no significant difference between the two groups in the TUG test and WOMAC scores (p?>?0.05). However, a significant difference was found in VAS scores in favor of the outpatient group (p?<?0.05). As a result, although there was a significant improvement in pain scores in the outpatient group, multicenter studies with larger patient groups may provide more evidence.

     

The effects of desert dust storms,air pollution,and temperature on morbidity due to spontaneous abortions and toxemia of pregnancy: 5-year analysis

International Journal of Biometeorology - Epidemiological studies have suggested an association between particulate air pollution, increased temperatures, and morbidity related to pregnancy...     

Chitosan and silver nanoparticles are attractive auxin carriers: A comparative study on the adventitious rooting of microcuttings in apple rootstocks

Nanocarriers for encapsulation and sustained release of agrochemicals such as auxins have emerged as an attractive strategy to provide enhanced bioavailability and efficacy for improved crop yields and nutrition quality. Here, a comparative study was conducted on the effectiveness of chitosan-as a biopolymeric nanocarrier- and silver-as a metallic nanocarrier- on in vitro adventitious rooting potential of microcuttings in apple rootstocks, for the first time. Auxins indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) loaded silver (nAg) or chitosan nanoparticles (nChi) were synthesized. Scanning electron microscopy and transmission electron microscopy studies showed the spherical shape of the nanoparticles. The average particle size of IAA-nChi was 167.5 ± 0.1 nm while that of IBA-nChi was 123.2 ± 2.6 nm. The hydrodynamic diameter of the nAg-IAA and nAg-IBA particles were measured as 93.66 ± 5 nm and 71.41 ± 3 nm, respectively. Fourier transform infrared spectroscopy analyses confirmed the encapsulation of IAA or IBA in the chitosan nanoparticles. Meanwhile, the characteristic peaks of IAA or IBA were detected on silver nanoparticles. In-vitro adventitious rooting of microcuttings of Malling Merton 106 (MM 106) was significantly higher both in chitosan and silver nanoparticles loaded with IAA or IBA (91.7%–62.5%) compared to free IAA or IBA applications (50.0%–33.3%), except for 2.0 mg L^–1 IBA (66.7%). However, the application of 2 mg L^–1 IBA and IBA-nChi at all concentrations caused an undesirable large callus development.     

In vitro induction of neoantigen-specific T cells in myelodysplastic syndrome,a disease with low mutational burden

Therapies that utilize immune checkpoint inhibition work by leveraging mutation-derived neoantigens and have shown greater clinical efficacy in tumors with higher mutational burden. Whether tumors with a low mutational burden are susceptible to neoantigen-targeted therapy has not been fully addressed. To examine the feasibility of neoantigen-specific adoptive T-cell therapy, the authors studied the T-cell response against somatic variants in five patients with myelodysplastic syndrome (MDS), a malignancy with a very low tumor mutational burden. DNA and RNA from tumor (CD34⁺) and normal (CD3⁺) cells isolated from the patients’ blood were sequenced to predict patient-specific MDS neopeptides. Neopeptides representing the somatic variants were used to induce and expand autologous T cells ex vivo, and these were systematically tested in killing assays to determine the proportion of neopeptides yielding neoantigen-specific T cells. The authors identified a total of 32 somatic variants (four to eight per patient) and found that 21 (66%) induced a peptide-specific T-cell response and 19 (59%) induced a T-cell response capable of killing autologous tumor cells. Of the 32 somatic variants, 11 (34%) induced a CD4⁺ response and 11 (34%) induced a CD8⁺ response that killed the tumor. These results indicate that in vitro induction of neoantigen-specific T cells is feasible for tumors with very low mutational burden and that this approach warrants investigation as a therapeutic option for such patients.     

Protective Effect of Nigella sativa and Nigella damascena Fixed Oils Against Aflatoxin Induced Mutagenicity in the Classical and Modified Ames Test

The antioxidant and mutagenic/antimutagenic activities of the fixed oils from Nigella sativa (NSO) and Nigella damascena (NDO) seeds, obtained by cold press-extraction from the cultivar samples, were comparatively investigated for the first time. The antimutagenicity test was carried out using classical and modified Ames tests. The fatty acid composition of the fixed oils was characterized by gas chromatography–mass spectrometry (GC-MS) while the quantification of thymoquinone in the fixed oils was determined by UPC². The main components of the NSO and NDO were found to be linoleic acid, oleic acid, and palmitic acid. The results of the Ames test confirmed the safety of NSO and NDO from the viewpoint of mutagenicity. The results of the three antioxidant test methods were correlated with each other, indicating NDO as having a superior antioxidant activity, when compared to the NSO. Both NSO and NDO exhibited a significant protective effect against the mutagenicity induced by aflatoxin B1 in Salmonella typhimurium TA98 and TA100 strains. When microsomal metabolism was terminated after metabolic activation of the mycotoxin, a significant increase in antimutagenic activity was observed, suggesting that the degradation of aflatoxin B1 epoxides by these oils may be a possible antimutagenic mechanism. It is worthy to note that this is the first study to assess the mutagenicity of NSO and NDO according to the OECD 471 guideline and to investigate antimutagenicity of NDO in comparison to NSO against aflatoxin.     

