Genome-wide identification and functional analysis of the SiCIN gene family in foxtail millet (Setaria italica L.).

Cell wall invertase (CIN) is a vital member of plant invertase (INV) and plays a key role in the breakdown of sucrose. This enzyme facilitates the hydrolysis of sucrose into glucose and fructose, which is crucial for various aspects of plant growth and development. However, the function of CIN genes in foxtail millet (Setaria italica) is less studied. In this research, we used the blast-p of NCBI and TBtools for bidirectional comparison, and a total of 13 CIN genes (named SiCINs) were identified from foxtail millet by using Arabidopsis and rice CIN sequences as reference sequences. The phylogenetic tree analysis revealed that the CIN genes can be categorized into three subfamilies: group 1, group 2, and group 3. Furthermore, upon conducting chromosomal localization analysis, it was observed that the 13 SiCINs were distributed unevenly across five chromosomes. Cis-acting elements of SiCIN genes can be classified into three categories: plant growth and development, stress response, and hormone response. The largest number of cis-acting elements were those related to light response (G-box) and the cis-acting elements related to seed-specific regulation (RY-element). qRT-PCR analysis further confirmed that the expression of SiCIN7 and SiCIN8 in the grain was higher than that in any other tissues. The overexpression of SiCIN7 in Arabidopsis improved the grain size and thousand-grain weight, suggesting that SiCIN7 could positively regulate grain development. Our findings will help to further understand the grain-filling mechanism of SiCIN and elucidate the biological mechanism underlying the grain development of SiCIN.

A novel bispecific antibody drug conjugate targeting HER2 and HER3 with potent therapeutic efficacy against breast cancer.

Antibody drug conjugate (ADC) therapy has become one of the most promising approaches in cancer immunotherapy. Bispecific targeting could enhance the efficacy and safety of ADC by improving its specificity, affinity and internalization. In this study we constructed a HER2/HER3-targeting bispecific ADC (BsADC) and characterized its physiochemical properties, target specificity and internalization in vitro, and assessed its anti-tumor activities in breast cancer cell lines and in animal models. The HER2/HER3-targeting BsADC had a drug to antibody ratio (DAR) of 2.89, displayed a high selectivity against the target JIMT-1 breast cancer cells in vitro, as well as a slightly higher level of internalization than HER2- or HER3-monospecific ADCs. More importantly, the bispecific ADC potently inhibited the viability of MCF7, JIMT-1, BT474, BxPC-3 and SKOV-3 cancer cells in vitro. In JIMT-1 breast cancer xenograft mice, a single injection of bispecific ADC (3 mg/kg, i.v.) significantly inhibited the tumor growth with an efficacy comparable to that caused by combined injection of HER2 and HER3-monospecific ADCs (3 mg/kg for each). Our study demonstrates that the bispecific ADC concept can be applied to development of more potent new cancer therapeutics than the monospecific ADCs.

Characterization of a novel T cell-engaging bispecific antibody for elimination of L1CAM-positive tumors.

Neural cell adhesion molecule L1 (L1CAM) is a cell-surface glycoprotein involved in cancer occurrence and migration. Up to today, L1CAM-targeted therapy appeared limited efficacy in clinical trials although quite a few attempts by monoclonal antibody (mAb) or chimeric antigen receptor T-cell therapy (CAR-T) have been reported. Therefore, the development of new effective therapies targeting L1CAM is highly desirable. It has been demonstrated that T cell-engaging bispecific antibody (TCE) plays an effective role in cancer immunotherapy by redirecting the cytotoxic activity of CD3+ T cells to tumor cells, resulting in tumor cell death. In this study, we designed and characterized a novel bispecific antibody (CE7-TCE) based on the IgG-(L)-ScFv format, which targets L1CAM and CD3 simultaneously. In vitro, CE7-TCE induced specific killing of L1CAM-positive tumor cells through T cells. In vivo, CE7-TCE inhibited tumor growth in human peripheral blood mononuclear cell/tumor cell co-grafting models. To overcome the adaptive immune resistance (AIR) that impairs the efficacy of TCEs, we conducted a combination therapy of CE7-TCE with Pembrolizumab (anti-PD1 mAb), which enhanced the anti-tumor activity of CE7-TCE. Our results confirmed the feasibility of using L1CAM as a TCE target for the treatment of solid tumors and revealed the therapeutic potential of CE7-TCE combined with immune checkpoint inhibitors.

