Sil1 is the causative gene of Marinesco-Sjӧgren Syndrome (MSS). The mutated Sil1 generates shortened SIL1 protein which will form aggregation and be degraded rapidly. Mental retardation is a major symptom of MSS which suggests a role of SIL1 in the development of the central nervous system, but how SIL1 functions remains unclear.

Although mesenchymal stromal cells (MSCs) have demonstrated beneficial effects on experimental acute respiratory distress syndrome (ARDS), preconditioning may be required to potentiate their therapeutic effects. Additionally, administration of cell-free products, such as extracellular vesicles (EVs) obtained from MSC-conditioned media, might be as effective as MSCs. In this study, we comparatively evaluated the effects of MSCs, preconditioned or not with serum collected from mice with pulmonary or extrapulmonary ARDS (ARDSp and ARDSexp, respectively), and the EVs derived from these cells on lung inflammation and remodeling in ARDSp and ARDSexp mice. Administration of MSCs (preconditioned or not), but not their EVs, reduced static lung elastance, interstitial edema, and collagen fiber content in both ARDSp and ARDSexp. Although MSCs and EVs reduced alveolar collapse and neutrophil cell counts in lung tissue, therapeutic responses were superior in mice receiving MSCs, regardless of preconditioning. Despite higher total cell, macrophage, and neutrophil counts in bronchoalveolar lavage fluid in ARDSp than ARDSexp, MSCs and EVs (preconditioned or not) led to a similar decrease. In ARDSp, both MSCs and EVs, regardless of preconditioning, reduced levels of tumor necrosis factor- (TNF-) α, interleukin-6, keratinocyte chemoattractant (KC), vascular endothelial growth factor (VEGF), and transforming growth factor- (TGF-) β in lung homogenates. In ARDSexp, TNF-α, interleukin-6, and KC levels were reduced by MSCs and EVs, preconditioned or not; only MSCs reduced VEGF levels, while TGF-β levels were similarly increased in ARDSexp treated either with saline, MSCs, or EVs, regardless of preconditioning. In conclusion, MSCs yielded greater overall improvement in ARDS in comparison to EVs derived from the same number of cells and regardless of the preconditioning status. However, the effects of MSCs and EVs differed according to ARDS etiology.

In present study, a DLLME-HPLC-UV method was developed and validated for the extraction, pre-concentration, and subsequently quantification of vitamin D3 (Vit D3) in milk and yogurt samples. In order to be able to extract Vit D3 from studied samples efficiently, the DLLME procedure was optimized with respect to the parameters affecting the extraction efficacy, where acetonitrile (2 mL as disperser solvent) resulting from the protein precipitation procedure was mixed with 80 µL carbon tetrachloride (as an extraction solvent) respectively. The extracted samples were quantitatively analyzed with a HPLC technique using a C8 column (250 mm × 4.6 mm, 5 μm) at room temperature (25 °C), mobile phase of acetonitrile/methanol (90:10% v/v) in isocratic elution mode at a flow rate of 1.2 mL/min and UV detection at 265 nm. The method validation results revealed that the method was linear in the concentration range of 2 to 60 ng/mL (r = 0.9997) with a LOD of 0.9 ng/mL and LLOQ of 2 ng/mL; the method was accurate (-2.1% ≤ RE% ≤ +0.6%) and precise (1.2% ≤RSD% ≤ 11.3%) and its recovery was in the range of 86.6 to 113.3%. The obtained results indicated that the method could be utilized as an easy to use technique for the monitoring Vit D3 in dairy products, especially milk and yogurt samples.

All sophisticated methods for direct determination of methanol require advanced instruments and high technical knowledge whose preparing them is very expensive in none developed and developing countries. This work reports a simple and efficient qualitative technique for semi determination of methanol content in herbal distillates by a new modified chromotropic acid method. The technique is based on the indirect detection of methanol after its oxidation and transforming to formaldehyde by chromotropic acid (formaldehyde specific color indicator). To measure methanol level in herbal distillates, a water diluted sample was mixed with 50 µL of sulfuric acid and potassium permanganate and after 5 min, followed by addition sodium bi-sulfite, chromotropic acid, and concentrated sulfuric acid in two separated steps and finally, eye comparing with four color standard tubes which gives a range of amount of methanol in the sample. The method has a good precision and accuracy and its Limit of Detection is 25 mgL-1. It is particularly suitable for semi quantitative measurement of methanol in herbal distillates not only in the production process quality control of workshops or small companies with no laboratory equipment and adequate financial properties but also the quality check of point of-sale samples from commercial markets. To the best of our knowledge, there isn't any report about such method.

