Development and validation of a LASSO prediction model for cisplatin induced nephrotoxicity: a case-control study in China.

BACKGROUND: Early identification of high-risk individuals with cisplatin-induced nephrotoxicity (CIN) is crucial for avoiding CIN and improving prognosis. In this study, we developed and validated a CIN prediction model based on general clinical data, laboratory indications, and genetic features of lung cancer patients before chemotherapy. METHODS: We retrospectively included 696 lung cancer patients using platinum chemotherapy regimens from June 2019 to June 2021 as the traing set to construct a predictive model using Absolute shrinkage and selection operator (LASSO) regression, cross validation, and Akaike's information criterion (AIC) to select important variables. We prospectively selected 283 independent lung cancer patients from July 2021 to December 2022 as the test set to evaluate the model's performance. RESULTS: The prediction model showed good discrimination and calibration, with AUCs of 0.9217 and 0.8288, sensitivity of 79.89% and 45.07%, specificity of 94.48% and 94.81%, in the training and test sets respectively. Clinical decision curve analysis suggested that the model has value for clinical use when the risk threshold ranges between 0.1 and 0.9. Precision-Recall (PR) curve shown in recall interval from 0.5 to 0.75: precision gradually declines with increasing Recall, up to 0.9. CONCLUSIONS: Predictive models based on laboratory and demographic variables can serve as a beneficial complementary tool for identifying high-risk populations with CIN.

A Method for the Synthesis of Thioindoles through Copper-Catalyzed C-S Bond Coupling Reaction.

We herein report the copper-catalyzed C-S bond coupling reaction of indoles with N-thiosuccinimides, resulting in moderate to excellent yields of mono- and bis-sulfenylated compounds such as arylthioindoles, alkylthioindoles, selenylated indoles, and cysteine-substituted indoles. Thioarylation and thioglycosylation at the C2 position of indole alkaloids in the Radix Isatidis were achieved via structural modification. The first total syntheses of isatindigotindolosides III and IV have been successfully carried out. The electrophilic sulfenyl bromides generated in situ can play an important role in the catalytic cycle.

TRPA1 promotes cisplatin-induced acute kidney injury via regulating the endoplasmic reticulum stress-mitochondrial damage.

BACKGROUND: Cisplatin is a widely used and effective chemotherapeutic agent against cancer. However, nephrotoxicity is one of the most common side effects of cisplatin, and it can proceed to acute kidney injury (AKI). Studies have reported that activation of transient receptor potential ankyrin-1 (TRPA1) mediates cisplatin-induced renal tubular cytotoxic injury. The aim of this study was to investigate the mechanism of TRPA1 in promoting cisplatin-induced AKI through modulation of the endoplasmic reticulum stress (ERS)-mitochondrial damage. METHODS: A cisplatin-induced HK-2 cell model in vitro and mouse model in vivo were established. The mechanism of TRPA1 promotes AKI was elucidated by H&E staining, TUNEL staining, transmission electron microscope (TEM), immunofluorescence, CCK-8 viability assays, flow cytometry, Western blotting, JC-1 assay, and enzyme linked immunosorbent assay (ELISA). RESULT: In vivo and in vitro, HC-030031 reduced cisplatin-induced Scr and BUN level elevations; improved cisplatin-induced renal tissue injury, apoptosis, and mitochondrial dysfunction; elevated the reduced ERS-associated proteins glucose-regulated protein 78 (GRP78), glucose-regulated protein 75 (GRP75), and C/EBP homologous protein (CHOP) levels induced by cisplatin; reduced the elevated optic atrophy 1 (OPA1), mito-fusion 1 (MFN1), and mito-fusion 2 (MFN2) protein levels, and elevated phospho-dynamin-related protein 1 (p-DRP1) and mitochondrial fission factor (MFF) protein levels. HC-030031 also reduced the mitochondria-associated endoplasmic reticulum membrane (MAM) structure. In addition, TRPA1 agonists also decreased cell proliferation, increased apoptosis, and triggered mitochondrial dysfunction and calcium overload in HK-2 cells via modulation of MAM. ERS inhibitors and GRP75 inhibitors reversed these changes caused by TRPA1 agonists. CONCLUSION: Our findings suggest that TRPA1 enhances cisplatin-induced AKI via modulation of ERS and mitochondrial damage.

