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1.
Pharmacol Res ; 174: 105971, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34763093

RESUMO

Rosacea is a common chronic inflammatory disease that affects the middle of the face. Due to the unclear pathogenesis, the effective treatment options for rosacea remain limited. In this study, weighted gene co-expression network analyses (WGCNA) identified three rosacea-related hub modules, which were involved in immune-, metabolic- and development- related signaling pathways. Next, the key genes from green and brown modules were submitted to CMap database for drug prediction and metformin was identified as a candidate drug for rosacea. Moreover, network pharmacology analysis identified pharmacological targets of metformin and demonstrated that metformin could help in treating rosacea partly by modulating inflammatory and angiogenesis signaling pathways. Finally, we verified the therapeutic role and mechanism of metformin on rosacea in vivo and vitro. We found that metformin treatment significantly improved rosacea-like skin lesions including immune cells infiltration, cytokines/chemokines expression and angiogenesis. Moreover, metformin suppressed LL37- and TNF-α-induced the ROS production and MAPK-NF-κB signal activation in keratinocytes cells. In conclusion, our findings identified and verified metformin as a novel therapeutic candidate for rosacea, and it alleviates the pathological symptoms, possibly by suppressing inflammatory responses, angiogenesis in rosacea.

2.
Chem Sci ; 12(44): 14855-14862, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34820101

RESUMO

Hepatotoxicity is a serious problem faced by thousands of clinical drugs, and drug-induced liver injury (DILI) caused by chronic administration or overdose has become a major biosafety issue. However, the near-infrared (NIR) fluorescent probes currently used for liver injury detection still suffer from poor liver targeting ability and low sensitivity. Enzyme-activated fluorogenic probes with powerful in situ targeting ability are the key to improving the imaging effect of liver injury. Herein, we rationally designed a leucine aminopeptidase (LAP) activated fluorogenic probe hCy-CA-LAP, which greatly improved the hepatocyte-targeting capability by introducing a cholic acid group. The probe hCy-CA-LAP is converted into a high-emission hCy-CA fluorophore in the presence of LAP, showing high selectivity, high sensitivity and low detection limit (0.0067 U mL-1) for LAP, and successfully realizes the sensitive detection of small fluctuations of LAP in living cells. Moreover, the probe can achieve effective in situ accumulation in the liver, thereby achieving precise imaging and evaluation of two different types of drug-induced hepatotoxicity in vivo. Therefore, the probe hCy-CA-LAP may be a potential tool for exploring the roles of LAP and evaluating the degree of DILI.

3.
J Colloid Interface Sci ; 608(Pt 2): 1162-1172, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34735852

RESUMO

Increasing the electrochemical stability window and working temperature range of supercapacitor aqueous electrolyte is the major task in order to advance aqueous electrolyte-based supercapacitors. Here, a supramolecular induced new electrolyte of lithium bis(trifluoromethanesulfonyl) imide (LiTFSI) in dimethyl sulfoxide (DMSO) and water co-solvent system is proposed. Adjusting the coordination structure among LiTFSI, DMSO, and water in the electrolyte via supramolecular interactions results in its high ionic conductivity, low viscosity, wide electrochemical stability window, and large working temperature range. The new electrolyte-based supercapacitors can work in 2.40 V working potential and 130 °C working-temperature range from -40 to 90 °C. The devices exhibit good electrochemical performances, especially the energy density over 21 Wh kg-1, which is much higher than that with traditional aqueous electrolytes (<10 Wh kg-1). The work paves a way to develop high-performance aqueous electrolytes for supercapacitors.

4.
AMB Express ; 11(1): 153, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34800173

RESUMO

Fowl adenovirus serotype 4 (FAdV-4), the causative agent of hepatitis-hydropericardium syndrome (HHS), distributed widely in the poultry farms in China. Hexon is one of the major capsid proteins associated with viral species or serotypes. However, the epitopes of Hexon protein remain largely unknown. In this study, a monoclonal antibody (mAb) specific to Hexon protein of FAdV-4, designated as 3G8, was generated. Subsequently, the linear peptide recognized by 3G8 was mapped and identified as 213AYGAYVK219 using a series of overlapping peptides generated from Hexon protein. Amino acid sequence analysis revealed that the epitope recognized by 3G8 was highly conserved across all the FAdVs. The epitope was immunogenic and could be recognized by FAdV-4 positive chicken serum samples. These findings will enrich our knowledge regarding the epitope on Hexon and provide valuable information for further characterization of the antigenicity of Hexon protein.

