Spices and herbs have been in use for centuries both for culinary and medicinal purposes. Spices not only enhance the flavor, aroma, and color of food and beverages, but they can also protect from ...acute and chronic diseases. More Americans are considering the use of spices and herbs for medicinal and therapeutic/remedy use, especially for various chronic conditions. There is now ample evidence that spices and herbs possess antioxidant, anti-inflammatory, antitumorigenic, anticarcinogenic, and glucose- and cholesterol-lowering activities as well as properties that affect cognition and mood. Research over the past decade has reported on the diverse range of health properties that they possess via their bioactive constituents, including sulfur-containing compounds, tannins, alkaloids, phenolic diterpenes, and vitamins, especially flavonoids and polyphenols. Spices and herbs such as clove, rosemary, sage, oregano, and cinnamon are excellent sources of antioxidants with their high content of phenolic compounds. It is evident that frequent consumption of spicy foods was also linked to a lower risk of death from cancer and ischemic heart and respiratory system diseases. However, the actual role of spices and herbs in the maintenance of health, specifically with regards to protecting against the development of chronic, noncommunicable diseases, is currently unclear. This review highlights potential health benefits of commonly used spices and herbs such as chili pepper, cinnamon, ginger, black pepper, turmeric, fenugreek, rosemary, and garlic.
A total of 900 juvenile Jian carp (Cyprinus carpio var. Jian) (7.99 ± 0.02 g) were fed diets containing graded levels of xylanase at 220 (unsupplemented control), 650, 1070, 1480, 1810 and ...2470 U kg⁻¹ diet for 10 weeks to investigate the effects of xylanase levels on growth performance, intestinal enzyme activities and microflora. The per cent weight gain, feed efficiency, protein efficiency ratio, protein production value, lipid production value, ash production value, calcium production value and phosphorus retention ratio were significantly improved with increasing levels of xylanase up to a point, and thereafter declined (P < 0.05). The activities of trypsin, chymotrypsin, lipase and amylase in the hepatopancreas and intestine, activities of alkaline phosphatase, Na⁺, K⁺‐ATPase, creatine kinase and γ‐glutamyl transpeptidase in three intestinal segments were improved by dietary xylanase (P < 0.05). The amounts of Lactobacillus, Escherichia coli and Aeromonas were significantly affected by dietary xylanase levels (P < 0.05). In conclusion, xylanase supplementation improved growth performance, enhanced intestinal enzyme activities and influenced the balance of intestinal microflora of juvenile Jian carp. The optimal level of xylanase in juvenile Jian carp (7.99–99.16 g) based on PWG was 1259 U kg⁻¹ diet by the quadratic regression analysis.
Effective targeted therapy for non-small-cell lung cancer (NSCLC) patients with human epidermal growth factor receptor 2 (HER2) mutations remains an unmet need. This study investigated the antitumor ...effect of an irreversible pan-HER receptor tyrosine kinase inhibitor, pyrotinib.
Using patient-derived organoids and xenografts established from an HER2-A775_G776YVMA-inserted advanced lung adenocarcinoma patient sample, we investigated the antitumor activity of pyrotinib. Preliminary safety and efficacy of pyrotinib in 15 HER2-mutant NSCLC patients in a phase II clinical trial are also presented.
Pyrotinib showed significant growth inhibition of organoids relative to afatinib in vitro (P = 0.0038). In the PDX model, pyrotinib showed a superior antitumor effect than afatinib (P = 0.0471) and T-DM1 (P = 0.0138). Mice treated with pyrotinib displayed significant tumor burden reduction (mean tumor volume, −52.2%). In contrast, afatinib (25.4%) and T-DM1 (10.9%) showed no obvious reduction. Moreover, pyrotinib showed a robust ability to inhibit pHER2, pERK and pAkt. In the phase II cohort of 15 patients with HER2-mutant NSCLC, pyrotinib 400 mg resulted in a objective response rate of 53.3% and a median progression-free survival of 6.4 months.
Pyrotinib showed activity against NSCLC with HER2 exon 20 mutations in both patient-derived organoids and a PDX model. In the clinical trial, pyrotinib showed promising efficacy.
NCT02535507.
An epidemic of metabolic disorders such as obesity and diabetes is rising dramatically. Using natural products as potential preventive and therapeutic interventions for these disorders has drawn ...worldwide attention. Rosemary has been shown to lower blood glucose and cholesterol levels and mitigate weight gain in several in vivo studies. However, the mechanisms are essentially unknown. We investigated the effects of rosemary extract on metabolism and demonstrated that rosemary extract significantly increased glucose consumption in HepG2 cells. The phosphorylation of AMP-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase (ACC), was increased by rosemary extract. Rosemary extract also transcriptionally regulated the genes involved in metabolism, including SIRT1, PPARγ coactivator 1α (PGC1α), glucose-6-phosphatase (G6Pase), ACC, and low-density lipoprotein receptor (LDLR). Furthermore, the PPARγ-specific antagonist GW9662 diminished rosemary’s effects on glucose consumption. Overall, our study suggested that rosemary potentially increases liver glycolysis and fatty acid oxidation by activating AMPK and PPAR pathways.
