The recent novel coronavirus disease (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is seeing a rapid increase in infected patients worldwide. The host ...immune response to SARS-CoV-2 appears to play a critical role in disease pathogenesis and clinical manifestations. SARS-CoV-2 not only activates antiviral immune responses, but can also cause uncontrolled inflammatory responses characterized by marked pro-inflammatory cytokine release in patients with severe COVID-19, leading to lymphopenia, lymphocyte dysfunction, and granulocyte and monocyte abnormalities. These SARS-CoV-2-induced immune abnormalities may lead to infections by microorganisms, septic shock, and severe multiple organ dysfunction. Therefore, mechanisms underlying immune abnormalities in patients with COVID-19 must be elucidated to guide clinical management of the disease. Moreover, rational management of the immune responses to SARS-CoV-2, which includes enhancing anti-viral immunity while inhibiting systemic inflammation, may be key to successful treatment. In this review, we discuss the immunopathology of COVID-19, its potential mechanisms, and clinical implications to aid the development of new therapeutic strategies against COVID-19.
Tumor cells often exhibit augmented capacity to maintain endoplasmic reticulum (ER) homeostasis under adverse conditions, yet the underlying mechanisms are not well defined. Here, through the ...evaluation of all human TRIM proteins, we find that TRIM25 is significantly induced upon ER stress. Upregulation of TRIM25 ameliorates oxidative stress, promotes ER-associated degradation (ERAD), and reduces IRE1 signaling in the UPR pathway. In contrast, depletion of TRIM25 leads to ER stress and attenuates tumor cell growth in vitro and in vivo. Mechanistically, TRIM25 directly targets Keap1 by ubiquitination and degradation. This leads to Nrf2 activation, which bolsters anti-oxidant defense and cell survival. TRIM25 expression is positively associated with Nrf2 expression and negatively with Keap1 expression in hepatocellular carcinoma (HCC) xenografts and specimens. Moreover, high TRIM25 expression correlates with poor patient survival in HCC. These findings reveal TRIM25 as a regulator of ER homeostasis and a potential target for tumor therapy.
Green tea catechins have received significant attention due to their potent antioxidant activity as well as diverse biological properties. Stabilizing and protecting catechins from degradation is ...very important but challenging. In this work, a nanosized edible
γ
-cyclodextrin-based metal–organic framework (CD-MOF) was designed and fabricated by a facile vapor diffusion route and applied for the encapsulation of a model green tea catechin, (-)-epigallocatechin gallate (EGCG) for the first time. Downsizing CD-MOF to the nanoscale is a suitable method to tackle down new applications. Significantly, the antioxidant activity results show that the CD-MOF-EGCG can remarkably enhance the antioxidant activity in alkaline solutions, as compared to that of free EGCG. Furthermore, the prepared CD-MOF-EGCG showed strong cancer cell growth inhibitory effects on C6 cells as confirmed by the cell viability assay. This work demonstrates that such safe and nontoxic nanoscale CD-MOF-based porous materials hold great promise for applications in the field of stabilization of catechins for biomedical applications.
Tea polyphenols find a wide range of applications in food, medical and pharmaceutical fields owing to their multi-health benefits including antioxidant and antibacterial activities, cancer ...prevention, anti-radiation and immune enhancement. However, the low absorption rate of tea polyphenols impedes their bioactivity in vivo. The low absorption and bioavailability have been attributed to their poor stability, passive diffusion, and active efflux in the gastrointestinal (GI) tract. Nanoparticle delivery system based on chitosan (CS), a natural biomaterial, has been widely applied in pharmaceutical field to enhance absorption of bioactive compounds. A few studies reported the enhanced absorption and bioavailability of tea polyphenols by the application of chitosan nanoparticles. This review describes the fabrication methods and potential benefits of chitosan nanoparticles as delivery systems for tea polyphenols for their enhanced absorption in the GI tract. In addition, challenges and future trends of chitosan nanoparticles as a carrier for oral delivery of tea polyphenols are also discussed.
Chitosan nanoparticles enhance the intestinal absorption of tea polyphenols. Display omitted
•The low absorption rate of tea polyphenols impedes their bioactivity in vivo.•Nanoparticle delivery system based on chitosan can enhance absorption of bioactive compounds.•The fabrication methods and potential benefits of chitosan nanoparticles in tea polyphenols delivery were described.•The challenges and future trends of chitosan nanoparticles as a carrier for oral delivery of tea polyphenols are discussed.