5.
Ann Palliat Med ; 10(9): 9594-9606, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628885

RESUMO

BACKGROUND: ICU-acquired weakness (ICU-AW) is characterized by neuromuscular damage such as limb weakness, yet the cause of ICU-AW remains unclear, which significantly increases the time a patient spends on mechanical ventilation (MV)/in ICU and can even affect a patient's survival rate and quality of life after being discharged. Pulmonary rehabilitation (PR)-related measures can effectively improve the ICU-AW situation, but in the specific implementation actions, many obstacles have been produced, and the treatment effect has been controversial, especially in the application process of mechanically ventilated patients. This study aims to confirm the efficacy of using MV alongside PR for patients with ICU-AW. METHODS: We obtained related randomized controlled trials (RCTs) from Chinese and English databases. All RCTs relevant to the use of PR in ICU-AW patients were retrieved from the following databases from their date of inception through January 31th, 2021: PubMed, EMBASE, The Cochrane Central Register of Controlled Trials, CINAHL, Joanna Briggs Institute (JBI), Web of Science, The Wanfang Database, and CNKI. This literature underwent screening, quality evaluation, and index data extraction by two independent researchers. The evaluation data were meta-analyzed with RevMan 5.3 software (Cochrane, London, UK). RESULTS: In total, we analyzed 15 articles which included 1,710 patients. We found that using PR alongside MV can effectively improve a patient's Medical Research Council (MRC) muscle strength score [mean difference (MD) =4.92, P=0.07], reduce the prevalence of ICU-AW [odds ratio (OR) =0.24, P<0.001], and shorten both MV duration [standardized mean difference (SMD) =-1.50, P<0.001] and ICU stay (SMD =-0.68, P=0.03). DISCUSSION: Implementing PR alongside MV can effectively reduce ICU-AW in patients. However, our standardized cluster PR study still requires further clarification to confirm how various intervention methods can reduce ICU-AW.


Assuntos
Unidades de Terapia Intensiva , Respiração Artificial , Humanos , Londres , Debilidade Muscular , Prevalência
6.
Small ; 17(45): e2104557, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34643326

RESUMO

MnO2 -based material is one of the most promising cathode candidates of aqueous zinc-ion batteries (ZIBs), but its commercialization is hindered by the sluggish reaction kinetics and poor structural stability. Herein, a hierarchical framework consisting of core-shell structured carbon nanotubes@K-birnessite-MnO2 enwrapped by graphene/carbon black bicomponent networks (CNT@KMO@GC) via a simple method for ZIBs is designed and developed. The hierarchical framework characterized with favorable K+ preintercalation, δ-phase, and vertically aligned nanoflake arrays of KMO and 3D electrically conductive network shows the enhanced electronic/ionic conductivity and improved wettability with electrolyte, resulting in the fast charge/mass transport and stable structural stability of CNT@KMO@GC. When used as cathode in ZIBs, CNT@KMO@GC exhibits exciting electrochemical performance with remarkable capacity (405.5 mAh g-1 at 0.30 A g-1 ), high rate performance (166.6 mAh g-1 up to 10.0 A g-1 ), and impressive cycling stability (almost no capacity decay after 2000 cycles and 77.3% retention after 10 000 cycles at 10.0 A g-1 ). The energy storage mechanism of CNT@KMO@GC is clarified as H+ /Zn2+ coinsertion/extraction via electrochemical analysis and ex situ characterization. This study offers an innovative paradigm for the advance of ZIBs.

7.
Front Physiol ; 12: 728208, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489740

RESUMO

Obesity and its related metabolic diseases have become great public health threats worldwide. Although accumulated evidence suggests that circRNA is a new type of non-coding RNAs regulating various physiological and pathological processes, little attention has been paid to the expression profiles and functions of circRNAs in white adipose tissue. In this study, 3,771 circRNAs were detected in three stages of white adipogenesis (preadipocyte, differentiating preadipocyte, and mature adipocyte) by RNA-seq. Experimental validation suggested that the RNA-seq results are highly reliable. We found that nearly 10% of genes which expressed linear RNAs in adipocytes could also generate circRNAs. In addition, 40% of them produced multiple circRNA isoforms. We performed correlation analysis and found that a great deal of circRNAs (nearly 50%) and their parental genes were highly correlated in expression levels. A total of 41 differential expression circRNAs (DECs) were detected during adipogenesis and an extremely high ratio of them (80%) were correlated with their parental genes, indicating these circRNAs may potentially play roles in regulating the expression of their parental genes. KEGG enrichment and GO annotation of the parental genes suggesting that the DECs may participate in several adipogenesis-related pathways. Following rigorous selection, we found that many up-regulated circRNAs contain multiple miRNAs binding sites, such as miR17, miR-30c, and miR-130, indicating they may potentially facilitate their regulatory functions by acting as miRNA sponges. These results suggest that plenty of circRNAs are expressed in white adipogenesis and the DECs may serve as new candidates for future adipogenesis regulation.

