In vitro antileishmanial potentialities of essential oils from Citrus limon and Pistacia lentiscus harvested in Tunisia

xlomafota.13 shared this article with you from Inoreader In vitro antileishmanial potentialities of essential oils from Citrus limon and Pistacia lentiscus harvested in Tunisia Via Latest Results for Parasitology Research Abstract Leishmaniasis is a tropical parasitic disease that affects up to 12 million people worldwide. Current chemotherapies have limitations such as toxicity, high cost, and parasite resistance. This work aims to select an essential oil (EssOil) isolated from the Tunisian flora as a new antileishmanial candidate. Two plants were chosen for their antileishmanial potential: Citrus limon (Citrus) and Pistacia lentiscus (Pistacia). Each of these plants was harvested from two different sites (area 1 and area 2). Extracted EssOils were characterized using GC-MS. Their antiparasitic activity against axenic and intracellular Leishmania major amastigotes and their cytotoxicity were assessed. Citrus EssOil from area 1 displayed an interesting activity against L. major intramacrophage amastigotes with IC50 value at 4.2 ± 1.3 μg/mL. Interestingly, this activity was close to that of miltefosine. Mod erate activities against intracellular amastigote were observed for Pistacia EssOil from area 1 and Citrus EssOil from area 2. However, low cytotoxicity with high selectivity index was proved only for Citrus EssOil from area 1, revealing its safety for macrophages. This study also demonstrated for the first time the antileishmanial activity of EssOil extracted from Citrus limon leaves. The EssOil interesting activity could be related to the lipophilic properties of terpenes that were shown in literature to contribute to the disruption of parasite intracellular metabolic pathways. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Attenuation of the Induction of TLRs 2 and 4 Mitigates Inflammation and Promotes Neurological Recovery After Focal Cerebral Ischemia

xlomafota.13 shared this article with you from Inoreader Attenuation of the Induction of TLRs 2 and 4 Mitigates Inflammation and Promotes Neurological Recovery After Focal Cerebral Ischemia Via Latest Results for Translational Stroke Research Abstract The intense inflammatory response triggered in the brain after focal cerebral ischemia is detrimental. Recently, we showed that the suppression of toll-like receptors (TLRs) 2 and 4 attenuates infarct size and reduces the expression of pro-inflammatory cytokines in the ischemic brain. In this study, we further examined the effect of unsuppressed induction of TLRs 2 and 4 on the expression of its downstream signaling molecules and pro-inflammatory cytokines 1 week after reperfusion. The primary purpose of this study was to investigate the effect of simultaneous knockdown of TLRs 2 and 4 on M1/M2 microglial polarization dynamics and post-stroke neurological deficits and the recovery. Transient focal cerebral ischemia was induced in young adult male Sprague-Dawley rats by the middle cerebral artery occlusion (MCAO) procedure using a monofilament suture. Appropriate cohorts of rats were treated with a nanoparticle formulation of TLR2shRNA and TLR4shRNA (T2sh+T4s h) expressing plasmids (1 mg/kg each of T2sh and T4sh) or scrambled sequence inserted vector (vehicle control) expressing plasmids (2 mg/kg) intravenously via tail vein immediately after reperfusion. Animals from various cohorts were euthanized during reperfusion, and the ischemic brain tissue was isolated and utilized for PCR followed by agarose gel electrophoresis, real-time PCR, immunoblot, and immunofluorescence analysis. Appropriate groups were subjected to a battery of standard neurological tests at regular intervals until 14 days after reperfusion. The increased expression of both TLRs 2 and 4 and their downstream signaling molecules including the pro-inflammatory cytokines was observed even at 1-week after reperfusion. T2sh+T4sh treatment immediately after reperfusion attenuated the post-ischemic inflammation, preserved the motor function, and promoted recovery of the sensory and motor functions. We conclude that the post-ischemic induction of TLRs 2 and 4 per sists for at least 7 days after reperfusion, contributes to the severity of acute inflammation, and impedes neurological recovery. Unlike previous studies in TLRs 2 or 4 knockout models, results of this study in a pharmacologically relevant preclinical rodent stroke model have translational significance. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Impact of elevated core temperature on cognition in hot environments

