CCDC92 promotes podocyte injury by regulating PA28α/ABCA1/cholesterol efflux axis in type 2 diabetic mice.

Podocyte lipotoxicity mediated by impaired cellular cholesterol efflux plays a crucial role in the development of diabetic kidney disease (DKD), and the identification of potential therapeutic targets that regulate podocyte cholesterol homeostasis has clinical significance. Coiled-coil domain containing 92 (CCDC92) is a novel molecule related to metabolic disorders and insulin resistance. However, whether the expression level of CCDC92 is changed in kidney parenchymal cells and the role of CCDC92 in podocytes remain unclear. In this study, we found that Ccdc92 was significantly induced in glomeruli from type 2 diabetic mice, especially in podocytes. Importantly, upregulation of Ccdc92 in glomeruli was positively correlated with an increased urine albumin-to-creatinine ratio (UACR) and podocyte loss. Functionally, podocyte-specific deletion of Ccdc92 attenuated proteinuria, glomerular expansion and podocyte injury in mice with DKD. We further demonstrated that Ccdc92 contributed to lipid accumulation by inhibiting cholesterol efflux, finally promoting podocyte injury. Mechanistically, Ccdc92 promoted the degradation of ABCA1 by regulating PA28α-mediated proteasome activity and then reduced cholesterol efflux. Thus, our studies indicate that Ccdc92 contributes to podocyte injury by regulating the PA28α/ABCA1/cholesterol efflux axis in DKD.

Recent advances in radical-mediated intermolecular (4 + 2) cycloaddition.

(4 + 2) Cycloaddition plays an important role in the synthesis of versatile carbocyclic/heterocyclic compounds with its high atom- and step-economy. Additionally, with mild conditions and indispensable functional group compatibility, the radical reaction has been recognized as a useful tool in organic chemistry. Given the enormous impact of radical-mediated (4 + 2) cycloaddition processes and their promising applications, we summarize and highlight the recent works in this attractive area. On the basis of the types of radicals that initiate different (4 + 2) cycloaddition processes, we classify them into processes involving alkenyl cations or alkenyl radicals, aryl radicals, acyl radicals, alkyl radicals, and heteroatom radicals, and this review places special emphasis on the reaction design and mechanisms, which will stimulate future developments in radical-mediated intermolecular (4 + 2) cycloaddition.

ß-arrestin2 deficiency ameliorates S-100-induced autoimmune hepatitis in mice by inhibiting infiltration of monocyte-derived macrophage and attenuating hepatocyte apoptosis.

Autoimmune hepatitis (AIH) is a progressive hepatitis syndrome characterized by high transaminase levels, interface hepatitis, hypergammaglobulinemia, and the presence of autoantibodies. Misdiagnosis or delayed treatment of AIH can lead to cirrhosis or liver failure, which poses a major risk to human health. ß-Arrestin2, a key scaffold protein for intracellular signaling pathways, has been found to be involved in many autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. However, whether ß-arrestin2 plays a role in AIH remains unknown. In the present study, S-100-induced AIH was established in both wild-type mice and ß-arrestin2 knockout (Arrb2 KO) mice, and the experiments identified that liver ß-arrestin2 expression was gradually increased, and positively correlated to serum ANA, ALT and AST levels during AIH progression. Furthermore, ß-arrestin2 deficiency ameliorated hepatic pathological damage, decreased serum autoantibody and inflammatory cytokine levels. ß-arrestin2 deficiency also inhibited hepatocyte apoptosis and prevented the infiltration of monocyte-derived macrophages into the damaged liver. In vitro experiments revealed that ß-arrestin2 knockdown suppressed the migration and differentiation of THP-1 cells, whereas ß-arrestin2 overexpression promoted the migration of THP-1 cells, which was regulated by the activation of the ERK and p38 MAPK pathways. In addition, ß-arrestin2 deficiency attenuated TNF-α-induced primary hepatocyte apoptosis by activating the Akt/GSK-3ß pathway. These results suggest that ß-arrestin2 deficiency ameliorates AIH by inhibiting the migration and differentiation of monocytes, decreasing the infiltration of monocyte-derived macrophages into the liver, thereby reducing inflammatory cytokines-induced hepatocytes apoptosis. Therefore, ß-arrestin2 may act as an effective therapeutic target for AIH.

GPR97 deficiency ameliorates renal interstitial fibrosis in mouse hypertensive nephropathy.