8.
Mol Plant ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34530166

RESUMO

Nitrogen is an essential nutrient for plant growth and development, and plays vital roles in crop yield. Assimilation of nitrogen is thus fine-tuned in response to heterogeneous environments. However, the regulatory mechanism underlying this essential process remains largely unknown. Here, we report that a zinc-finger transcription factor, drought and salt tolerance (DST), controls nitrate assimilation in rice by regulating the expression of OsNR1.2. We found that loss of function of DST results in a significant decrease of nitrogen use efficiency (NUE) in the presence of nitrate. Further study revealed that DST is required for full nitrate reductase activity in rice and directly regulates the expression of OsNR1.2, a gene showing sequence similarity to nitrate reductase. Reverse genetics and biochemistry studies revealed that OsNR1.2 encodes an NADH-dependent nitrate reductase that is required for high NUE of rice. Interestingly, the DST-OsNR1.2 regulatory module is involved in the suppression of nitrate assimilation under drought stress, which contributes to drought tolerance. Considering the negative role of DST in stomata closure, as revealed previously, the positive role of DST in nitrogen assimilation suggests a mechanism coupling nitrogen metabolism and stomata movement. The discovery of this coupling mechanism will aid the engineering of drought-tolerant crops with high NUE in the future.

9.
Front Genet ; 12: 719201, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484305

RESUMO

Acupuncture promotes the recovery of neurological function by the overall improvement of ischemic brain injury. It is not only regarded as a rehabilitative treatment but also a pretreatment method for stroke. However, its mechanism has not been fully elucidated. In this study, rats were treated with electroacupuncture (EA) at Baihui (GV20) for 30 min/day for 6 days, ahead of conducting cerebral ischemia-reperfusion (I/R) injury. Infarction volume, Evans blue leakage, and neurological deficits were evaluated at 24 h after I/R injury. Then, the ipsilateral ischemic brain was isolated for RNA sequencing (RNA-Seq) to identify molecular consequences. The results showed that EA pretreatment decreased blood-brain barrier (BBB) permeability, reduced brain infarction volume, and improved neurological outcomes. EA pretreatment could upregulate expression of antivirus and immunity activity-associated genes (such as Ifit1, Ifit3, Irf7, and Oasla) and downregulate expression of matrix disruption-associated genes (Col24a1, Col11a1, Col27a1, etc.) in healthy rats. In addition, it could partially reverse or ameliorate genome-wide transcription changes of the ipsilateral ischemic brain. For the first time, this study provides insight into genomic network modulation of a healthy rat with EA treatment and a EA-preconditioned rat under subsequent I/R injury, which is helpful in explaining acupuncture precondition-induced ischemic tolerance of stroke. It also provides new strategies and targets for the prevention of ischemic stroke.

11.
Sci Adv ; 7(36): eabe8511, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34516921

RESUMO

[Figure: see text].

12.
Insects ; 12(7)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34357289

RESUMO

Henosepilachna vigintioctopunctata (F.) is a serious pest of numerous solanaceous crops in many Asian countries. The purpose of this study was to clarify the effects of delayed mating on mating success, fecundity, fertility, pre-oviposition period, oviposition period, adult longevity, and population life table parameters (including net reproductive rate, intrinsic and finite rates of increase, doubling time, and mean generation time) of H. vigintioctopunctata. Beginning three days after emergence for both sexes, mating was delayed an additional 0, 2, 4, 6, or 8 days. We compared the data when mating was delayed for males only with the data when mating was similarly delayed for females only. Reproductive and life table parameters were calculated from the two data sets and compared. The results showed that the preoviposition and oviposition period of adults was significantly reduced by delayed mating, while the preoviposition period was not significantly different in adults mated at older ages. The mating success rate, fecundity, and proportion of hatching eggs decreased with increasing mating age. Longevity was not affected by the age at mating. Mating delay also affected the life table parameters of H. vigintioctopunctata, with a similar trend observed in the net reproductive rate and intrinsic and finite rates of increase, all of which decreased gradually as the number of delay days increased. The population doubling time increased with increases in mating age. The results also showed that delayed mating was an effective measure to consider in controlling H. vigintioctopunctata. It is hoped that our data will provide a scientific basis and contribute technical guidance for forecasting and integrated management of this pest.