xlomafota.13 shared this article with you from Inoreader Impact of elevated core temperature on cognition in hot environments within a military context Via Latest Results for European Journal of Applied Physiology Abstract Purpose Cognition can be impaired during exercise in the heat, potentially contributing to military casualties. To our knowledge, the independent role of elevated core temperature during exercise has not been determined. The aim of the current study was to evaluate effects of elevated core temperature on cognition during physically encumbering, heated exercise, and to determine whether the perceptual cooling effects of menthol preserves cognition. Methods Eight participants complete three trials in randomised order: one normothermic (CON) and two with elevated (38.5°C) core temperature, induced by prior immersion in neutral versus hot water The CON trial and one hot trial (HOT) used a water mouth-rinse following each cognitive task of the trial, (HOT) while the other used a menthol mouth-rinse (MENT). Participants walked in humid heat (33°C, 75% relative humidity) in military clothing, completing a cognitive battery of reaction time, perceptual processing, working memory, executive function, cognitive flexibility, vigilance, and declarative memory. Results No differences in cognitive performance were observed between any conditions. Near-infrared spectroscopy showed greater oxygenated haemoglobin tissue content in HOT and MENT compared to CON (ΔO2Hb-deO2Hb: 2.3 ± 4.5 µM, p < .024), and lower deoxygenated haemoglobin in MENT than in CON or HOT (p = .017), suggesting higher brain metabolism during the more stressful conditions. Conclusion Moderately elevated core (38.5°C) and skin temperature does not appear to impair cognitive performance during exercise despite mildly elevated cerebral metabolism. The effects of menthol remain undetermined due to the lack of heat-mediated cognitive impairment. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hypoxic re-exposure retains hematological but not performance adaptations post-altitude training

xlomafota.13 shared this article with you from Inoreader Hypoxic re-exposure retains hematological but not performance adaptations post-altitude training Via Latest Results for European Journal of Applied Physiology Abstract Purpose To test the hypothesis that hypoxic re-exposure after return from natural altitude training is beneficial in retaining hematological and performance adaptations. Methods Eighteen mixed martial art fighters completed a 3-weeks natural altitude training camp at 2418 m. Afterwards, participants were randomly assigned to a living high-training low (12 h/d at a simulated altitude of 2800 m) group (LHTL, n = 9) or a living low-training low group (LLTL, n = 9) for a 3-week sea-level training period. At baseline and after return to sea level, hematological [hemoglobin mass (Hbmass) on days 2, 6, 9, 12, 15 and 21] and performance (3000 m time trial and maximal oxygen uptake on days 4, 6, 9, 15 and 21) markers were assessed. Results Mean Hbmass increased from baseline to day 2 (11.7 ± 0.9 vs. 12.4 ± 1.3 g/kg; + 6.6 ± 7.5%; P < 0.05). While Hbmass remained elevated above baseline in LHTL (P < 0.001), it returned near baseline levels from day 9 in LLTL. Irrespective of groups, mean V̇O2max was only elevated above baseline at day 2 (+ 4.5 ± 0.8%) and day 9 (+ 3.8 ± 8.0%) (both P < 0.05). Compared to baseline, 3000 m running time decreased at day 4 (– 3.1 ± 3.3%; P < 0.05) and day 15 (– 2.8 ± 2.3%; P < 0.05) only. Conclusions Despite re-exposure to hypoxia allowing a recovery of the hypoxic stimulus to retain Hbmass gains from previous altitude sojourn, there is no performance advantage of this practice above sea level residence. Our results also give support to empirical observations describing alternance of periods of optimal and attenuated performance upon return to sea level. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Comparative Efficacy of Oral Calcitonin-Gene–Related Peptide Antagonists for the Treatment of Acute Migraine: Updated Meta-analysis

