Lumbar lordosis and sacral slope do not differ in two types of postoperative lumbar disc re-herniation: a cross-sectional observational study.

BACKGROUND: To identify the differences of lumbar lordosis (LL) and sacral slope (SS) angles between two types of postoperative lumbar disc re-herniation, including the recurrence of same level and adjacent segment herniation (ASH). METHODS: We searched the medical records of lumbar disc herniation (LDH) patients with re-herniation with complete imaging data (n = 58) from January 1, 2013 to December 30, 2020 in our hospital. After matching for age and sex, 58 patients with LDH without re-herniation from the same period operated by the same treatment group in our hospital were served as a control group. Re-herniation patients were divided into two groups, same-level recurrent lumbar disc herniation group (rLDHG) and adjacent segment herniation group with or without recurrence (ASHG). The preoperative, postoperative and one month after operation LL and SS were measured on standing radiographs and compared with the control group by using t-test, ANOVA, and rank-sum test. Next, we calculated the odds ratios (ORs) by unconditional logistic regression, progressively adjusted for other confounding factors. RESULTS: Compared with the control group, the postoperative LL and SS were significantly lower in LDH patients with re-herniation. However, there were no differences in LL and SS between ASHG and rLDHG at any stage. After progressive adjustment for confounding factors, no matter what stage is, LL and SS remained unassociated with the two types of re-herniation. CONCLUSIONS: Low postoperative LL and SS angles are associated with degeneration of the remaining disc. Low LL and SS may be independent risk factors for re-herniation but cannot determine type of recurrence (same or adjacent disc level).

Azospirillum brasilense activates peroxidase-mediated cell wall modification to inhibit root cell elongation.

The molecular mechanism of beneficial bacterium Azospirillum brasilense-mediated root developmental remain elusive. A. brasilense elicited extensively transcriptional changes but inhibited primary root elongation in Arabidopsis. By analyzing root cell type-specific developmental markers, we demonstrated that A. brasilense affected neither overall organization nor cell division of primary root meristem. The cessation of primary root resulted from reduction of cell elongation, which is probably because of bacterially activated peroxidase that will lead to cell wall cross-linking at consuming of H2O2. The activated peroxidase combined with downregulated cell wall loosening enzymes consequently led to cell wall thickness, whereas inhibiting peroxidase restored root growth under A. brasilense inoculation. We further showed that peroxidase activity was probably promoted by cadaverine secreted by A. brasilense. These results suggest that A. brasilense inhibits root elongation by activating peroxidase and inducing cell wall modification in Arabidopsis, in which cadaverine released by A. brasilense is a potential signal compound.

The role of TGF-ß in the tumor microenvironment of pancreatic cancer.

Pancreatic cancer (PC) is an aggressive malignant tumor with low rate of surgical resection and poor prognosis. Transforming growth factor-ß (TGF-ß) is a cytokine that has both protumor and antitumor activities, depending on tumor microenvironment. The interaction between TGF-ß signaling and the tumor microenvironment in PC is complex. Here, we reviewed the role of TGF-ß in the tumor microenvironment of PC, highlighting producers of TGF-ß and TGF-ß responders in the tumor microenvironment of PC.

Recent development of multi-target VEGFR-2 inhibitors for the cancer therapy.