•Nitrogen-containing volatiles were formed during Oolong tea processing.•Pyrazines were detected in model thermal reaction of l-theanine with d-glucose.•l-Theanine enhanced 2,5-dimethylpyrazine ...production during Oolong tea processing.•The contribution of l-theanine to Oolong tea aroma formation was firstly demonstrated.
l-Theanine, the most abundant amino acid in tea, is widely believed to be associated with the tea taste, however, its contribution to the formation of tea aroma is still unknown. Volatiles were determined and nitrogen-containing compounds formed during manufacturing processes were quantified. Lower levels of total sugar and l-theanine were detected in the Oolong tea product undergoing full fire processing (FFOT) suggesting that l-theanine probably involved in the volatile formation during manufacturing processes. Methylpyrazine and 2,5-dimethylpyrazine, two newly formed compounds in FFOT, together with other volatiles were successfully detected in a model thermal reaction of d-glucose and l-theanine (GT-MTR) but not detectable in thermal reactions with single d-glucose (G-MTR) or l-theanine (T-MTR). The concentration of 2,5-dimethylpyrazine increased significantly by adding additional l-theanine to 2nd roasted tea. Our study demonstrated that l-theanine, at least partly, contributed to the formation of 2,5-dimethylpyrazine, a key roasted peanutty flavor in Oolong tea.
Adoptive cell therapies (ACTs) have existed for decades. From the initial infusion of tumor-infiltrating lymphocytes to the subsequent specific enhanced T cell receptor (TCR)-T and chimeric antigen ...receptor (CAR)-T cell therapies, many novel strategies for cancer treatment have been developed. Owing to its promising outcomes, CAR-T cell therapy has revolutionized the field of ACTs, particularly for hematologic malignancies. Despite these advances, CAR-T cell therapy still has limitations in both autologous and allogeneic settings, including practicality and toxicity issues. To overcome these challenges, researchers have focused on the application of CAR engineering technology to other types of immune cell engineering. Consequently, several new cell therapies based on CAR technology have been developed, including CAR-NK, CAR-macrophage, CAR-gammadeltaT, and CAR-NKT. In this review, we describe the development, advantages, and possible challenges of the aforementioned ACTs and discuss current strategies aimed at maximizing the therapeutic potential of ACTs. We also provide an overview of the various gene transduction strategies employed in immunotherapy given their importance in immune cell engineering. Furthermore, we discuss the possibility that strategies capable of creating a positive feedback immune circuit, as healthy immune systems do, could address the flaw of a single type of ACT, and thus serve as key players in future cancer immunotherapy. Keywords: Adoptive cell therapy, Chimeric antigen receptor, T cell receptor, Cancer therapy, Gene transduction
Free amino acids, including theanine, glutamine and glutamate, contribute greatly to the pleasant taste and multiple health benefits of tea. Amino acids in tea plants are mainly synthesized in roots ...and transported to new shoots, which are significantly affected by nitrogen (N) level and forms. However, the regulatory amino acid metabolism genes have not been systemically identified in tea plants. Here, we investigated the dynamic changes of free amino acid contents in response to N deficiency and forms in tea plant roots, and systemically identified the genes associated amino acid contents in individual metabolism pathways. Our results showed that glutamate-derived amino acids are the most dynamic in response to various forms of N and N deficiency. We then performed transcriptomic analyses of roots treated with N deficiency and various forms of N, and differentially expressed amino acid metabolic genes in each pathway were identified. The analyses on expression patterns and transcriptional responses of metabolic genes to N treatments provided novel insights for the molecular basis of high accumulation of theanine in tea plant root. These analyses also identified potential regulatory genes in dynamic amino acid metabolism in tea plant root. Furthermore, our findings indicated that the dynamic expression levels of CsGDH, CsAlaDC, CsAspAT, CsSDH, CsPAL, CsSHMT were highly correlated with changes of amino acid contents in their corresponding pathways. Herein, this study provides comprehensive insights into transcriptional regulation of amino acid metabolism in response to nitrogen deficiency and nitrogen forms in tea plant root.
The attachment of cells to the extracellular matrix (ECM) is the hallmark of structure-function stability and well-being. ECM detachment in localized tumors precedes abnormal dissemination of tumor ...cells culminating in metastasis. Programmed cell death (PCD) is activated during tumorigenesis to clear off ECM-detached cells through "anoikis." However, cancer cells develop several mechanisms for abrogating anoikis, thus promoting their invasiveness and metastasis. Specific factors, such as growth proteins, pH, transcriptional signaling pathways, and oxidative stress, have been reported as drivers of anoikis resistance, thus enhancing cancer proliferation and metastasis. Recent studies highlighted the key contributions of metabolic pathways, enabling the cells to bypass anoikis. Therefore, understanding the mechanisms driving anoikis resistance could help to counteract tumor progression and prevent metastasis. This review elucidates the dynamics employed by cancer cells to impede anoikis, thus promoting proliferation, invasion, and metastasis. In addition, the authors have discussed other metabolic intermediates (especially amino acids and nucleotides) that are less explored, which could be crucial for anoikis resistance and metastasis.