xlomafota.13 shared this article with you from Inoreader Comparative Efficacy of Oral Calcitonin-Gene–Related Peptide Antagonists for the Treatment of Acute Migraine: Updated Meta-analysis Via Latest Results for Clinical Drug Investigation Abstract Background and Objective The calcitonin gene-related peptide (CGRP) is a new therapeutic target in migraine—a common disorder resulting in reduced quality of life. The aim of this study was to compare the clinical efficacy of five oral CGRP antagonists with that of a placebo and triptans against acute migraine via meta-analysis. Methods Suitable randomized controlled trials (RCTs) were searched in PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (WHO-ICTRP) to compare the efficacy of oral CGRP antagonists with that of a placebo and triptans against acute migraine. Review Manager 5.4 was used for data analysis. Results A total of 17 trials met the eligibility criteria and were studied in detail. The CGRP antagonists were significantly more effective than the placebo with respect to outcomes such as pain freedom at 2 h post-dose (odds ratio = 2.11; 95% confidence intervals [CIs] = 1.90–2.35) and pain relief at 2 h post-dose (odds ratio = 1.94; 95% CIs = 1.70–2.21). Similar results were found in the subgroup analysis conducted to compare the clinical efficacy of the FDA-approved oral CGRP antagonists (ubrogepant and rimegepant) and placebo. However, the CGRP antagonists were less effective than the triptans with respect to outcomes such as pain freedom at 2 h post-dose (odds ratio = 0.66; 95% CIs = 0.55–0.78) and pain relief at 2 h post-dose (odds ratio = 0.78; 95% CIs = 0.66–0.93). Conclusion CGRP antagonists are more effective than placebo against acute migraine; however, further studies are required to consider CGRP antagonists as standard first-line treatment for acute migraine instead of triptans, especially in patients with co-existing cardiovascular diseases. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

An Oral-mucosa-on-a-chip sensitively evaluates cell responses to dental monomers

xlomafota.13 shared this article with you from Inoreader An Oral-mucosa-on-a-chip sensitively evaluates cell responses to dental monomers Via Latest Results for Biomedical Microdevices Abstract Knowledge of human gingival cell responses to dental monomers is critical for the development of new dental materials. Testing standards have been developed to provide guidelines to evaluate biological functionality of dental materials and devices. However, one shortcoming of the traditional testing platforms is that they do not recapitulate the multi-layered configuration of gingiva, and thus cannot evaluate the layer-specific cellular responses. An oral mucosa-chip with two cell layers was previously developed as an alternative platform to assess the oral mucosa responses to dental biomaterials. The mucosa-chip consists of an apical keratinocyte layer attached to a fibroblast-embedded collagen hydrogel through interconnecting pores in a three-microchannel network. Here, cell responses in the mucosa-chip were evaluated against 2-hydroxyethyl methacrylate (HEMA), a common monomer used in restorative and aesthetic dentistry. The response of mucosal cell viabilit y was evaluated by exposing the chip to HEMA of concentrations ranging from 1.56 to 25 mM and compared to cells in conventional well-plate monoculture. The co-cultured cells were then stained and imaged with epifluorescence and confocal microscopy to determine the layer-specific responses to the treatment. Mucosa-chips were demonstrated to be more sensitive to assess HEMA-altered cell viability than well-plate cultures, especially at lower doses (1.56 and 6.25 mM). The findings suggest that the mucosa-chip is a promising alternative to traditional platforms or assays to test a variety of biomaterials by offering a multi-layered tissue geometry, accessible layer-specific information, and higher sensitivity in detecting cellular responses. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Comparison of universal screening in major lynch-associated tumors: a systematic review of literature

xlomafota.13 shared this article with you from Inoreader Comparison of universal screening in major lynch-associated tumors: a systematic review of literature Via Latest Results for Familial Cancer Abstract Lynch syndrome (LS) is associated with an increased lifetime risk of several cancers including colorectal (CRC), endometrial (EC), ovarian (OC), urinary (UT) and sebaceous tumors (ST). The benefit for universal screening in CRC and EC is well known. However, this benefit in other major lynch-associated tumors is unclear. We performed a systematic review of all published articles in the MEDLINE database between 2005 to 2017 to identify studies performing universal screening for LS in unselected CRC, EC, OC, UT and ST. All cases with MSI-H (instability in two or more markers) or missing one or more proteins on IHC testing were considered screening positive. Cases with MLH1 promoter hypermethylation or BRAF mutation positive were considered to have somatic mutations. A total of 3788 articles were identified in MEDLINE yielding 129 study arms from 113 studies. The overall pooled yield of universal LS screening and germline mismatch gene mutation was significantly dif ferent across the major LS-associated tumors (Mann Whitney test, p < 0.001). The pooled screening yield was highest in ST [52.5% (355/676), 95% CI 48.74–56.26%] followed by EC [22.65% (1142/5041), 95% CI 21.54–23.86%], CRC [11.9% (5649/47,545), 95% CI 11.61–12.19%], OC [11.29% (320/2833), 95% CI 10.13–12.47%] and UT [11.2% (31/276), 95% CI 7.48–14.92%]. ST also had the highest pooled germline positivity for mismatch repair gene mutation [18.8%, 33/176, 95%CI 13.03–24.57], followed by EC [2.6% (97/3765), 95% CI 2.09–3.11], CRC [1.8% (682/37,220), 95% CI 1.66–1.94%], UT [1.8%(3/164), 95% CI − 0.24–3.83%] and OC [0.83%(25/2983), 95% CI 0.48–1.12%]. LS screening in EC yielded significantly higher somatic mutations compared to CRC [pooled percentage 16.94% [(538/3176), 95%CI 15.60–18.20%] vs. 5.23% [(1639/26,152), 95% CI 4.93–5.47%], Mann Whitney test, p < 0.0001. Universal LS testing should be routinely performed in OC, UT and STs in addition to C RC and EC. Our findings also support consideration for IHC and somatic mutation testing before germline testing in EC due to higher prevalence of somatic mutations as well as germline testing in all patients with ST. Our results have implications for future design of LS screening programs and further studies are needed to assess the cost effectiveness and burden on genetic counselling services with expanded universal testing for LS. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