The TiO2, which is a main material in the field of photocatalytic reactions, includes rutile and anatase phase. Titanium dioxide has possessed notice due to its promising applications in the environmental photocatalytic degradation of pollutants of organic compound in waste water and utilization of solar energy. The nanosized manganese titanate (pyrophanite) MnTiO3 was collected by oxidation of Mn(OH)2 with TiO2 powder in cetyltrimethylammonium bromide (CTAB) micelle solutions and the calcinations of the produced powders. Therefore, it was decided to determine the Mechanistic mitochondria toxicity of nanoparticles towards liver, kidney, heart, and brain via new and reliable methods. Our results showed that nanoparticles induced mitochondria dysfunction via an increase in ROS production and membrane potential collapse, correlated to cytochrome c release. Also, increased disturbance in oxidative phosphorylation was also shown by the decrease in ATP. Recent studies have suggested that nanoparticles leading to cytosolic release of lysosomal content, and ultimately apoptosis. This study suggests that mitochondrial oxidative stress and impairment of oxidative phosphorylation in vital organ Mitochondria may play a key role in manganese titanate toxicity.

One of the emerging therapeutic strategies for targeted therapy of cancer is the use of chimeric proteins. The p28 peptide has the ability of selective entrance and activating apoptosis in breast cancer cells. The NRC antimicrobial peptide showed cytotoxic activity on various breast cancer cell lines including drug-resistant cells and also on normal cells. Here we designed a chimeric protein consisting of these peptides to determine their targeted effects and to enhance their cytotoxic effects on breast cancer cells. The chimeric protein was cytotoxic to MDA-MB-231 and MCF7 breast cancer cell lines in a dose-dependent manner after 48 h of treatment. In addition, the cytotoxic effects of the p28 alone were significantly lower than the chimeric protein indicating the additive or enhanced effects of the two peptides. Flow cytometry analysis showed that the induced cell death is mediated via apoptosis. The designed chimeric protein had enhanced effects on breast cancer cell lines and exerted its anticancer effects on MCF7 breast cancer cells through mitochondrial caspase dependent and -independent apoptotic pathways. Taken together, the results of this study suggested the chimeric protein to be a reasonable anti-cancer agent which must be further evaluated by subsequent in-vitro and in-vivo preclinical studies.

Noscapine is a natural alkaloid with anti-angiogenesis activities. The aim of the present study was to examine the effect of noscapine on eutopic endometrium of endometriosis patients (EEE) and normal endometrium (NE) in a three-dimensional (3D) culture model. In this experimental in-vitro study, EEE (n = 8) and NE (n = 8) biopsies were taken from 16 reproductive aged women. The biopsies were cleared from blood and mucus. Each biopsy was cut into small fragments (1 × 1 mm) in a sterile condition. For 3D culture, the endometrial fragments were put between two layers of fibrin jell made of fibrinogen solution [3 mg/mL in Medium199 (M199) + thrombin]. Twenty-four wells of culture dish was divided into 5 groups for each biopsy: the control wells were treated with M199 containing 5% fetal bovine serum (FBS) while, the test wells were exposed to the same media containing one of the noscapine doses (10, 50, 100, and 200 μM). The expression of apoptotic genes, growth score, angiogenesis, and nitric oxide (NO) secretion were evaluated. The mean of growth score of groups exposed to 0, 10, 50, 100, and 200 μM were 2.2 ± 0.55, 1.7 ± 0.45, 1.44 ± 0.27, 0.29 ± 0.1, and 0.1 ± 0.08 in EEE, and also, 2.11 ± 0.6, 1.65 ± 0.5, 0.79 ± 0.41, 0.18 ± 0.1, and 0.1 ± 0.1 in NE, respectively, and the difference between the groups was significant (P < 0.05). The expression of apoptotic genes significantly increased while, the levels of Bcl-2 and Sirt1 reduced (P = 0.004). NO secretion reduced significantly (P < 0.05) in both EEE and NE groups. In conclusion, higher doses of noscapine showed inhibitory effect on growth and angiogenesis of EEE and NE.

A high prevalence of genetic polymorphisms increases sensitivity to warfarin therapy. In this study, we investigated 47 patients with effective long-term therapy by warfarin well-controlled by monitoring of International Normalised Ratio (INR). All patients were tested for gene polymorphisms VKORC1, CYP2C9*C2, and CYP2C9*C3, which were used for a dose calculation employing a program www.WarfarinDosing.org. The main goal was to investigate whether the warfarin doses determined by INR are in accordance with the doses calculated according to the pharmacogenetic algorithm. For this purpose, several chemometric tools, namely principal component analysis, cluster analysis, correlation analysis, correspondence analysis, Passing-Bablock regression, Bland-Altman method, descriptive statistics, and ANOVA were used. We also analysed the relationship between the dose of warfarin determined by INR and several constitutional and genetic factors. Statistically significant association between clinically optimized warfarin dose and indication for the treatment, age, and warfarin sensitivity determined by VKORC1, CYP2C9 gene polymorphisms were confirmed. Finally, we confirmed a good concordance between the INR determined warfarin doses and pharmacogenetic approach.