Re-Engineering Therapeutic Anti-Aß Monoclonal Antibody to Target Amyloid Light Chain.

Amyloidosis involves the deposition of misfolded proteins. Even though it is caused by different pathogenic mechanisms, in aggregate, it shares similar features. Here, we tested and confirmed a hypothesis that an amyloid antibody can be engineered by a few mutations to target a different species. Amyloid light chain (AL) and ß-amyloid peptide (Aß) are two therapeutic targets that are implicated in amyloid light chain amyloidosis and Alzheimer's disease, respectively. Though crenezumab, an anti-Aß antibody, is currently unsuccessful, we chose it as a model to computationally design and prepare crenezumab variants, aiming to discover a novel antibody with high affinity to AL fibrils and to establish a technology platform for repurposing amyloid monoclonal antibodies. We successfully re-engineered crenezumab to bind both Aß42 oligomers and AL fibrils with high binding affinities. It is capable of reversing Aß42-oligomers-induced cytotoxicity, decreasing the formation of AL fibrils, and alleviating AL-fibrils-induced cytotoxicity in vitro. Our research demonstrated that an amyloid antibody could be engineered by a few mutations to bind new amyloid sequences, providing an efficient way to reposition a therapeutic antibody to target different amyloid diseases.

Genome-wide DNase I-hypersensitive site assay reveals distinct genomic distributions and functional features of open chromatin in autopolyploid sugarcane.

The characterization of cis-regulatory DNA elements (CREs) is essential for deciphering the regulation of gene expression in eukaryotes. Although there have been endeavors to identify CREs in plants, the properties of CREs in polyploid genomes are still largely unknown. Here, we conducted the genome-wide identification of DNase I-hypersensitive sites (DHSs) in leaf and stem tissues of the auto-octoploid species Saccharum officinarum. We revealed that DHSs showed highly similar distributions in the genomes of these two S. officinarum tissues. Notably, we observed that approximately 74% of DHSs were located in distal intergenic regions, suggesting considerable differences in the abundance of distal CREs between S. officinarum and other plants. Leaf- and stem-dependent transcriptional regulatory networks were also developed by mining the binding motifs of transcription factors (TFs) from tissue-specific DHSs. Four TEOSINTE BRANCHED 1, CYCLOIDEA, and PCF1 (TCP) TFs (TCP2, TCP4, TCP7, and TCP14) and two ethylene-responsive factors (ERFs) (ERF109 and ERF03) showed strong causal connections with short binding distances from each other, pointing to their possible roles in the regulatory networks of leaf and stem development. Through functional validation in transiently transgenic protoplasts, we isolate a set of tissue-specific promoters. Overall, the DHS maps presented here offer a global view of the potential transcriptional regulatory elements in polyploid sugarcane and can be expected to serve as a valuable resource for both transcriptional network elucidation and genome editing in sugarcane breeding.

Widespread incomplete lineage sorting and introgression shaped adaptive radiation in the Gossypium genus.

Cotton (Gossypium) stands as a crucial economic crop, serving as the primary source of natural fiber for the textile sector. However, the evolutionary mechanisms driving speciation within the Gossypium genus remain unresolved. In this investigation, we leveraged 25 Gossypium genomes and introduced four novel assemblies-G. harknessii, G. gossypioides, G. trilobum, and G. klotzschianum (Gklo)-to delve into the speciation history of this genus. Notably, we encountered intricate phylogenies potentially stemming from introgression. These complexities are further compounded by incomplete lineage sorting (ILS), a factor likely to have been instrumental in shaping the swift diversification of cotton. Our focus subsequently shifted to the rapid radiation episode during a concise period in Gossypium evolution. For a recently diverged lineage comprising G. davidsonii, Gklo, and G. raimondii, we constructed a finely detailed ILS map. Intriguingly, this analysis revealed the non-random distribution of ILS regions across the reference Gklo genome. Moreover, we identified signs of robust natural selection influencing specific ILS regions. Noteworthy variations pertaining to speciation emerged between the closely related sister species Gklo and G. davidsonii. Approximately 15.74% of speciation structural variation genes and 12.04% of speciation-associated genes were estimated to intersect with ILS signatures. These findings enrich our understanding of the role of ILS in adaptive radiation, shedding fresh light on the intricate speciation history of the Gossypium genus.