ACE-2-interacting Domain of SARS-CoV-2 (AIDS) Peptide Suppresses Inflammation to Reduce Fever and Protect Lungs and Heart in Mice: Implications for COVID-19 Therapy

xlomafota.13 shared this article with you from Inoreader ACE-2-interacting Domain of SARS-CoV-2 (AIDS) Peptide Suppresses Inflammation to Reduce Fever and Protect Lungs and Heart in Mice: Implications for COVID-19 Therapy Via Latest Results for Journal of Neuroimmune Pharmacology Abstract COVID-19 is an infectious respiratory illness caused by the virus strain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and until now, there is no effective therapy against COVID-19. Since SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) for entering into host cells, to target COVID-19 from therapeutic angle, we engineered a hexapeptide corresponding to the ACE2-interacting domain of SARS-CoV-2 (AIDS) that inhibits the association between receptor-binding domain-containing spike S1 and ACE-2. Accordingly, wild type (wt), but not mutated (m), AIDS peptide inhibited SARS-CoV-2 spike S1-induced activation of NF-κB and expression of IL-6 in human lungs cells. Interestingly, intranasal intoxication of C57/BL6 mice with recombinant SARS-CoV-2 spike S1 led to fever, increase in IL-6 in lungs, infiltration of neutrophils into the lungs, arrhythmias, and impairment in locomotor activities, mimicking some of the important symptoms of COVID-19. Howe ver, intranasal treatment with wtAIDS, but not mAIDS, peptide reduced fever, protected lungs, improved heart function, and enhanced locomotor activities in SARS-CoV-2 spike S1-intoxicated mice. Therefore, selective targeting of ACE2-to-SARS-CoV-2 interaction by wtAIDS may be beneficial for COVID-19. Graphical Abstract View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prevalence and predictors of small intestinal bacterial overgrowth in systemic sclerosis: a systematic review and meta-analysis