Vascular epidermal growth factor receptor-2 (VEGFR-2), as an important tyrosine transmembrane protein, plays an important role in regulating endothelial cell proliferation and migration, regulating angiogenesis and other biological functions. VEGFR-2 is aberrantly expressed in many malignant tumors, and it is also related to the occurrence, development, and growth of tumors and drug resistance. Currently, there are nine VEGFR-2 targeted inhibitors approved by US.FDA for clinical use as anticancer drugs. Due to the limited clinical efficacy and potential toxicity of VEGFR inhibitors, it is necessary to develop new strategies to improve the clinical efficacy of VEGFR inhibitors. The development of multitarget therapy, especially dual-target therapy, has become a hot research field of cancer therapy, which may provide an effective strategy with higher therapeutic efficacy, pharmacokinetic advantages and low toxicity. Many groups have reported that the therapeutic effects could be improved by simultaneously inhibiting VEGFR-2 and other targets, such as EGFR, c-Met, BRAF, HDAC, etc. Therefore, VEGFR-2 inhibitors with multi-targeting capabilities have been considered to be promising and effective anticancer agents for cancer therapy. In this work, we reviewed the structure and biological functions of VEGFR-2, and summarized the drug discovery strategies, and inhibitory activities of VEGFR-2 inhibitors with multi-targeting capabilities reported in recent years. This work might provide the reference for the development of VEGFR-2 inhibitors with multi-targeting capabilities as novel anticancer agents.

Cysteine Metabolism in Tumor Redox Homeostasis.

Cysteine (Cys) is a semi-essential nutrient amino acid that plays an important role in cells through endogenous production and various transport systems. Intracellular Cys can be used as a precursor of protein synthesis to maintain cell homeostasis and to generate sulfur-containing substances, including glutathione (GSH), hydrogen sulfide (H2S), and taurine. There have been quite a few reports that Cys is related to tumor occurrence and development, and its level is closely related to tumor proliferation, invasion, and metastasis. Moreover, it helps in maintaining the tumor redox balance and increasing drug resistance. This review aims to summarize the production and metabolism of Cys and its role in tumors, with special emphasis on the potential therapeutic value of Cys in tumors to improve the quality of life of cancer patients.

Autophagy alleviates indium-induced programmed cell death in wheat roots.

Indium released in agroecosystems is becoming an emerging plant stressor, causing cellular damage and consequently crop yield losses. Previous studies have focused on indium-induced toxicity in plants, while plant adaptive responses to such emerging metal xenobiotics are poorly understood. Here, we explored the relationship of autophagy and programmed cell death (PCD) in wheat roots under indium stress. Indium treatment significantly decreased root activity and cell viability, and suppressed the length of root epidermal cells in the elongation zones. These symptoms may be associated with indium-induced PCD, as indium-stressed wheat roots displayed condensed and granular nuclei, increased number of TUNEL-positive nuclei, enhanced nuclear DNA fragmentation and caspase-3-like protease activity compared to untreated roots. Accordingly, indium enhanced the expression levels of TaMCA1 and TaMCA4, two major metacaspase genes mediated PCD in wheat plants. The enhanced expression of autophagy genes and formation of autophagosomes indicate that autophagy could regulate metabolic adaptation and repair stress-induced damage in wheat roots. Furthermore, reinforcing autophagy by activator rapamycin significantly decreased the number of TUNEL-positive nuclei and the activity of caspase-3-like protease, whereas inhibition of autophagy by 3-methyladenine aggravated diagnostic markers for PCD. These results together suggest that autophagy suppresses indium-induced PCD in wheat roots.

Beneficial Bacterium Azospirillum brasilense Induces Morphological, Physiological and Molecular Adaptation to Phosphorus Deficiency in Arabidopsis.

Although most cultivated soils have high levels of total phosphorus (P), the levels of bioavailable inorganic P (Pi) are insufficient. The application of plant-growth-promoting rhizobacteria (PGPR) is an eco-friendly strategy for P utilization; however, PGPR-mediated plant responses that enhance Pi acquisition remain unexplored. Here, we investigated the effect of Azospirillum brasilense on Arabidopsis adaptation to Pi deficiency. Results showed that A. brasilense inoculation alleviated Pi-deficiency-induced growth inhibition and anthocyanin accumulation and increased the total P content in Arabidopsis plants. A comprehensive analysis of root morphology revealed that A. brasilense increased root hair density and length under Pi-limited conditions. We further demonstrated that A. brasilense enhanced the acid phosphatase activity and upregulated the expression of several Pi transporter genes, such as PHOSPHATE1 (PHO1), PHOSPHATE TRANSPORTER 1:(PHT1:1) and PHT1;4. However, A. brasilense did not enhance the growth o total P content in pht1;1, pht1;4 and pht1;1pht1;4 mutants. Moreover, A. brasilense could not increase the P content and PHT1;1 expression in the root hairless mutant rsl4rsl2, because of the occurrence of low-Pi-induced PHT1;1 and PHT1;4 in root hairs. These results indicate that A. brasilense can promote root hair development and enhance acid phosphatase activity and Pi transporter expression levels, consequently improving the Pi absorption capacity and conferring plant tolerance to Pi deficiency.