A biomimetic cuproptosis amplifier for targeted NIR-II fluorescence/photoacoustic imaging-guided synergistic NIR-II photothermal immunotherapy.

The therapeutic efficacy of cuproptosis combined with phototheranostics is still hindered by easy copper efflux, nonspecific accumulation and limited light penetration depth. Here, a high-performance NIR-II semiconductor polymer was first synthesized through dual-donor engineering. Then a biomimetic cuproptosis amplifier (PCD@CM) was prepared by Cu(II)-mediated coordinative self-assembly of NIR-II ultrasmall polymer dots and the chemotherapeutic drug DOX, followed by camouflaging of tumor cell membranes. After homologous targeting delivery to tumor cells, overexpressed GSH in the tumor microenvironment (TME) triggers the disassembly of the amplifier and the release of therapeutic components through the reduction of Cu(II) to Cu(I), which enable NIR-II fluorescence/photoacoustic imaging-guided NIR-II photothermal therapy (PTT) and chemotherapy. The released Cu(I) induces the aggregation of lipoylated mitochondrial proteins accompanied by the loss of iron-sulfur proteins, leading to severe proteotoxic stress and eventually cuproptosis. NIR-II PTT and GSH depletion render tumor cells more sensitive to cuproptosis. The amplified cuproptosis sensitization provokes significant immune surveillance, triggering the immunogenic cell death (ICD) to promote cytotoxic T lymphocyte infiltration together with aPD-L1-mediated immune checkpoint blockade. This work proposes a new strategy to develop cuproptosis sensitization systems enhanced by NIR-II phototheranostics with homologous targeting and anti-tumor immune response capabilities.

Generation and Characterization of SORT1-Targeted Antibody-Drug Conjugate for the Treatment of SORT1-Positive Breast Tumor.

Antibody-drug conjugates (ADCs) have greatly improved the outcomes of advanced breast tumors. However, the treatment of breast tumors with existing ADCs is still hindered by many issues, such as tumor antigen heterogeneity and drug resistance. Therefore, ADCs against new targets would provide options for the treatment of these challenges. Sortilin-1 (SORT1) may be a promising target for ADC as it is upregulated in breast cancer. To evaluate the possibility of SORT1 as an ADC target, a humanized antibody_8D302 with high affinity against SORT1 was generated. Additionally, 8D302 was conjugated with MMAE and DXd to generate two ADCs_8D302-MMAE and 8D302-DXd, respectively. Both 8D302-MMAE and 8D302-DXd showed effective cytotoxicity against SORT1 positive breast tumor cell lines and induced bystander killing. Consequently, 8D302-MMAE showed relatively better anti-tumor activity than 8D302-DXd both in vitro and in vivo, but 8D302-DXd had superior safety profile and pharmacokinetics profile over 8D302-MMAE. Furthermore, SORT1 induced faster internalization and lysosomal trafficking of antibodies and had a higher turnover compared with HER2. Also, 8D302-DXd exhibited superior cell cytotoxicity and tumor suppression over trastuzumab-DXd, a HER2-targeted ADC. We hypothesize that the high turnover of SORT1 enables SORT1-targeted ADC to be a powerful agent for the treatment of SORT1-positive breast tumor.

Generation of a Novel SORT1×HER2 Bispecific Antibody-Drug Conjugate Targeting HER2-Low-Expression Tumor.