Synaptic refinement improves synaptic efficiency, which provides a possibility to improve memory in Alzheimer's disease (AD). In the current study, we aimed to investigate the role of L-theanine, a ...natural constituent in green tea, in hippocampal synaptic transmission and to assess its potential to improve memory in transgenic AD mice. Initially, we found that L-theanine bath application facilitated hippocampal synaptic transmission and reduced paired-pulse facilitation (PPF). These effects were blocked by antagonists of N-methyl-D-aspartic acid receptors and the dopamine D1/5 receptor, and a selective protein kinase A (PKA) inhibitor. Moreover, L-theanine enhanced PKA phosphorylation via dopamine D1/5 receptor activation. L-theanine did not influence hippocampal long-term potentiation (LTP) in the slices obtained from wild-type mice, but rescued the impairment of hippocampal LTP in AD mice. Importantly, systemic application of L-theanine also improved memory and hippocampal LTP in AD mice. Our results demonstrate that L-theanine administration promotes hippocampal dopamine and noradrenaline release, and stimulates PKA phosphorylation. Moreover, the rescued hippocampal LTP in AD mice could be impaired by a PKA inhibitor. Our data reveal that L-theanine ameliorates the impairment of memory and hippocampal LTP in AD mice, likely through dopamine D1/5 receptor-PKA pathway activation. These data warrant the consideration of L-theanine as a candidate for the treatment of AD.
L-theanine incubation facilitated hippocampal synaptic transmission. Especially, the facilitation was blocked by antagonists of N-methyl-D-aspartic acid (NMDA) receptors, protein kinase A (PKA), and dopamine D1/5 receptor. Moreover, L-theanine enhanced PKA phosphorylation via activating dopamine D1/5 receptor. Theanine modification rescued the impairment of hippocampal LTP in AD mice. Systemic application of L-theanine improved memory and hippocampal LTP in AD mice. The mechanisms demonstrated that L-theanine administration promoted hippocampal dopamine and noradrenaline release, and promoted PKA phosphorylation. Collectively, L-theanine facilitates hippocampal synaptic efficiency and ameliorates the impairment of memory and hippocampal LTP, likely through dopamine D1/5 recepotr-PKA pathway. These data might warrant L-theanine to be a candidate for treatment of AD. Display omitted
•L-theanine facilitates hippocampal synaptic transmission through the dopamine D1/5 receptor-PKA pathway.•L-theanine improves memory and hippocampal LTP in AD mice.•L-theanine elevates hippocampal dopamine and NA levels in AD mice.•L-theanine activates PKA in the hippocampus.
White teas are produced in the simple process of withering and drying the tender leaves of the plant
Camellia sinensis.
Tea aroma created in this way exhibits a unique profile. Studies were carried ...out on the molecular contributors to the aroma character of the four well-known traditional white teas: Baihaoyingzhen (BHYZ), Baimudan (BMD), Gongmei (GM), and Shoumei (SM). Volatiles of the tea infusions were enriched by solvent partitioning followed by solid-phase extraction (SPE). The highly volatile compounds were captured by headspace solid-phase microextraction (HS SPME). Gas chromatography–olfactometry (GC-O) experiments discovered 37 odor-active components. Quantitation of aroma compounds was achieved using the method of standard addition (SAM). Calculation of odor activity value (OAV) and aroma reconstitution experiments revealed that the aroma profiles of the four white teas were attributed by 15 compounds, although a total of 179 volatile components were found in the extracts. BHYZ had distinct floral, fruity, and sweet characters, while BMD, GM, and SM had stronger woody and fermented notes. The major aroma contributors to the floral and sweet characters were geraniol and linalool for BHYZ and BMD; 2-phenylethanol and phenylacetaldehyde for GM and SM. The compounds produced from amino acid reactions during tea manufacturing, e.g. dimethyl sulfide, 3-methylbutanal, phenylacetaldehyde, etc., formed the basis of fruity and refreshing attributes. Degradation products of glycosides and carotenoids, such as geraniol, linalool, and ionones, contributed to the essential floral and sweet characters of the white teas.
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