Short-chain aldehydes increase aluminum retention and sensitivity by enhancing cell wall polysaccharide contents and pectin demethylation in wheat seedlings.

Upon environmental stimuli, aldehydes are generated downstream of reactive oxygen species and thereby contribute to severe cell damage. In this study, using two wheat genotypes differing in aluminum (Al) tolerance, we investigated the effects of lipid peroxidation-derived aldehydes on cell wall composition and subsequent Al-binding capacities. The spatial accumulation of Al along wheat roots was found to the generation of reactive aldehydes, which are highly localized to the apical regions of roots. Elimination of aldehydes by carnosine significantly reduced Al contents in root tips, with a concomitant alleviation of root growth inhibition. In contrast, root growth and Al accumulation were exacerbated by application of the short-chain aldehyde (E)-2-hexenal. We further confirmed that cell wall binding capacity, rather than malate efflux or pH alteration strategies, is associated with the aldehyde-induced accumulation of Al. Scavenging of lipid-derived aldehydes reduced Al accumulation in the pectin and hemicellulose 1 (HC1) fractions of root cell walls, whereas exposure to (E)-2-hexenal promoted a further accumulation of Al, particularly in the cell wall HC1 fraction of the Al-sensitive genotype. Different strategies were introduced by pectin and HC1 to accumulate Al in response to aldehydes in wheat roots. Accumulation in pectin is based on a reduction of methylation levels in response to elevated pectin methylesterase activity and gene expression, whereas that in HC1 is associated with an increase in polysaccharide contents. These findings indicate that aldehydes exacerbate Al phytotoxicity by enhancing Al retention in cell wall polysaccharides.

Indium induces nitro-oxidative stress in roots of wheat (Triticum aestivum).

The entrance of indium, an emerging contaminant from electronics, into the agroecosystem inevitably causes its accumulation in crops and raises exposure risk of humans via food chain. This study investigated indium uptake and toxicological effects in wheat plants under a worst-case scenario. Inhibition of root growth is a primary manifestation of indium toxicity and most absorbed indium accumulated in wheat roots with only a tiny portion reaching the leaves. The enhancement of reactive oxygen species (ROS), lipid peroxidation and protein oxidation in roots suggest that indium caused oxidative stress. Additionally, we found the levels of nitric oxide and peroxyinitrite, two major reactive nitrogen species (RNS), also increased in wheat roots under indium stress. These changes were accompanied by a raise in protein tyrosine nitration, thereby provoking nitrosative stress. The increase in peroxyinitrite and S-nitrosoglutathione content, S-nitrosoglutathione reductase activity as well as a concomitant reduction in glutathione concentrations suggest a rigorous metabolic interplay between ROS and RNS. Moreover, indium simultaneously triggered alteration in protein carbonylation and nitration. Overall, our results suggest that indium induced nitro-oxidative stress which probably contributes to toxicological effects in wheat plants, which are helpful in reducing the potential risk from emerging contaminants analogous to indium to humans.

Alternation of nasopharyngeal microbiota in healthy youth is associated with environmental factors: implication for respiratory diseases.