Human epidermal growth factor receptor 2 (HER2) is considered an ideal antibody-drug conjugate (ADC) target because the gene is overexpressed in many tumors compared to normal tissues. Multiple anti-HER2 ADCs conjugated with different toxic payloads bring benefits to patients with high HER2 expression. However, HER2-targeted ADC technology needs further optimization to improve its effect for the treatment of patients with low HER2 expression. We hypothesized that bispecific antibody-drug conjugate (bsADC) targeting HER2 and Sortilin-1 (SORT1) would overcome this limitation. SORT1 is a suitable target for pairing with HER2 to generate a bispecific antibody (BsAb) since the gene is co-expressed with HER2 in tumors and possesses rapid internalization. We developed a BsAb (bsSORT1×HER2) that exhibited strong binding and internalization activity on HER2-low-expression tumor cells and facilitated higher HER2 degradation. The bsSORT1×HER2 was further conjugated with DXd to generate a bsADC (bsSORT1×HER2-DXd) that showed strong cytotoxicity on HER2-low-expression tumor cells and antitumor efficacy in an MDA-MB-231 xenograft mice model. These results demonstrated that employment of a SORT1×HER2-targeted bsADC may be promising to improve the antitumor efficacy of HER2-targeted ADC for the treatment of tumors with low HER2 expression.

A protein kinase C α and ß inhibitor blunts hyperphagia to halt renal function decline and reduces adiposity in a rat model of obesity-driven type 2 diabetes.

Type 2 diabetes (T2D) and its complications can have debilitating, sometimes fatal consequences for afflicted individuals. The disease can be difficult to control, and therapeutic strategies to prevent T2D-induced tissue and organ damage are needed. Here we describe the results of administering a potent and selective inhibitor of Protein Kinase C (PKC) family members PKCα and PKCß, Cmpd 1, in the ZSF1 obese rat model of hyperphagia-induced, obesity-driven T2D. Although our initial intent was to evaluate the effect of PKCα/ß inhibition on renal damage in this model setting, Cmpd 1 unexpectedly caused a marked reduction in the hyperphagic response of ZSF1 obese animals. This halted renal function decline but did so indirectly and indistinguishably from a pair feeding comparator group. However, above and beyond this food intake effect, Cmpd 1 lowered overall animal body weights, reduced liver vacuolation, and reduced inguinal adipose tissue (iWAT) mass, inflammation, and adipocyte size. Taken together, Cmpd 1 had strong effects on multiple disease parameters in this obesity-driven rodent model of T2D. Further evaluation for potential translation of PKCα/ß inhibition to T2D and obesity in humans is warranted.

Circ_0035796 depletion inhibits transforming growth factor-ß1-induced pulmonary fibrosis in a miR-150-5p/L1CAM-dependent manner.

BACKGROUND: The pathogenesis of pulmonary fibrosis is not fully understood. Previous work has demonstrated the important role of circular RNA (circRNA) in pulmonary fibrosis development. This study aims to analyse the role of circ_0035796 in pulmonary fibrosis and the underlying mechanism. METHODS: Human foetal lung fibroblast 1 (HFL1) cells were treated with transforming growth factor-ß1 (TGF-ß1) to mimic a pulmonary fibrosis cell model. The expression of circ_0035796, microRNA-150-5p (miR-150-5p) and L1 cell adhesion molecule (L1CAM) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of L1CAM, collagen I and fibronectin was detected by Western blot. Cell viability was analysed by CCK-8 assay. Cell proliferation, invasion and migration were investigated by 5-Ethynyl-2'-deoxyuridine (EdU) assay, transwell invasion assay and wound-healing assay, respectively. The secretion of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) was analysed by Enzyme-linked immunosorbent assay (ELISA). Oxidative stress was assessed by detecting Superoxide Dismutase (SOD) activity and Malondialdehyde (MDA) level using commercial kits. The association of miR-150-5p with circ_0035796 and L1CAM was identified by dual-luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation (RIP) assay. RESULTS: Circ_0035796 and L1CAM expression were dramatically upregulated, while miR-150-5p expression was downregulated in TGF-ß1-treated HFL1 cells. TGF-ß1 treatment induced cell proliferation, migration, invasion, IL-6 and TNF-α secretion, and oxidative stress, whereas circ_0035796 depletion relieved these effects. In addition, circ_0035796 acted as a sponge of miR-150-5p and miR-150-5p combined with L1CAM. Moreover, miR-150-5p depletion attenuated circ_0035796 knockdown-mediated effects in TGF-ß1-exposed HFL1 cells. The regulation of miR-150-5p on TGF-ß1-induced fibroblast activation involved the downregulation of L1CAM. Further, circ_0035796 modulated L1CAM expression by interacting with miR-150-5p in TGF-ß1-exposed HFL1 cells. CONCLUSION: Circ_0035796 knockdown ameliorates TGF-ß1-induced pulmonary fibrosis through the miR-150-5p/L1CAM axis in vitro.