Immunotherapeutic treatment of lung cancer and bone metastasis with a mPLA/mRNA tumor vaccine.

Malignant expansion and rapid metastasis are the main limiting factors to successful treatment of lung cancer. Messenger RNA (mRNA) tumor vaccines are a promising immunotherapeutic treatment for lung cancer as well as other metastatic cancers. Herein, we developed a mPLA/mRNA tumor vaccine (mLPR) to escort mRNA into the cytoplasm and improve immune response with the help of TLR4 agonist mPLA. After nasal administration, the mLPR vaccine stimulated the maturation of dendritic cells, reprogramed M2 macrophages into M1 macrophages, as well cross-activated innate and adaptive immune responses. The mLPR vaccine inhibited the development of lung cancer and reduced bone metastasis by means of immune cell activation, IFN-γ/IL-12 cytokine secretion, and natural killer cell-mediated antibody dependent cellular cytotoxicity. The mPLA/mRNA tumor vaccine will provide ideas and application prospects for the use of mRNA tumor vaccine in the treatment of lung cancer. STATEMENT OF SIGNIFICANCE: Lung cancer and bone metastasis seriously affect patient survival, and traditional treatment methods are inefficient and have many side effects. We have constructed an mRNA vaccine that simultaneously activates the innate immune and adaptive responses of the body, in order to achieve better immunotherapeutic effects. To sum up, we confirmed through vaccine design and in vitro and in vivo immunological studies that the mLPR vaccine stimulated the maturation of dendritic cells, reprogrammed M2 macrophages into M1 macrophages, as well cross activated in vivo and adaptive immune responses.

Characterization of a gE/gI/TK gene-deleted pseudorabies virus variant expressing the Cap protein of porcine circovirus type 2d.

Porcine circovirus type 2 (PCV2) plays a key role in the etiology of PCV2-associated disease (PCVAD), and its predominant strain is PCV2d which is not completely controlled by most commercially available vaccines against PCV2a strains. Pseudorabies (PR) caused by pseudorabies virus (PRV) variants re-emerged in Bartha-K61 vaccine-immunized swine herds in late 2011, which brought considerable losses to the global pig husbandry. Therefore, it is significantly important to develop a safe and effective vaccine against both PCV2d and PRV infection. In the present study, the PCV2d ORF2 gene was amplified by PCR, and cloned into the BamHI site of PRV transfer plasmid pG vector to obtain the recombinant transfer plasmid pG-PCV2dCap-EGFP. Subsequently, it was transfected into ST cells infected with the three gene deleted PRV variant strain NY-gE-/gI-/TK- to generate a recombinant virus rPRV NY-gE-/gI-/TK-/PCV2dCap+/EGFP+, and then the EGFP gene was knocked out to harvest the rPRV NY-gE-/gI-/TK-/PCV2dCap+ using gene-editing technology termed CRISPR/Cas9 system. The recombinant virus rPRV NY-gE-/gI-/TK-/PCV2dCap+ had similar genetic stability and proliferation characteristics to the parental PRV as indicated by PCR and one-step growth curve test, and the expression of Cap was validated by Western blot. In animal experiment, higher PCV2-specific ELISA antibodies and detectable PCV2-specific neutralizing antibodies could be elicited in mice immunized with rPRV NY-gE-/gI-/TK-/PCV2dCap+ compared to commercial PCV2 inactivated vaccine. Moreover, the recombinant virus rPRV NY-gE-/gI-/TK-/PCV2dCap+ significantly reduced the viral loads in the hearts, livers, spleens, lungs, and kidneys in mice following a virulent PCV2d challenge. Mice immunized with rPRV NY-gE-/gI-/TK-/PCV2dCap+ developed comparable PRV-specific humoral immune responses and provided complete protection against a lethal PRV challenge. Together, the rPRV NY-gE-/gI-/TK-/PCV2dCap+ recombinant strain has strong immunogenicity.

eIF3d: A driver of noncanonical cap-dependent translation of specific mRNAs and a trigger of biological/pathological processes.