Toxoplasma gondii infection has public health importance and can lead to serious diseases in immunosuppressed patients, such as HIV cases. Appropriate control of T. gondii infection in HIV patients requires information about the prevalence of T. gondii antibodies and DNA in different population. In this study, we aimed to determine the prevalence of Toxoplasma gondii antibodies and DNA in HIV patients in Tehran, Iran.

The flexible barbell is purported to improve training gains compared with an Olympic steel barbell (SB) during the back squat exercise with Division I collegiate American football programs. The two bars loaded at 30% 1-repetition maximum were compared with ten trained Division I American football players (n = 10; age = 19.5 years; body mass = 89.4 kg; body height = 182.0 cm) completing 10 repetitions of the back squat exercise. Analysis included integrated-peak values of electromyography of the rectus femoris, biceps femoris, rectus abdominis, erector spinae, external oblique, vastus lateralis, ground reaction forces, and joint kinematics and kinetics of the hip, knee, and ankle. The flexible bar elicited significant increases in peak joint kinetics (Hip Moment: 229 ± 54 Nm vs. 209 ± 52 Nm; Hip Power: 494 ± 151 W vs. 382 ± 134 W; Knee Power: 305 ± 108 W vs. 241 ± 63 W), peak vertical ground reaction forces (1195 ± 209 N vs. 1120 ± 203 N), and muscle activity (Vastus Lateralis: 75.7 vs. 66.5%, Rectus Abdominis: 190 vs. 115%, Rectus Femoris: 69.8 vs. 59.9%, External Oblique: 115 vs. 69.0%). Greater vertical ground reaction forces, hip moment, hip power, knee power, and muscle activity of the vastus lateralis, rectus abdominis, rectus femoris, and external oblique suggest the FB provides biomechanical and physiological mechanisms for training gains over the SB for 30% of 1-repetition maximum loads.

Among all the common complications that occur after abdominal surgery, intestinal adhesion is perhaps the most unpleasant one. However, current methods to treat and prevent intestinal adhesion are limited; thus, exploring new methods to prevent and treat intestinal adhesion is greatly needed. In this study, we demonstrated that Danhong injection (DHI) may be used as a promising method to prevent and treat intra-abdominal adhesion in a rat model.

Nanofat can protect against ultraviolet B- (UVB-) induced damage in nude mice. Fat extract (FE) is a cell-free fraction isolated from nanofat that is enriched with a variety of growth factors.

Targeting aberrant metabolism is a promising strategy for inhibiting cancer growth and metastasis. Research is now geared towards investigating the inhibition of glycolysis for anticancer drug development. Betulinic acid (BA) has demonstrated potent anticancer activities in multiple malignancies. However, its regulatory effects on glycolysis and the underlying molecular mechanisms are still unclear. BA inhibited invasion and migration of highly aggressive breast cancer cells. Moreover, BA could suppress aerobic glycolysis of breast cancer cells presenting as a reduction of lactate production, quiescent energy phenotype transition, and downregulation of aerobic glycolysis-related proteins. In this study, glucose-regulated protein 78 (GRP78) was also identified as the molecular target of BA in inhibiting aerobic glycolysis. BA treatment led to GRP78 overexpression, and GRP78 knockdown abrogated the inhibitory effect of BA on glycolysis. Further studies demonstrated that overexpressed GRP78 activated the endoplasmic reticulum (ER) stress sensor PERK. Subsequent phosphorylation of eIF2α led to the inhibition of β-catenin expression, which resulted in the inhibition of c-Myc-mediated glycolysis. Coimmunoprecipitation assay revealed that BA interrupted the binding between GRP78 and PERK, thereby initiating the glycolysis inhibition cascade. Finally, the lung colonization model validated that BA inhibited breast cancer metastasis in vivo, as well as suppressed the expression of aerobic glycolysis-related proteins. In conclusion, our study not only provided a promising drug for aerobic glycolysis inhibition but also revealed that GRP78 is a novel molecular link between glycolytic metabolism and ER stress during tumor metastasis.