The nasopharynx is a key niche of the upper respiratory tract which contains many commensal bacteria and potential pathogens. Dysbiosis of the nasopharyngeal (NP) microbiota is associated with a variety of respiratory diseases. Little is known about NP flora in healthy youth, nor about its relationship with environmental factors. We characterized NP microbiota using the 16S rRNA gene sequencing method, and compared microbial composition from subjects sampled in Spring and Fall when exposed to different environmental factors. Results showed that beta diversity was significantly different. Phyla Acidobacteria, Gemmatimonadetes, and genus Symbiobacterium were positively associated with PM2.5. Genera Streptococcus, Prevotella, and [Prevotella] were positively correlated with temperature (T). Ozone (O3) was associated with these floras for exposure that occurred 30 days prior to collection. These preliminary data suggest that the change in environmental factors between spring and fall can influence the composition of the NP microbiota, characterized by a significant correlation to specific taxa. These changes in NP microbiota might be a potential risk factor for respiratory disease.

Lipid Peroxide-Derived Short-Chain Aldehydes are Involved in Aluminum Toxicity of Wheat (Triticum aestivum) Roots.

Lipid peroxidation is a common event during aluminum (Al) toxicity in plants, and it generates an array of aldehyde fragments. The present study investigated and compared the profile and physiological functions of lipid peroxide-derived aldehydes under Al stress in two wheat genotypes that differed in Al resistance. Under Al stress, the sensitive genotype Yangmai-5 suffered more severe plasma membrane damage and accumulated higher levels of aldehydes in roots than the Al-tolerant genotype Jian-864. The complementary use of high-resolution mass spectrometry and standard compounds allowed the identification and quantification of 13 kinds of short-chain aldehydes sourced from lipids in wheat roots. Among these aldehydes, acetaldehyde, isovaldehyde, valeraldehyde, (E)-2-hexenal (HE), heptaldehyde, and nonyl aldehyde were the predominant species. Moreover, it was found that HE in the sensitive genotype was over 2.63 times higher than that in the tolerant genotype after Al treatment. Elimination of aldehydes using carnosine rescued root growth inhibition by 19.59 and 11.63% in Jian-864 and Yangmai-5, respectively, and alleviated Al-induced membrane damage and protein oxidation. Exogenous aldehyde application further inhibited root elongation and exacerbated oxidative injury. The tolerant genotype Jian-864 showed elevated aldehyde detoxifying enzyme activity and transcript levels. These results suggest that lipid peroxide-derived short-chain aldehydes are involved in Al toxicity, and a higher aldehyde-detoxifying capacity may be responsible for Al tolerance.

Revealing the distribution characteristics of antibiotic resistance genes and bacterial communities in animal-aerosol-human in a chicken farm: From One-Health perspective.

Antibiotics in breeding industry can enter the environment through multiple pathways, thus accelerating the emergence and spread of antibiotic resistance genes (ARGs), among which aerosol transmission is easily achieved and often overlooked. To elucidate the role of aerosols in this situation, the present study investigated the distribution characteristics of 107 ARG subtypes (targeting to eight different ARG types) and nine mobile genetic elements (MGEs) and bacterial community in animal (chicken cloaca), environment (aerosols) and human (nasopharynx) of a chicken farm (n = 42) in Henan Province. In total, 116 ARG subtypes and MGEs were identified in the poultry farm. The total bacterial concentration of aerosols inside the chicken house (3.117 × 104 CFU/m3) exceeded the corresponding limit. The microbial communities in the samples of cloaca swab (C) and the workers' nasopharyngeal swab (N) were closer, while the abundance distribution of ARGs/ MGEs in cloacal swab (C) and aerosol (AI) in chicken house were much similar. There were certain consistency of the microbial community structure and the distribution of ARGs among the three groups of chicken cloaca, air aerosol, and workers' nasopharynx. Our results highlighted that animal breeding does have a certain impact on the surrounding environment and human, and aerosols play an important role in this process.

Bacterial composition and community structure of the oropharynx of adults with asthma are associated with environmental factors.