Eukaryotic initiation factor 3d (eIF3d), a known RNA-binding subunit of the eIF3 complex, is a 66 to 68-kDa protein with an RNA-binding motif and a cap-binding domain. Compared with other eIF3 subunits, eIF3d is relatively understudied. However, recent progress in studying eIF3d has revealed a number of intriguing findings on its role in maintaining eIF3 complex integrity, global protein synthesis, and in biological and pathological processes. It has also been reported that eIF3d has noncanonical functions in regulating translation of a subset of mRNAs by binding to 5'-UTRs or interacting with other proteins independent of the eIF3 complex and additional functions in regulating protein stability. The noncanonical regulation of mRNA translation or protein stability may contribute to the role of eIF3d in biological processes such as metabolic stress adaptation and in disease onset and progression including severe acute respiratory syndrome coronavirus 2 infection, tumorigenesis, and acquired immune deficiency syndrome. In this review, we critically evaluate the recent studies on these aspects of eIF3d and assess prospects in understanding the function of eIF3d in regulating protein synthesis and in biological and pathological processes.

The main battlefield of mRNA vaccine - Tumor immune microenvironment.

With the increasing threat of tumors to humans, mRNA vaccine-based immunotherapy has received extensive attention; however, the killing effect is sometimes unsatisfactory. The occurrence of tumors is closely related to the abnormality of the tumor immune microenvironment, including the increase in the number of immunosuppressive cells, the anomaly of some cells with tumor-killing function, and the increase in the glycolysis pathway, all of which will affect the anti-tumor effect of mRNA vaccines. Furthermore, delivery in the body and successful escape from lysosome are also essential steps that involve the result of killing. Starting from inhibiting tumor growth and metastasis by mRNA vaccines, this paper summarizes the tumor microenvironment constructed by immunosuppressive cells and cytokines, which inhibit immune cells from exerting anti-tumor effects, emphasizing the increase of glycolytic pathway after tumor formation, which makes tumors have a high probability of metastasis. In the present study, mRNA vaccines adjust the number of immune cells by combining adjuvants or immune checkpoint inhibitors (ICIs), thereby improving the tumor immune microenvironment (TIME) and tilting the balance in favor of immune-potent cells can achieve better anti-tumor effects. All efforts to understand the relationship between TIME and mRNA vaccine will provide a basis for tumor treatment in the future.

Combination of a cationic complexes loaded with mRNA and α-Galactose ceramide enhances antitumor immunity and affects the tumor immune microenvironment.

mRNA vaccination is considered to be a promising strategy for tumor immunotherapy. Among, adequate antigen expression and regulation of tumor immune microenvironment are still the key to achieving therapeutic immounotherapy. In oreder to protect mRNA delivered to cells and reverse damaged dendritic cells(DCs), a novel vaccine delivery system composed of an α-Galactose ceramide/cationic liposome complex(α-GC-Lip) was constructed. The α-GC-liposome/protamine/mRNA vaccine complexes(α-GC-LPR) enabled the mRNA to be successfully translated into protein in the cytoplasm of antigen-presenting cells. Further, α-GC-LPR could stimulate dendritic cell maturation via significantly increasing the expression of bone marrow-derived cells(BMDCs) surface molecules and secretion of cytokines to improve the efficacy of immunotherapy. In vivo study, the α-GC-LPR was combined with programmed cell death protein 1(PD-1) inhibitor could activate natural killer cell(NK), T cells as well as significantly reduce the immunosuppression of immune cells, which induced strong antigen-specific immunity in breast cancer model. Our study indicated that the α-GC-LPR combined with immune checkpoint inhibitors as a potential design strategy to effectively enhance the antitumor immune response.

Translation initiation factor eIF3a regulates glucose metabolism and cell proliferation via promoting small GTPase Rheb synthesis and AMPK activation.