13.
Front Cell Dev Biol ; 9: 652809, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336820

RESUMO

Sperm cells are of unique elongated structure and function, the development of which is tightly regulated by the existing proteins and the posttranslational modifications (PTM) of these proteins. Based on the phylogenetic relationships of various swine breeds, Yorkshire boar is believed to be distinctly different from Duroc boar. The comprehensive differential proteomics and phosphoproteomics profilings were performed on spermatozoa from both Yorkshire and Duroc boars. By both peptide and PTM peptide quantification followed by statistical analyses, 167 differentially expressed proteins were identified from 1,745 proteins, and 283 differentially expressed phosphopeptides corresponding to 102 unique differentially phosphorylated proteins were measured from 1,140 identified phosphopeptides derived from 363 phosphorylated proteins. The representative results were validated by Western blots. Pathway enrichment analyses revealed that majority of differential expression proteins and differential phosphorylation proteins were primarily concerned with spermatogenesis, male gamete generation, sperm motility, energy metabolism, cilium morphogenesis, axonemal dynein complex assembly, sperm-egg recognition, and capacitation. Remarkably, axonemal dynein complex assembly related proteins, such as SMCP, SUN5, ODF1, AKAP3, and AKAP4 that play a key regulatory role in the sperm physiological functions, were significantly higher in Duroc spermatozoa than that of Yorkshire. Furthermore, phosphorylation of sperm-specific proteins, such as CABYR, ROPN1, CALM1, PRKAR2A, and PRKAR1A, participates in regulation of the boar sperm motility mainly through the cAMP/PKA signal pathway in different breeds, demonstrating that protein phosphorylation may be an important mechanism underlying the sperm diversity. Protein-protein interaction analysis revealed that the 14 overlapped proteins between differential expression proteins and differential phosphorylation proteins potentially played a key role in sperm development and motility of the flagellum, including the proteins ODF1, SMCP, AKAP4, FSIP2, and SUN5. Taken together, these physiologically and functionally differentially expressed proteins (DEPs) and differentially expressed phosphorylated proteins (DPPs) may constitute the proteomic backgrounds between the two different boar breeds. The validation will be performed to delineate the roles of these PTM proteins as modulators of Yorkshire and Duroc boar spermatozoa.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34394380

RESUMO

Aim: Based on the bibliometric method, the toxicity of aconite is analyzed and evaluated. Methods: Studies on the toxicity of aconite were retrieved from CNKI, CQVIP, Chinese Biomedical Literature Service System, and PubMed, ranging from January 1985 to November 2020. All those studies were formed into the Database of Literature of Toxicity of Aconite (DLTA). Studies on the toxicity of aconite were retrieved from CNKI, CQVIP, SinoMed, and PubMed, respectively. Collecting relevant information in DLTA, we analyzed the hotspots, factors and mechanism of aconite toxicity, and attenuation methods. Results: A total of 445 studies on the toxicity of aconite have been collected. "Compatibility attenuation" and "Processing attenuation" have been the hotspots of aconite toxicity in recent years. Many studies support that the main toxic reactions of aconite are heart damage, liver toxicity, nephrotoxicity, and neurotoxicity. The toxic effect of aconite is related to the effect on the central nervous system. Exciting the vagus nerve reduces the autonomy of the sinus node and damages myocardial cells. The decoction time, dosage, and administration of aconite are the main factors of the toxicity of aconite. There are few studies about the effect of the origin of aconite and the specifications of the medicinal materials on toxicity. Therefore, it is impossible to analyze its relevance. At present, the commonly used methods to reduce the toxicity of aconite mainly include three methods: drug compatibility, processing, and decoction. The most common compatibility with aconite medicines includes licorice, dried ginger, ginseng, and ephedra. Black sliced aconite, steamed slices, and fried slices are less toxic than other processed products. Aconite decoction for more than 60 minutes can basically reach the safe range, and more than 2 hours of decoction may cause the loss of active ingredients. Conclusions: The research on the mechanisms of aconite dosage-efficacy-toxicity, compatibility, processing, liver toxicity, and nephrotoxicity is still not comprehensive and in-depth. Researchers should perfect toxicity studies of aconite, remove the constraints that affect its clinical application, and promote the clinical use of aconite safely and reasonably.