The development and exacerbation of asthma are mainly attributed to inflammatory reactions caused by allergens. However, less is known about the development of asthma caused by microbial disorders in the oropharynx and induced by environmental factors. Here, the metagenome of the oropharyngeal microbiome of adults with asthma was analysed to identify their association with air pollutants. Oropharyngeal swabs from patients with asthma were collected in two winters (W1 and W2) with different environmental factor exposures. The bacterial composition and community structure of the oropharynx were analysed through high-throughput sequencing. After analysis, the α-diversity and ß-diversity exhibited significant differences between the two groups. LEfSe analysis detected 8 significantly different phyla and 11 significantly different genera between the W1 and W2 groups. Multiple linear regression analyses found that the asthma status might contribute to the alteration of microbial composition. Redundancy analysis showed that NO2 was the only environmental factor that significantly affected the microbial community structure of the oropharynx. The different genera associated with NO2 were Rothia, Actinomyces, Fusobacterium and Leptotrichia. The altered taxa related to PM2.5 were Cupriavidus and Acinetobacter. Actinobacillus and Prevotella showed a highly positive correlation with O3. Moreover, network analysis was carried out to explore the co-occurrence relationships of the main genera, and PICRUSt was conducted to predict bacterial functions. This study showed that environmental factors might cause alteration in the oropharyngeal flora, which might be a potential risk factor of asthma.

ATF3 induction following DNA damage is regulated by distinct signaling pathways and over-expression of ATF3 protein suppresses cells growth.

Mammalian cells have a remarkable diverse repertoire of response to genotoxic stress that damage DNA. Cellular responses to DNA damaging agents will initially exhibit gene induction, which is regulated by complex mechanism(s) and probably involves multiple signaling pathways. In this paper, we demonstrate that induction of ATF3 protein, a member of the ATF/CREB family of transcription factors, by ionizing radiation (IR) requires normal cellular p53 function. In contrast, induction of ATF3 after UV radiation (UV) or Methyl methanesulphonate (MMS) is independent of p53 status. Induction of ATF3 by DNA damage is rapid, transient, and through a transcriptional mechanism. The ATF3 promoter is induced by UV and MMS, but not by IR. In addition, ATF3 promoter can be activated by MEKK1, an upstream activator of the ERK and JNK kinase pathway, but not induced following p53 expression. Those results indicate that regulation of ATF3 induction after DNA damage utilizes both the p53-dependent and -independent pathways, and may also involve MAP kinase signaling pathways. Using the tetracycline-inducible system (tet-off), we have found that over-expression of ATF3 protein moderately suppresses cell growth. Interestingly, over-expression of ATF3 protein is able to slow down progression of cells from G1 to S phase, indicating that ATF3 protein might play a negative role in the control of cell cycle progression.

BRCA1 regulates GADD45 through its interactions with the OCT-1 and CAAT motifs.

BRCA1, a breast and ovarian cancer susceptibility gene, has been implicated in gene regulation. Previous studies demonstrate that BRCA1 induces GADD45, a p53-regulated and stress-inducible gene that plays an important role in cellular response to DNA damage. However, the mechanism(s) by which BRCA1 regulates GADD45 remains unclear. In this report, we have shown that BRCA1 activation of the GADD45 promoter is mediated through the OCT-1 and CAAT motifs located at the GADD45 promoter region. Site-directed mutations of both OCT-1 and CAAT motifs abrogate induction of the GADD45 promoter by BRCA1. Both OCT-1 and CAAT motifs are able to confer BRCA1 inducibility in a non-related minimal promoter. Physical associations of BRCA1 protein with transcription factors Oct-1 and NF-YA, which directly bind to the OCT-1 and CAAT motifs, are established by biotin-streptavidin pull-down and coimmunoprecipitation assays. Such protein interactions are required for interaction of BRCA1 with the GADD45 promoter because either immunodepletion of Oct-1 and NF-YA proteins or mutations in the OCT-1 and CAAT motifs disrupt BRCA1 binding to the GADD45 promoter. These findings indicate that BRCA1 can up-regulate its targeted genes through protein-protein interactions and provide a novel mechanism by which BRCA1 participates in transcriptional regulation.