Eukaryotic translation initiation factor 3 subunit A (eIF3a), the largest subunit of the eIF3 complex, has been shown to be overexpressed in malignant cancer cells, potentially making it a proto-oncogene. eIF3a overexpression can drive cancer cell proliferation but contributes to better prognosis. While its contribution to prognosis was previously shown to be due to its function in suppressing synthesis of DNA damage repair proteins, it remains unclear how eIF3a regulates cancer cell proliferation. In this study, we show using genetic approaches that eIF3a controls cell proliferation by regulating glucose metabolism via the phosphorylation and activation of AMP-activated protein kinase alpha (AMPKα) at Thr172 in its kinase activation loop. We demonstrate that eIF3a regulates AMPK activation mainly by controlling synthesis of the small GTPase Rheb, largely independent of the well-known AMPK upstream liver kinase B1 and Ca2+/calmodulin-dependent protein kinase kinase 2, and also independent of mammalian target of rapamycin signaling and glucose levels. Our findings suggest that glucose metabolism in and proliferation of cancer cells may be translationally regulated via a novel eIF3a-Rheb-AMPK signaling axis.

eIF3a regulation of mTOR signaling and translational control via HuR in cellular response to DNA damage.

eIF3a (eukaryotic translation initiation factor 3a), a subunit of the eIF3 complex, has been suggested to play a regulatory role in protein synthesis and in cellular response to DNA-damaging treatments. S6K1 is an effector and a mediator of mTOR complex 1 (mTORC1) in regulating protein synthesis and integrating diverse signals into control of cell growth and response to stress. Here, we show that eIF3a regulates S6K1 activity by inhibiting mTORC1 kinase via regulating Raptor synthesis. The regulation of Raptor synthesis is via eIF3a interaction with HuR (human antigen R) and binding of the eIF3a-HuR complex to the 5'-UTR of Raptor mRNA. Furthermore, mTORC1 may mediate eIF3a function in cellular response to cisplatin by regulating synthesis of NER proteins and NER activity. Taken together, we conclude that the mTOR signaling pathway may also be regulated by translational control and mediate eIF3a regulation of cancer cell response to cisplatin by regulating NER protein synthesis.

circCORO1C promotes the proliferation and metastasis of hepatocellular carcinoma by enhancing the expression of PD-L1 through NF-κB pathway.

BACKGROUND: Circular RNA (circRNA) affects the occurrence and development of human cancers, but the specific mechanism of hepatocellular carcinoma (HCC) has not yet been fully understood. METHODS: CircRNAs were determined by human circRNA array analysis and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell viability, migration, invasion, and other indicators were used for cell function analysis. Knockdown and overexpression techniques were used to explore the mechanism of circCORO1C in the occurrence and development of HCC by RNA sequencing, qRT-PCR, western blot, and other methods. RESULTS: Among the thousands of circRNAs, 1238 circRNAs were significantly changed. As for the top 10 upregulated circRNAs, the expression of circRNAs, hsa_circ_0036412, hsa_circ_0036411, hsa_circ_0028071, hsa_circ_0036409, hsa_circ_0000437, hsa_circ_0021427, hsa_circ_0097182, hsa_circ_0028067, hsa_circ_0006852, and hsa_circ_0003620 were significantly increased. In regard to the top 10 downregulated circRNAs, the expression of hsa_circ_0123629, hsa_circ_0096121, hsa_circ_0038932, hsa-circRNA3310-44, hsa_circ_0045746, hsa_circ_0016836, hsa-circRNA10899-9, hsa_circ_0050116, hsa_circ_0035543, and hsa_circ_0092118 decreased significantly. About these circRNAs, the downregulation of hsa_circ_0006852 (circCORO1C) can inhibit the tumorigenesis of HCC cells in vivo and in vitro, and the overexpression of circCORO1C can enhance the proliferation and metastasis ability of HCC cells. Mechanistically, circCORO1C activated the NF-κB signaling pathway, increased P65 phosphorylation and upregulation of c-Myc and COX-2, leading to increased PD-L1 expression. CONCLUSION: CircCORO1C upregulates c-Myc and COX-2 through NF-κB signaling pathway, leading to the upregulation of PD-L1, which jointly promotes the development of HCC, suggesting that circCORO1C is a promising biomarker and therapeutic target for HCC.