15.
Animals (Basel) ; 11(6)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199180

RESUMO

Cathepsin S (CTSS) is a member of cysteine protease family. Although many studies have demonstrated the vital role of CTSS in many physiological and pathological processes including tumor growth, angiogenesis and metastasis, the function of CTSS in the development of rabbit granulosa cells (GCS) remains unknown. To address this question, we isolated rabbit GCS and explored the regulatory function of the CTSS gene in cell proliferation and apoptosis. CTSS overexpression significantly promoted the secretion of progesterone (P4) and estrogen (E2) by increasing the expression of STAR and CYP19A1 (p < 0.05). We also found that overexpression of CTSS increased GCS proliferation by up-regulating the expression of proliferation related gene (PCNA) and anti-apoptotic gene (BCL2). Cell apoptosis was markedly decreased by CTSS activation (p < 0.05). In contrast, CTSS knockdown significantly decreased the secretion of P4 and E2 and the proliferation of rabbit GCS, while increasing the apoptosis of rabbit GCS. Taken together, our results highlight the important role of CTSS in regulating hormone secretion, cell proliferation, and apoptosis in rabbit GCS. These results might provide a basis for better understanding the molecular mechanism of rabbit reproduction.

16.
Nano Lett ; 21(14): 6005-6013, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34242035

RESUMO

Nanomaterial-biology interaction is the critical step in the fate of biomedical nanomedicines, influencing the consequent biological outcomes. Herein, we present two-dimensional carbon-based nanomaterials-graphdiyne oxide (GDYO) nanosheets that interact with an intracellular protein corona consisting of signal transducer and activator of transcription 3 (STAT3), inducing the reeducation of immunosuppressive macrophages. The interaction at the GDYO-STAT3 interface, driven by structure matching, hydrogen bonding, and salt bridges, simultaneously triggers the immune response in the tumor microenvironment, facilitating cancer immunotherapy. For the first time, our data reveal an interaction mechanism between the nanoparticle-protein interfaces inevitably formed inside the cells that determines the macrophage phenotype. Our results suggest that GDYO nanosheets could be applied for local immunomodulation due to their function and structural organization of the intracellular protein corona occurred inside macrophages.


Assuntos
Coroa de Proteína , Grafite , Imunidade , Imunomodulação , Óxidos
17.
J Immunother Cancer ; 9(7)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34244308

RESUMO

BACKGROUND: Neoantigen (NeoAg) peptides displayed at the tumor cell surface by human leukocyte antigen molecules show exquisite tumor specificity and can elicit T cell mediated tumor rejection. However, few NeoAgs are predicted to be shared between patients, and none to date have demonstrated therapeutic value in the context of vaccination. METHODS: We report here a phase I trial of personalized NeoAg peptide vaccination (PPV) of 24 stage III/IV non-small cell lung cancer (NSCLC) patients who had previously progressed following multiple conventional therapies, including surgery, radiation, chemotherapy, and tyrosine kinase inhibitors (TKIs). Primary endpoints of the trial evaluated feasibility, tolerability, and safety of the personalized vaccination approach, and secondary trial endpoints assessed tumor-specific immune reactivity and clinical responses. Of the 16 patients with epidermal growth factor receptor (EGFR) mutations, nine continued TKI therapy concurrent with PPV and seven patients received PPV alone. RESULTS: Out of 29 patients enrolled in the trial, 24 were immunized with personalized NeoAg peptides. Aside from transient rash, fatigue and/or fever observed in three patients, no other treatment-related adverse events were observed. Median progression-free survival and overall survival of the 24 vaccinated patients were 6.0 and 8.9 months, respectively. Within 3-4 months following initiation of PPV, seven RECIST-based objective clinical responses including one complete response were observed. Notably, all seven clinical responders had EGFR-mutated tumors, including four patients that had continued TKI therapy concurrently with PPV. Immune monitoring showed that five of the seven responding patients demonstrated vaccine-induced T cell responses against EGFR NeoAg peptides. Furthermore, two highly shared EGFR mutations (L858R and T790M) were shown to be immunogenic in four of the responding patients, all of whom demonstrated increases in peripheral blood neoantigen-specific CD8+ T cell frequencies during the course of PPV. CONCLUSIONS: These results show that personalized NeoAg vaccination is feasible and safe for advanced-stage NSCLC patients. The clinical and immune responses observed following PPV suggest that EGFR mutations constitute shared, immunogenic neoantigens with promising immunotherapeutic potential for large subsets of NSCLC patients. Furthermore, PPV with concurrent EGFR inhibitor therapy was well tolerated and may have contributed to the induction of PPV-induced T cell responses.