While most of the intergalactic medium (IGM) today is permeated by ionized hydrogen, it was largely filled with neutral hydrogen for the first 700 million years after the big bang. The process that ...ionized the IGM (cosmic reionization) is expected to be spatially inhomogeneous, with fainter galaxies likely playing a significant role. However, we still have only a few direct constraints on the reionization process. Here we report spectroscopic confirmation of two galaxies and very likely a third galaxy in a group (hereafter EGS77) at redshift z = 7.7, merely 680 Myr after the big bang. The physical separation among the three members is <0.7 Mpc. We estimate the radius of ionized bubble of the brightest galaxy to be about 1.02 Mpc, and show that the individual ionized bubbles formed by all three galaxies likely overlap significantly, forming a large yet localized ionized region, indicative of inhomogeneity in the reionization process. It is striking that two of three galaxies in EGS77 are quite faint in the continuum, thanks to our selection using their Ly line emission in the narrowband filter. Indeed, one is the faintest spectroscopically confirmed galaxy yet discovered at such high redshifts. Our observations provide direct constraints on the process of cosmic reionization, and allow us to investigate the properties of sources responsible for reionizing the universe.
Abstract The purpose of this study was to evaluate a personalized orthognathic surgical guide (POSG) system for bimaxillary surgery without the use of surgical splint. Ten patients with dentofacial ...deformities were enrolled. Surgeries were planned with the computer-aided surgical simulation method. The POSG system was designed for both maxillary and mandibular surgery. Each consisted of cutting guides and three-dimensionally (3D) printed custom titanium plates to guide the osteotomy and repositioning the bony segments without the use of the surgical splints. Finally, the outcome evaluation was completed by comparing planned outcomes with postoperative outcomes. All operations were successfully completed using the POSG system. The largest root-mean-square deviations were 0.74 mm and 1.93° for the maxillary dental arch, 1.10 mm and 2.82° for the mandibular arch, 0.83 mm and 2.59° for the mandibular body, and 0.98 mm and 2.45° for the proximal segments. The results of the study indicated that our POSG system is capable of accurately and effectively transferring the surgical plan without the use of surgical splint. A significant advantage is that the repositioning of the bony segments is independent to the mandibular autorotation, thus eliminates the potential problems associated with the surgical splint.
MicroRNAs (miRNAs) are a family of 19-24 nucleotide non-coding RNAs with posttranscriptional regulatory functions. The involvement of miRNAs in normal hematopoiesis implies that deregulated miRNAs ...might contribute to leukemogenesis. To date, although certain miRNAs have been established a clear oncogenic role in hematological malignancies, other individual miRNAs potentially involved in human leukemogenesis still remain elusive. In this report, we showed that miR-142-3p was upregulated in human T-leukemic cell lines and primary T-leukemic cells isolated from T-cell acute lymphoblastic leukemia (T-ALL) patients and its expressive levels were correlated with patients' prognosis. Such an oncogenic role of miR-142-3p could be explained by its targeting cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and glucocorticoid receptor alpha (GRα). High levels of miR-142-3p resulted in low levels of cAMP and weak activity of PKA, thus relieving the inhibitory effect of PKA on T-leukemic cell proliferation. Meanwhile, miR-142-3p decreased GRα protein expression by directly targeting the 3'-untranslational region of GRα mRNA, leading to glucocorticoid resistance. Transfection of the miR-142-3p inhibitor effectively converted glucocorticoid resistance, because of the resultant increase of GRα expression and PKA activity. These findings suggest that miR-142-3p is critical in T-cell leukemogenesis and may serve as a potential therapeutic target in T-ALL patients.
Exposure to maternal tissue during in utero development imprints tolerance to immunologically foreign non-inherited maternal antigens (NIMA) that persists into adulthood. The biological advantage of ...this tolerance, conserved across mammalian species, remains unclear. Here, we show maternal cells that establish microchimerism in female offspring during development promote systemic accumulation of immune suppressive regulatory T cells (Tregs) with NIMA specificity. NIMA-specific Tregs expand during pregnancies sired by males expressing alloantigens with overlapping NIMA specificity, thereby averting fetal wastage triggered by prenatal infection and non-infectious disruptions of fetal tolerance. Therefore, exposure to NIMA selectively enhances reproductive success in second-generation females carrying embryos with overlapping paternally inherited antigens. These findings demonstrate that genetic fitness, canonically thought to be restricted to Mendelian inheritance, is enhanced in female placental mammals through vertically transferred maternal cells that promote conservation of NIMA and enforce cross-generational reproductive benefits.
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•Microchimeric maternal cells drive postnatal persistence of NIMA-specific tolerance•NIMA-specific immune suppressive Tregs selectively accumulate in female offspring•Overlap between NIMA and fetal antigen during pregnancy accentuates fetal tolerance•Cross-generational protection against fetal wastage enforced by NIMA tolerance
Selective accumulation of immune suppressive regulatory T cells in female offspring in response to maternal cell microchimerism enforces tolerance to overlapping fetal antigens during next-generation pregnancies. This highly conserved mechanism promotes reproductive fitness by preserving conservation of non-inherited maternal traits.