CircCNIH4 inhibits gastric cancer progression via regulating DKK2 and FRZB expression and Wnt/ß-catenin pathway.

BACKGROUND: Circular RNAs (circRNAs) have been reported to play an important role in tumor progression in various cancer types, including gastric cancer. The aim of this study was to investigate the role of circCNIH4 (hsa_circ_0000190) in gastric cancer and the underlying mechanism. METHODS: The expression levels of circCNIH4 and Wnt antagonist genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of ß-catenin, Ki67, Dickkopf 2 (DKK2) and Frizzled related protein (FRZB) were measured by western blot. Ectopic overexpression or knockdown of circCNIH4, proliferation, apoptosis, migration and invasion by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry and transwell assay in vitro, and in vivo experiment, were employed to assess the role of circCNIH4 in gastric cancer. RESULTS: CircCNIH4 was downregulated in gastric cancer tissues and cells. Overexpression of circCNIH4 inhibited gastric cancer cell proliferation, migration and invasion and promoted apoptosis by inactivating Wnt/ß-catenin pathway in vitro. CircCNIH4 induced the expression of DKK2 and FRZB in gastric cancer cells. Moreover, silencing of DKK2 or FRZB reversed circCNIH4 overexpression-mediated effects on gastric cancer cells. Additionally, circCNIH4 suppressed tumor growth via regulating DKK2 and FRZB expression in gastric cancer in vivo. CONCLUSION: Our study demonstrated that circCNIH4 played a tumor-inhibiting role through upregulating DKK2 and FRZB expression and suppressing Wnt/ß-catenin pathway in gastric cancer, which might provide a potential biomarker for the diagnosis and treatment of gastric cancer.

Current Perspectives on B Lymphocytes in the Immunobiology of Hepatocellular Carcinoma.

Immune cells infiltrating tumors are capable of significantly impacting carcinogenesis through cancer promotion and anticancer responses. There are many aspects of hepatocellular carcinoma (HCC) related T lymphocytes that are undergoing extensive studies, whereas the effect exerted by B lymphocytes remains a less researched area. In this study, the latest research on the effect of B lymphocytes as they infiltrate tumors in relation to HCC is presented. Their prognosis-related importance is analyzed, along with their function in the tumor microenvironment (TME), as well as the way that B cell biology can be employed to help create a B cell therapy strategy for HCC.

Salidroside and isorhamnetin attenuate urotensin II-induced inflammatory response in vivo and in vitro: Involvement in regulating the RhoA/ROCK II pathway.

Urotensin II (UII), a vital vasoconstrictor peptide, causes an inflammatory response in the pathogenesis of atherosclerosis. Previous studies have reported that the Ras homolog gene family, member A (RhoA)/Rho kinases (ROCK) pathway modulates the inflammatory response of the atherosclerotic process. However, to the best of our knowledge, whether the RhoA/ROCK pathway mediates the inflammatory effect of UII has not been previously elucidated. Salidroside and isorhamnetin are two early developed antioxidant Tibetan drugs, both displaying cardioprotective effects against atherosclerosis. Therefore, the aim of the present study was to investigate the protective effects of salidroside, isorhamnetin or combination of these two drugs on the UII-induced inflammatory response in vivo (rats) or in vitro [primary vascular smooth muscle cells (VSMCs)], as well as to examine the role of the RhoA/ROCK pathway in these processes. The levels of inflammatory markers were measured via ELISA. The mRNA and protein expression levels of RhoA and ROCK II were detected using reverse transcription-quantitative PCR assay and western blot analysis. It was demonstrated that salidroside, isorhamnetin and both in combination decreased the levels of the serum pro-inflammatory cytokines TNF-α and IL-1ß, as well as increased the levels of the anti-inflammatory cytokine IL-10 and macrophage migration inhibitory factor in rats with subacute infusion of UII and in the culture supernatant from primary VSMCs-exposed to UII. Moreover, salidroside, isorhamnetin and both in combination attenuated the mRNA and protein expression levels of RhoA and ROCK II in vivo and in vitro, at concentrations corresponding to human therapeutic blood plasma concentrations. Thus, these drugs could inhibit the RhoA/ROCK II pathway under UII conditions. The combination of salidroside and isorhamnetin did not display a stronger inhibitory effect on the inflammatory response and the RhoA/ROCK II pathway compared with salidroside and isorhamnetin in isolation. Collectively, the results indicated that salidroside, isorhamnetin and both in combination inhibited the RhoA/ROCK II pathway, which then attenuated the inflammatory response under UII-induced conditions, resulting in cardioprotection in atherosclerosis.