18.
Acta Derm Venereol ; 101(6): adv00488, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34159391

RESUMO

The exact mechanisms of rosacea development are unknown, but it has been suggested that tea consumption may be associated with its development. To determine the relationship between tea drinking behaviour and rosacea, this clinical case-control study recruited 2,063 participants, who completed a questionnaire about tea drinking behaviour. A 1:1 ratio propensity score matching method was used to generate 619 cases and 619 controls. High-frequency tea drinking (3 times/day: adjusted odds ratio (aOR) 2.592; 95% confidence interval (95% CI) 1.225-5.485; ≥ 4 times/day; aOR 8.86; 95% CI 3.43-22.887), non-fermented tea (aOR 2.172; 95% CI 1.562-3.022), and hot tea (aOR 2.793; 95% CI 1.796-1.344) were associated with an increased risk of rosacea. Further results showed that these tea drinking behaviours were significantly associated with an increased risk of flushing (aOR 1.41; 95% CI 1.07-1.87) and erythema (aOR 1.48; 95% CI 1.10-2.00). Tea drinking behaviour is closely related to rosacea and.


Assuntos
Rosácea , Chá , Estudos de Casos e Controles , Humanos , Razão de Chances , Fatores de Risco , Rosácea/diagnóstico , Rosácea/epidemiologia
19.
Am J Cancer Res ; 11(5): 2159-2173, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34094675

RESUMO

MiR-22 has been demonstrated to inhibits tumor growth in several cancers. However, its function in the tumor microenvironment is still unclear, especially for T cell differentiation. Here, miR-22 expression in the circulating T cells from hepatocellular carcinoma (HCC) patients and healthy controls was analyzed with quantitative polymerase chain reaction (qPCR). Diethylnitrosamine (DEN)/phenobarbital (PB)-mediated primary HCC and Hepa1-6 subcutaneous tumor mouse models were established and subjected to lenti-miR-22 injection. Mice immunoreconstituted with miR-22-overexpressing T cells were employed to investigate the antitumor effect of miR-22 in mice. Luciferase assay, immunofluorescent staining, in vitro Th17 cell differentiation assay, and rescue experiments were employed to investigate the mechanism underlying the miR-22-mediated regulation of Th17 cell differentiation and liver tumor growth. Results confirmed the dramatic downregulation of miR-22 expression in malignant tissues and circulating T cells from patients with HCC. MiR-22 expression correlated with good prognosis of patients. Overexpression of miR-22 impaired the DEN/PB-induced primary HCC formation and the growth of Hepa1-6 subcutaneous tumors by promoting Th17 differentiation. Injection of miR-22-overexpressing T cells in irradiated mice resulted in the inhibition of Hepa1-6 subcutaneous tumor growth via Th17 differentiation promotion. MiR-22 could directly bind to Jarid2, which played an important role during the miR-22-mediated regulation of Th17 differentiation. Taken together, our study expands the understanding of miR-22 function and provides a therapy target for HCC.

20.
Mol Plant ; 14(9): 1539-1553, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34102336

RESUMO

Although roots are mainly embedded in the soil, recent studies revealed that light regulates mineral nutrient uptake by roots. However, it remains unclear whether the change in root system architecture in response to different rhizosphere nutrient statuses involves light signaling. Here, we report that blue light regulates primary root growth inhibition under phosphate-deficient conditions through the cryptochromes and their downstream signaling factors. We showed that the inhibition of root elongation by low phosphate requires blue light signal perception at the shoot and transduction to the root. In this process, SPA1 and COP1 play a negative role while HY5 plays a positive role. Further experiments revealed that HY5 is able to migrate from the shoot to root and that the shoot-derived HY5 autoactivates root HY5 and regulates primary root growth by directly activating the expression of LPR1, a suppressor of root growth under phosphate starvation. Taken together, our study reveals a regulatory mechanism by which blue light signaling regulates phosphate deficiency-induced primary root growth inhibition, providing new insights into the crosstalk between light and nutrient signaling.

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