Exploring the Chemical and Biological Potential of Jamun (Syzygium cumini (L.) Skeels) Leaves: A Comprehensive Review.

Leaves of jamun collected as agro by-produce during the cultivation of jamun is traditionally used as ayurvedic medicine to treat diabetes, gall bladder stones and other ailments. Most of the beneficial effects of jamun leaves are associated with phytochemicals found in jamun leaves such as gallic acid, tannins, mallic acid, flavonoids, essential oils, jambolin, ellagic acid, jambosine, antimellin and betulinic acid. Jamun possess curative activities like anticancer, antidiabetic, antifertility, anti-inflammatory, antidiarrheal, antimicrobial, antinociceptive, antioxidant, antiradiation, chemotherapeutic, and gastroprotective. The main goal of this review article is to provide information on the nutritional content, phytochemical composition and health promoting properties of jamun leaves. The review of literature based on the phytochemical composition and health promoting benefits of the jamun leaves, suggests that leaves can be used as potential constituent in the formulation of pharmacological drugs. From the review literature it is found that clinical, in-vivo, in-vitro studies are still required to check the health promoting effects of jamun leaves extracts on humans.

Estrogen-mediated mitigation of cardiac oxidative stress in ovariectomized rats is associated with upregulated cardiac circadian clock Per2 and heart-specific miRNAs.

AIM: Estrogen (E2) confers cardioprotection in premenopausal women and in models of menopause and its effects, mostly studied in female reproductive organs, vary on a circadian rhythm basis in relation to the circadian clock genes. However, it remains unknown if a similar circadian pattern exists in the female heart in a manner that explains, at least partly, the cardioprotective effect of E2. The aim of the present investigation was to determine if upregulation of the circadian clock Per2 and its regulated heart-specific miRNAs, and redox enzymes contribute to the E2-mediated cardioprotection in ovariectomized rats. MAIN METHODS: Rats were subjected to ovariectomy (OVX) 2-weeks prior to a 2-week E2 treatment. On the last treatment day, hearts were collected every 4 h. for ex-vivo biochemical measurements. In parallel studies, telemetric mean arterial pressure (MAP) was obtained at the tissue collection times. KEY FINDINGS: OVX + E2 rats exhibited lower body weight during daytime and MAP during day and night times, and their hearts exhibited: (1) higher Per2 protein abundance, cardioprotective miRNAs (miRNA1, miRNA133a, miRNA208a, miRNA499), mALDH2, and catalase; (2) lower reactive oxygen species, cardio-detrimental miRNA652, carbonyl, MDA and HO-1 levels. The reciprocal Per2/HO-1 relationship was more evident during the daytime and correlated with the upregulated cardioprotective miRNAs in OVX + E2 rats. Finally, cardiac Per2, heart-specific miRNAs and reactive oxygen species levels and redox enzymes activities were similar in normal female and OVX + E2 rats. SIGNIFICANCE: Enhancement of cardiac Per2, redox enzymes and heart-specific miRNAs likely contribute to E2-mediated mitigation of cardiac oxidative stress in OVX rats.

Highly proliferative and hypodifferentiated CAR-T cells targeting B7-H3 enhance antitumor activity against ovarian and triple-negative breast cancers.