TM4SF1, a binding protein of DVL2 in hepatocellular carcinoma, positively regulates beta-catenin/TCF signalling.

The interaction between Axin and DVL2 is critical for the breaking down of the beta-catenin destruction complex and the activation of the Wnt/beta-catenin cascade. However, this biological process remains poorly understood. In the present study, TM4SF1 was identified as the interacting partner of DVL2 and positively regulated as Wnt/beta-catenin signalling by strengthening the DVL2-Axin interaction. The expression levels of TM4SF1 were elevated in hepatocellular carcinoma (HCC) and were induced by Kras signalling. The overexpression of TM4SF1 promoted the growth and motility of HCC cells, and up-regulated the target genes (Axin2 and cyclin D1). The down-regulation of TM4SF1 impaired the capability of HCC cells for growth, migration and metastasis. In addition, the down-regulation of TM4SF1 promoted the ubiquitination of beta-catenin. In summary, these results reveal the oncogenic functions of TM4SF1 in HCC progression and suggest that TM4SF1 might be a target for treatment.

eIF3i regulation of protein synthesis, cell proliferation, cell cycle progression, and tumorigenesis.

eIF3i, a 36-kDa protein, is a putative subunit of the eIF3 complex important for translation initiation of mRNAs. It is a WD40 domain-containing protein with seven WD40 repeats that forms a ß-propeller structure with an important function in pre-initiation complex formation and mRNA translation initiation. In addition to participating in the eIF3 complex formation for global translational control, eIF3i may bind to specific mRNAs and regulate their translation individually. Furthermore, eIF3i has been shown to bind to TGF-ß type II receptor and participate in TGF-ß signaling. It may also participate in and regulate other signaling pathways including Wnt/ß-catenin pathway via translational regulation of COX-2 synthesis. These multiple canonical and noncanonical functions of eIF3i in translational control and in regulating signal transduction pathways may be responsible for its role in cell differentiation, cell cycle regulation, proliferation, and tumorigenesis. In this review, we will critically evaluate recent progresses and assess future prospects in studying eIF3i.

MFAP2 Promotes the Proliferation of Cancer Cells and Is Associated With a Poor Prognosis in Hepatocellular Carcinoma.

BACKGROUNDS: Microfibril-associated protein 2 (MFAP2) is an extracellular matrix protein that regulates the function of microfibrils by interacting with fibrillin. MFAP2 has been reported to play an important role in metabolic diseases and has been shown to be significantly overexpressed in head and neck squamous cell carcinoma and Hepatocellular carcinoma (HCC). However, the molecular function and prognostic value of MFAP2 have never been reported in HCC or other tumors. METHODS: In the present study, expression characteristics of MFAP2 in HCC, its influence on the development of HCC, as well as its function and potential mechanism in HCC were verified by Quantitative reverse transcription-polymerase chain reaction, bioinformatics data mining and in vitro cell experiments. RESULTS: MFAP2 was prominently high-expressed in HCC and associated with cancer stages. HCC patients with higher MFAP2 expression displayed lower overall survival (OS) and disease-specific survival(DSS), while there was no significant difference in recurrence-free survival (RFS). In vitro experiments showed that downregulation of MFAP2 inhibited proliferation, migration level of HCC cells. Transcription factors, DNA methyltransferases, immune factors may interact with MFAP2 mRNA to promote tumor progression in HCC. CONCLUSION: These findings suggest that MFAP2 may play a key role in the development of HCC. Therefore, MFAP2 may be a valuable prognostic marker and an effective anticancer target in HCC.

eIF3a Regulation of NHEJ Repair Protein Synthesis and Cellular Response to Ionizing Radiation.