Cascade testing for cancer predisposition offers a highly efficient and cost-effective method for identifying individuals at increased risk for cancer, in whom targeted interventions can often improve survival. The aim of this study was to determine the impact of free cascade testing on uptake and identify other associated factors. Demographic and clinical data were gathered prospectively for 183 probands found to have a pathogenic variant associated with cancer predisposition and their 826 first-degree relatives (FDRs). The provision of free cascade testing was significantly associated with uptake (21.6% vs 6.1%; χ 2, P < 0.001). Relationship type between FDR and proband and FDR age also demonstrated significant associations, suggesting greater engagement amongst younger generations. Overall, 29.0% (53/183) of families had at least 1 FDR who underwent cascade testing. Of these families, 67.9% (36/53) had an uptake rate of at least 40.0%. Cost is a significant barrier to cascade testing uptake in Singapore. Tailored interventions targeting underrepresented groups and genetic counseling approaches supporting family communication and decision-making are necessary.

Notch/Dll4 involvement in cornea neovascularization (CRNV) and lymphangiogenesis is unclear. This study aimed to explore the role of notch signaling in basic fibroblast growth factor- (bFGF-) induced corneal lymphangiogenesis and hemangiogenesis.

The results of a tuberculosis (TB) active case finding (ACF) program, implemented by International Care Ministries (ICM) in the Philippines, were examined to understand how the presence of physical symptoms might influence ACF outcomes among extreme low-income Filipinos. ICM health staff implemented symptom screening in villages and suspected cases were referred to the closest rural health unit (RHU) for TB testing. ACF was carried out in Mindanao and the Visayas, across 16 different provinces. All participants were interviewed pre/postprogram, and screening outcomes were collected. A multilevel regression model was constructed to explore the effect of factors on the likelihood of getting tested. A total of 4635 individuals were screened; 1290 (27.8%) were symptom positive and referred. From those referred, 336 (7.2%) were tested for TB and 53 (1.1%) were TB positive. "Cough for more than two weeks" was associated with a 1.09 (95% CI 1.01, 1.15) times increase in likelihood of getting tested. The finding that the presence of cough is associated with higher rate of testing suggests that individuals in these settings might not know or believe that the lack of cough does not equate to lack of TB infection. While technologies and screening algorithms give us the ability to refine the 'supply' side of the TB screening, addressing the knowledge gap should improve 'demand'.

Neuropeptides exert their activity through binding to G protein-coupled receptors (GPCRs). GPCRs are well-known drug targets in the pharmaceutical industry and are currently discussed as targets to control pest insects. Here, we investigate the neuropeptide adipokinetic hormone (AKH) system of the desert locust Schistocerca gregaria. The desert locust is known for its high reproduction, and for forming devastating swarms consisting of billions of individual insects. It is also known that S. gregaria produces three different AKHs as ligands but has only one AKH receptor (AKHR). The AKH system is known to be essential for metabolic regulation, which is necessary for reproduction and flight activity.

Jerusalem artichoke (Helianthus tuberosus L.) is widely cultivated in Northwest China, and it has become an emerging economic crop that is rapidly developing. Because of its elevated inulin content and high resistance, it is widely used in functional food, inulin processing, feed, and ecological management. In this study, Illumina sequencing technology was utilized to assemble and annotate the complete chloroplast genome sequences of Jerusalem artichoke. The total length was 151,431 bp, including four conserved regions: A pair of reverse repeat regions (IRa 24,568 bp and IRb 24,603 bp), a large single-copy region (83,981 bp), and a small single-copy region (18,279 bp). The genome had a total of 115 genes, with 19 present in the reverse direction in the IR region. A total of 36 simple sequence repeats (SSRs) were identified in the coding and non-coding regions, most of which were biased toward A/T bases. A total of 32 SSRs were distributed in the non-coding regions. A comparative analysis of the chloroplast genome sequence of the Jerusalem artichoke and other species of the composite family revealed that the chloroplast genome sequences of plants of the composite family were highly conserved. Differences were observed in 24 gene loci in the coding region, with the degree of differentiation of the ycf2 gene being the most obvious. A phylogenetic analysis showed that H. petiolaris subsp. fallax had the closest relationship with Jerusalem artichoke, both members of the Helianthus genus. Selective locus detection of the ycf2 gene in eight species of the composite family was performed to explore adaptive evolution traits of the ycf2 gene in Jerusalem artichoke. The results show that there are significant and extremely significant positive selection sites at the 1239N and 1518R loci, respectively, indicating that the ycf2 gene has been subject to adaptive evolution. Insights from our assessment of the complete chloroplast genome sequences of Jerusalem artichoke will aid in the in-depth study of the evolutionary relationship of the composite family and provide significant sequencing information for the genetic improvement of Jerusalem artichoke.

Recent studies have indicated that circulating miRNAs could serve as accurate biomarkers for diagnosing nonalcoholic fatty liver disease (NAFLD). We aimed to assess the evidence on the probability of circulating miRNAs as new diagnostic biomarkers in patients with NAFLD.

Food antigens have been shown to participate in the etiopathogenesis of inflammatory bowel disease (IBD), but their clinical value in IBD is still unclear.