Chimeric antigen receptor (CAR)-T cell immunotherapy is highly effective against hematological neoplasms. However, owing to tumor variability, low antigen specificity, and impermanent viability of CAR-T cells, their use in the treatment of solid tumors is limited. Here, a novel CAR-T cell targeting B7-H3 and incorporating a 4-1BB costimulatory molecule with STAT3-and STAT5-related activation motifs was constructed using lentivirus transduction. B7-H3, a tumor-associated antigen, and its scFv antibody endowed CAR-T cells with tumor-specific targeting capabilities. Moreover, the integration of the trIL2RB and YRHQ motifs stimulated STAT5 and STAT3 in an antigen-dependent manner, inducing a remarkable increase in the proliferation and survival of CAR-T cells via the activation of the JAK-STAT signaling pathway. Besides, the proportion of less-differentiated T cells increased among BB-trIL2RB-z(YRHQ) CAR-T cells. Moreover, BB-trIL2RB-z(YRHQ) effectively inhibited ovarian cancer (OC) and triple-negative breast cancer (TNBC) in vivo at low doses, without high serum levels of inflammatory cytokines and organ toxicity. Therefore, our study proposes a combination of elements for the construction of superior pluripotent CAR-T cells to provide an effective strategy for the treatment of intractable solid tumors.

Leveraging spatial transcriptomics data to recover cell locations in single-cell RNA-seq with CeLEry.

Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of cellular heterogeneity in health and disease. However, the lack of physical relationships among dissociated cells has limited its applications. To address this issue, we present CeLEry (Cell Location recovEry), a supervised deep learning algorithm that leverages gene expression and spatial location relationships learned from spatial transcriptomics to recover the spatial origins of cells in scRNA-seq. CeLEry has an optional data augmentation procedure via a variational autoencoder, which improves the method's robustness and allows it to overcome noise in scRNA-seq data. We show that CeLEry can infer the spatial origins of cells in scRNA-seq at multiple levels, including 2D location and spatial domain of a cell, while also providing uncertainty estimates for the recovered locations. Our comprehensive benchmarking evaluations on multiple datasets generated from brain and cancer tissues using Visium, MERSCOPE, MERFISH, and Xenium demonstrate that CeLEry can reliably recover the spatial location information for cells using scRNA-seq data.

Binding domain on CD22 molecules contributing to the biological activity of T cell-engaging bispecific antibodies.

CD22, as the B-cell malignancies antigen, has been targeted for immunotherapies through CAR-T cells, antibody-drug conjugates (ADCs) and immunotoxins via interaction of antibodies with binding domains on the receptor. We hypothesized that avidity and binding domain of antibody to target cells may have significant impact on the biological function in tumor immunotherapy, and T cell-engaging bispecific antibody (TCB) targeting CD22 could be used in the therapy of hematologic malignancies. So, to address the question, we utilized the information of six previously reported CD22 mAbs to generate CD22-TCBs with different avidity to different domains on CD22 protein. We found that the avidity of CD22-TCBs to protein was not consistent with the avidity to target cells, indicating that TCBs had different binding mode to the protein and cells. In vitro results indicated that CD22-TCBs mediated cytotoxicity depended on the avidity of antibodies to target cells rather than to protein. Moreover, distal binding domain of the antigen contributed to the avidity and biological activity of IgG-[L]-scfv-like CD22-TCBs. The T cells' proliferation, activation, cytotoxicity as well as cytokine release were compared, and G5/44 BsAb was selected for further in vivo assessment in anti-tumor activity. In vivo results demonstrated that CD22-TCB (G5/44 BsAb) significantly inhibited the tumors growth in mice. All these data suggested that CD22-TCBs could be developed as a promising candidate for B-cell malignancies therapy through optimizing the design with avidity and binding domain to CD22 target in consideration.

Histone Maps in Gossypium darwinii Reveal Epigenetic Regulation Drives Subgenome Divergence and Cotton Domestication.