A review of the genus Rusa in the indo-malayan archipelago and conservation efforts

Genus Rusa, belonging to the deer family Cervidae is native to the Indo-Malaya Archipelago (IMA). However, detailed information on the Rusa genus in the IMA is limited. This review provides comprehensive information on the Rusa genus in the IMA including, threats and conservation efforts. There are four species of deer in Rusa genus, which is Sambar deer (Rusa unicolor), Javan deer (Rusa timorensis), Visayan spotted deer (Rusa alfredi) and Philippine deer (Rusa marianna). Despite their wide distribution in the South Asian and Southeast Asian regions, they are under serious threats. Some conservation efforts that are being done to protect and conserve them among others are; (1) facilities protection, (2) habitat enrichment programme, (3) Ex-situ conservation, (4) legislations, and (5) captive breeding. Conservation through genetics is also an important step in conserving these species. Recommendations for conservation of the genus are also discussed; 1. maintenance of ecosystem. 2. more effective monitoring system on the existing protected area. 3. ex-situ conservation, and 4. habitat monitoring.     

Clinical and pathological significance of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) expression in high grade serous ovarian cancer

We investigated programmed cell death 1 (PD-1) / programmed cell death ligand 1 (PD-L1) expression in high grade serous ovarian cancer (HGSOC) and its relationship to tumor infiltrating lymphocytes (TIL) and prognosis. Formalin fixed paraffin embedded (FFPE) samples of 94 HGSOC cases were included in the study. Immunohistochemical analysis (CD3, CD4, CD8, PD-1 and PD-L1) was performed. Samples were analyzed for expression of immune proteins in the peritumoral stromal and intratumoral areas, scored, and expression was correlated with overall survival, stage, and age. PD-L1 staining ratio with a score greater than 0 was found to have lower survival. There were two positive staining patterns, patchy/diffuse and patchy/focal patterns, in 24 (25.5%) cases. Considering the threshold value ≥5%, we demonstrated that the PD-L1 positive cancer cell membrane immunoreactivity rate and patchy/diffuse PD-L1 expression were 9.6% (n = 9). There was statistically significant relationship between high PD-1 scores and PD-L1 cases of ≥ 5%. A statistically significant difference was found between PD-L1 staining and survival in patients with a threshold ≥ 5%. However an appropriate rate for treatment was determined in 9.6% cases. There was a statistically significant correlation between PD-1 positive TIL score and intratumoral CD3, peritumoral stromal CD3, intratumoral CD4 and intratumoral CD8 positive cells. Survival was lower in cases with higher PD-L1 positive stromal TIL score.     

The relation of oxidative stress and apoptosis to histopathologic alterations in the lungs as a result of global cerebral ischemia

ABSTRACT

Heart attack and oxygen deficiency may cause necrosis in the brain and other tissues. We investigated the histopathological effects of nitric oxide (NO) on ischemia/reperfusion in lung and hippocampus using a rat brain bilateral occlusion ischemia model. Male rats were assigned to sham (SH), ischemic preconditioning (PC), global ischemia (GI) and ischemic reperfusion (IR) groups. Before ischemia was induced, blood was drawn to induce hypovolemic hypotension and for blood gas testing. After sacrifice, samples of hippocampus were harvested. Sections were examined using hematoxylin and eosin (H & E) staining and immunostaining using primary antibodies for GFAP, S100β, iNOS, eNOS and the TUNEL method. Following ischemia, we found evidence of gliosis induced oxidative stress and apoptosis in the hippocampus. No significant differences were detected between the SH and PC groups. In the GI and IR groups, apoptosis and necrosis were observed in the hippocampus. Lung sections were stained with H & E and Masson’s trichrome (MT) and immunostained for iNOS and eNOS. The TUNEL method was used to detect apoptosis. Interstitial edema, vascular congestion, intra-alveolar hemorrhage, perivascular edema, neutrophil infiltration and disruption of alveoli were observed after global ischemia and ischemic reperfusion. Inflammatory cells were detected in the connective tissue. The IR and GI groups exhibited significantly more apoptotic cells than the SH or PC groups. Free radicals, such as nitric oxide (NO), that appear following ischemia and reperfusion in the brain may also injure the lungs. Increased NO in both lung and brain tissue suggests that apoptosis in these organs can be induced by reactive nitrogen species.