xlomafota.13 shared this article with you from Inoreader Prevalence and predictors of small intestinal bacterial overgrowth in systemic sclerosis: a systematic review and meta-analysis Via Latest Results for Clinical Rheumatology Abstract The reported prevalence of small intestinal bacterial overgrowth (SIBO) among patients with systemic sclerosis (SSc) is highly variable. We conducted this systematic review and meta-analysis to estimate the prevalence and identify predictors of SIBO in SSc by summarizing all of the available data. A comprehensive literature search of the PubMed, Cochrane Library, and EMBASE databases from inception to July 2020 was conducted for studies correlating SIBO with SSc. Studies were screened, and relevant data were extracted and analyzed. The pooled prevalence of SIBO among SSc patients and the odds ratio (OR) of SIBO among SSc patients compared with healthy controls were calculated. Furthermore, predictors of SIBO in SSc were evaluated. Fourteen studies containing 700 SSc patients and 217 healthy controls met the inclusion criteria. The pooled prevalence of SIBO in SSc was 34% (95% CI 27–42%). The OR of SIBO in SSc patients was 12.51 (95% CI 6.51–24.03) compared wi th the healthy controls. Subgroup analyses showed that the prevalence of SIBO in SSc was higher in studies using the lactulose hydrogen breath test (LHBT) for diagnosis (56%, 95% CI 46–67%) compared with those that used the glucose hydrogen breath test (GHBT) (27%, 95%CI 20–35%) and a jejunal aspirated culture (JAC) (35%, 95%CI 25–51%). The prevalence of SIBO in SSc was higher in studies conducted in Western countries (38%, 95% CI 31–47%) than those conducted in Asian countries (15%, 95%CI 10–23%), and the prevalence of SIBO in the SSc population defined by ACR-EULAR 2013 (50%, 95% CI 0.21–0.79) was higher than the prevalence defined by ACR 1980 (30%, 95% CI 0.17–0.42) or other criteria (32%, 95% CI 0.16–0.48) Moreover, the risk of diarrhea was higher in SSc patients with SIBO than those without SIBO (OR 8.82, 95% CI 4.09–19, P < 0.00001); gender, SSc subset, digital ulcer, and pulmonary fibrosis do not seem to be associated with SIBO in SSc. Antibiotic therapy seems to be effective with SIBO in SSc patients. Approximately one-third of SSc patients tested positive for SIBO with a significantly increased risk over the controls. The prevalence of SIBO in SSc varied according to the SIBO diagnostic test performed, geographic area, and SSc diagnostic criteria. The presence of diarrhea may be a predictor of SIBO in SSc. Antibiotic treatment can lead to eradication of SIBO and gastrointestinal symptomatic improvement in SSc patients. Key Points • The pooled prevalence of SIBO in SSc patients was 34%, which varied according to the SIBO diagnostic test performed, geographic area and SSc diagnostic criteria. • The risk of SIBO in SSc was increased by nearly thirteenfold compared to the healthy controls. • Diarrhoea, but not gender, SSc subset, digital ulcer and pulmonary fibrosis, was associated with SIBO in SSc patients. • For SSc patients with SIBO, antibiotic treatment can lead to eradication of SIBO and gastrointestinal symptomatic improvement. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The association of the progression of knee osteoarthritis with high-sensitivity CRP in community-dwelling people—the Yakumo study

xlomafota.13 shared this article with you from Inoreader The association of the progression of knee osteoarthritis with high-sensitivity CRP in community-dwelling people—the Yakumo study Via Latest Results for Clinical Rheumatology Abstract Objective We aimed to investigate the relationship between high-sensitivity CRP (hs-CRP) levels and the knee osteoarthritis (KOA) status and whether high hs-CRP levels predict the progression of clinical KOA in community-dwelling people. Methods We enrolled 247 subjects (male, n = 99; female, n = 148) who participated in the "Yakumo study" at least twice from 2003 to 2008. The KOA was evaluated by knee X-ray using the knee osteoarthritis computer-aided diagnosis (KOACAD) measurement system to obtain the mJSW, the size of the osteophyte area (OPA), and femorotibial angle (FTA). The pain intensity of the knee joint was measured using a visual analog scale (VAS, 0–100). First, we performed a multiple regression analysis to assess the relationship between the initial hs-CRP and mJSW, OPA, FTA, and VAS. Second, we examined the correlated coefficients between the amount of change hs-CRP and radiographic progressions and VAS changes. Third, we divided into two groups. Group H elevated hs-CRP levels (> 0.1 mg/dl). We picked up the subject matched to Group H according to BMI, age, sex, and medial mJSW at baseline in a 1:1 ratio; these participants were classified as the control group (Group L). The Mann-Whitney U test was used to compare the demographic data between the two groups. P values of < 0.05 were considered to indicate statistical significance. Results The initial hs-CRP was a significant explanatory factor for mJSW and VAS change in multiple regression analysis. The change of VAS value negatively correlated with the change of hs-CRP. Besides, the change of hs-CRP did not correlate with the radiographical change. Among these subjects, 55 had elevated hs-CRP levels (> 0.1 mg/dl) (Group H). Among the 192 subjects whose hs-CRP levels were ≤ 0.1 mg/dl, 55 subjects were matched to patients in Group H according to the age, sex, BMI, and average minimum joint space width (mJSW) at baseline and were used as a control group (Group L). The narrowing of the medial mJSW and the amount of change in OPA in group H were significantly greater than group L. The amount of change in FTA and VAS scores did not differ between the two groups. Conclusion Hs-CRP levels would be significantly associated with the progression of knee osteoarthritis. Key Points • We investigated the relationship between hs-CRP levels and the progression and the pain of osteoarthritis knee. • We used a KOACAD system, which can measure the medial and lateral joint space narrowing, osteophyte, and femoral-tibia angle from plain radiographs automatically. • Hs-CRP levels were significantly associated with the progression of knee osteoarthritis. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.