Translation initiation in protein synthesis regulated by eukaryotic initiation factors (eIFs) is a crucial step in controlling gene expression. eIF3a has been shown to regulate protein synthesis and cellular response to treatments by anticancer agents including cisplatin by regulating nucleotide excision repair. In this study, we tested the hypothesis that eIF3a regulates the synthesis of proteins important for the repair of double-strand DNA breaks induced by ionizing radiation (IR). We found that eIF3a upregulation sensitized cellular response to IR while its downregulation caused resistance to IR. eIF3a increases IR-induced DNA damages and decreases non-homologous end joining (NHEJ) activity by suppressing the synthesis of NHEJ repair proteins. Furthermore, analysis of existing patient database shows that eIF3a expression associates with better overall survival of breast, gastric, lung, and ovarian cancer patients. These findings together suggest that eIF3a plays an important role in cellular response to DNA-damaging treatments by regulating the synthesis of DNA repair proteins and, thus, eIIF3a likely contributes to the outcome of cancer patients treated with DNA-damaging strategies including IR.

Fecal microbiota transplantation therapy for Parkinson's disease: A preliminary study.

Imbalances in the gut microbiota mediate the progression of neurodegenerative diseases such as Parkinson's disease (PD). Fecal microbiota transplantation (FMT) is currently being explored as a potential therapy for PD. The objective of this study was to assess the efficacy and safety of FMT on PD. Fifteen PD patients were included, 10 of them received FMT via colonoscopy (colonic FMT group) and 5 received FMT via nasal-jejunal tube (nasointestinal FMT group). The score of PSQI, HAMD, HAMA, PDQ-39, NMSQ and UPDRS-III significantly decreased after FMT treatment (all P < .05). Colonic FMT group showed significant improvement and longer maintenance of efficacy compared with nasointestinal FMT (P = .002). Two patients achieved self-satisfying outcomes that last for more than 24 months. However, nasointestinal FMT group had no significant therapeutic effect, although UPDRS-III score slightly reduced. There were no patients were satisfied with nasointestinal FMT for more than 3 months. Among 15 PD patients, there were 5 cases had adverse events (AEs), including diarrhea (2 cases), abdominal pain (2 cases) and flatulence (1 case). These AEs were mild and self-limiting. We conclude that FMT can relieve the motor and non-motor symptoms with acceptable safety in PD. Compared with nasointestinal FMT, colonic FMT seems better and preferable.

Accelerating gene function discovery by rapid phenotyping of fatty acid composition and oil content of single transgenic T1 Arabidopsis and camelina seeds.

Arabidopsis is wildly used as a model plant and camelina is increasingly used for oilseed research and applications. Although the Arabidopsis genome has been sequenced for two decades, the functions of many lipid-related genes and their regulators have not been well characterized. Improvements in the efficiency and accuracy of gene investigations are key to effective discovery of gene function and downstream bioengineering of plant oil quantity and quality. In this study, a visible marker was used to quickly identify transgenic T1 seeds and a method has been developed to phenotype fatty acid compositions and oil content of single T1 seeds. A whole seed direct transmethylation method was first optimized with multiple seeds and incubation at 85°C for 2 hours in a transmethylation solvent (5% H2SO4 in methanol with 30% toluene cosolvent) is recommended. Based on this method, a single Arabidopsis seed mini-transmethylation (SAST) method has been established in a 1.5 ml GC sample vial with 200 µl transmethylation solvent. Characteristics of the method were evaluated and it was used to phenotype transgenic T1 seeds expressing AtFAD2 or RcWRI1. Our results indicate that fatty acid composition of T1 individual seeds are consistent with those of pools of multiple seeds from higher generations. However, oil content per individual seed varied substantially and therefore pooling five seeds is recommended for phenotyping oil content of T1 seeds. Additionally, a whole camelina single-seed direct transmethylation was evaluated and results confirm its feasibility. The suitability of partial seed analysis of camelina was investigated but variation in composition of different seed tissues limits this approach.