The functional annotation of genomes, including chromatin modifications, is essential to understand the intricate architecture of chromatin and the consequential gene regulation. However, such an annotation remains limited for cotton genomes. Here, we conducted chromatin profiling in a wild allotetraploid cotton Gossypium darwinii (AD genome) by integrating the data of histone modification, transcriptome, and chromatin accessibility. We revealed that the A subgenome showed a higher level of active histone marks and lower level of repressive histone marks than the D subgenome, which was consistent with the expression bias between the two subgenomes. We show that the bias in transcription and histone modification between the A and D subgenomes may be caused by genes unique to the subgenome but not by homoeologous genes. Moreover, we integrate histone marks and open chromatin to define six chromatin states (S1-S6) across the cotton genome, which index different genomic elements including genes, promoters, and transposons, implying distinct biological functions. In comparison to the domesticated cotton species, we observed that 23.2% of genes in the genome exhibit a transition from one chromatin state to another at their promoter. Strikingly, the S2 (devoid of epigenetic marks) to S3 (enriched for the mark of open chromatin) was the largest transition group. These transitions occurred simultaneously with changes in gene expression, which were significantly associated with several domesticated traits in cotton. Collectively, our study provides a useful epigenetic resource for research on allopolyploid plants. The domestication-induced chromatin dynamics and associated genes identified here will aid epigenetic engineering, improving polyploid crops.

Tea (Camellia sinensis (L.) Kuntze) as an emerging source of protein and bioactive peptides: A narrative review.

Tea residues represent one of the major agricultural wastes that are generated after the processing of tea. They account for 21-28% of crude protein and are often discarded without the extraction of valuable proteins. Due to various bioactivity and functional properties, tea proteins are an excellent alternative to other plant-based proteins for usage as food supplements at a higher dosage. Moreover, their good gelation capacity is ideal for the manufacturing of dairy products, jellies, condensation protein, gelatin gel, bread, etc. The current study is the first to comprehend various tea protein extraction methods and their amino acid profile. The preparation of tea protein bioactive peptides and hydrolysates are summarized. Several functional properties (solubility, foaming capacity, emulsification, water/oil absorption capacity) and bioactivities (antioxidant, antihypertensive, antidiabetic) of tea proteins are emphasized.

Gemcitabine­fucoxanthin combination in human pancreatic cancer cells.

Gemcitabine is a chemotherapeutic agent for pancreatic cancer treatment. It has also been demonstrated to inhibit human pancreatic cancer cell lines, MIA PaCa-2 and PANC-1. The aim of the present study was to investigate the suppressive effect of fucoxanthin, a marine carotenoid, in combination with gemcitabine on pancreatic cancer cells. MTT assays and cell cycle analysis using flow cytometry were performed to study the mechanism of action. The results revealed that combining a low dose of fucoxanthin with gemcitabine enhanced the cell viability of human embryonic kidney cells, 293, while a high dose of fucoxanthin enhanced the inhibitory effect of gemcitabine on the cell viability of this cell line. In addition, the enhanced effect of fucoxanthin on the inhibitory effect of gemcitabine on PANC-1 cells was significant (P<0.01). Fucoxanthin combined with gemcitabine also exerted significant enhancement of the anti-proliferation effect in MIA PaCa-2 cells in a concentration dependent manner (P<0.05), compared with gemcitabine treatment alone. In conclusion, fucoxanthin improved the cytotoxicity of gemcitabine on human pancreatic cancer cells at concentrations that were not cytotoxic to non-cancer cells. Thus, fucoxanthin has the potential to be used as an adjunct in pancreatic cancer treatment.

Antibody-based cancer immunotherapy by targeting regulatory T cells.

Regulatory T cells (Tregs) are among the most abundant suppressive cells, which infiltrate and accumulate in the tumor microenvironment, leading to tumor escape by inducing anergy and immunosuppression. Their presence has been correlated with tumor progression, invasiveness and metastasis. Targeting tumor-associated Tregs is an effective addition to current immunotherapy approaches, but it may also trigger autoimmune diseases. The major limitation of current therapies targeting Tregs in the tumor microenvironment is the lack of selective targets. Tumor-infiltrating Tregs express high levels of cell surface molecules associated with T-cell activation, such as CTLA4, PD-1, LAG3, TIGIT, ICOS, and TNF receptor superfamily members including 4-1BB, OX40, and GITR. Targeting these molecules often attribute to concurrent depletion of antitumor effector T-cell populations. Therefore, novel approaches need to improve the specificity of targeting Tregs in the tumor microenvironment without affecting peripheral Tregs and effector T cells. In this review, we discuss the immunosuppressive mechanisms of tumor-infiltrating Tregs and the status of antibody-based immunotherapies targeting Tregs.