Hypertensive nephropathy (HTN) ranks as the second-leading cause of end-stage renal disease (ESRD). Accumulating evidence suggests that persistent hypertension injures tubular cells, leading to tubulointerstitial fibrosis (TIF), which is involved in the pathogenesis of HTN. G protein-coupled receptors (GPCRs) are implicated in many important pathological and physiological processes and act as important drug targets. In this study, we explored the intrarenal mechanisms underlying hypertension-associated TIF, and particularly, the potential role of GPR97, a member of the adhesion GPCR subfamily, in TIF. A deoxycorticosterone acetate (DOCA)/salt-induced hypertensive mouse model was used. We revealed a significantly upregulated expression of GPR97 in the kidneys, especially in renal tubules, of the hypertensive mice and 10 patients with biopsy-proven hypertensive kidney injury. GPR97-/- mice showed markedly elevated blood pressure, which was comparable to that of wild-type mice following DOCA/salt treatment, but dramatically ameliorated renal injury and TIF. In NRK-52E cells, we demonstrated that knockdown of GPR97 suppressed the activation of TGF-ß signaling by disturbing small GTPase RhoA-mediated cytoskeletal reorganization, thus inhibiting clathrin-mediated endocytosis of TGF-ß receptors and subsequent Smad activation. Collectively, this study demonstrates that GPR97 contributes to hypertension-associated TIF at least in part by facilitating TGF-ß signaling, suggesting that GPR97 is a pivotal intrarenal factor for TIF progression under hypertensive conditions, and therapeutic strategies targeting GPR97 may improve the outcomes of patients with HTN.

TFEB, a master regulator of autophagy and biogenesis, unexpectedly promotes apoptosis in response to the cyclopentenone prostaglandin 15d-PGJ2.

Transcriptional factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis, is generally regarded as a pro-survival factor. Here, we identify that besides its effect on autophagy induction, TFEB exerts a pro-apoptotic effect in response to the cyclopentenone prostaglandin 15-deoxy-∆-12,14-prostaglandin J2 (15d-PGJ2). Specifically, 15d-PGJ2 promotes TFEB translocation from the cytoplasm into the nucleus to induce autophagy and lysosome biogenesis via reactive oxygen species (ROS) production rather than mTORC1 inactivation. Surprisingly, TFEB promotes rather than inhibits apoptosis in response to 15d-PGJ2. Mechanistically, ROS-mediated TFEB translocation into the nucleus transcriptionally upregulates the expression of ATF4, which is required for apoptosis elicited by 15d-PGJ2. Additionally, inhibition of TFEB activation by ROS scavenger N-acetyl cysteine or inhibition of protein synthesis by cycloheximide effectively compromises ATF4 upregulation and apoptosis in response to 15d-PGJ2. Collectively, these results indicate that ROS-induced TFEB activation exerts a novel role in promoting apoptosis besides its role in regulating autophagy in response to 15d-PGJ2. This work not only evidences how TFEB is activated by 15d-PGJ2, but also unveils a previously unexplored role of ROS-dependent activation of TFEB in modulating cell apoptosis in response to 15d-PGJ2.

Lemairamin, isolated from the Zanthoxylum plants, alleviates pain hypersensitivity via spinal α7 nicotinic acetylcholine receptors.

Lemairamin (also known as wgx-50), is isolated from the pericarps of the Zanthoxylum plants. As an agonist of α7 nicotinic acetylcholine receptors (α7nAChRs), it can reduce neuroinflammation in Alzheimer's disease. This study evaluated its antinociceptive effects in pain hypersensitivity and explored the underlying mechanisms. The data showed that subcutaneous lemairamin injection dose-dependently inhibited formalin-induced tonic pain but not acute nociception in mice and rats, while intrathecal lemairamin injection also dose-dependently produced mechanical antiallodynia in the ipsilateral hindpaws of neuropathic and bone cancer pain rats without affecting mechanical thresholds in the contralateral hindpaws. Multiple bi-daily lemairamin injections for 7 days did not induce mechanical antiallodynic tolerance in neuropathic rats. Moreover, the antinociceptive effects of lemairamin in formalin-induced tonic pain and mechanical antiallodynia in neuropathic pain were suppressed by the α7nAChR antagonist methyllycaconitine. In an α7nAChR antagonist-reversible manner, intrathecal lemairamin also stimulated spinal expression of IL-10 and ß-endorphin, while lemairamin treatment induced IL-10 and ß-endorphin expression in primary spinal microglial cells. In addition, intrathecal injection of a microglial activation inhibitor minocycline, anti-IL-10 antibody, anti-ß-endorphin antiserum or µ-opioid receptor-preferred antagonist naloxone was all able to block lemairamin-induced mechanical antiallodynia in neuropathic pain. These data demonstrated that lemairamin could produce antinociception in pain hypersensitivity through the spinal IL-10/ß-endorphin pathway following α7nAChR activation.

The spinal microglial IL-10/ß-endorphin pathway accounts for cinobufagin-induced mechanical antiallodynia in bone cancer pain following activation of α7-nicotinic acetylcholine receptors.

BACKGROUND: Cinobufagin is the major bufadienolide of Bufonis venenum (Chansu), which has been traditionally used for the treatment of chronic pain especially cancer pain. The current study aimed to evaluate its antinociceptive effects in bone cancer pain and explore the underlying mechanisms. METHODS: Rat bone cancer model was used in this study. The withdrawal threshold evoked by stimulation of the hindpaw was determined using a 2290 CE electrical von Frey hair. The ß-endorphin and IL-10 levels were measured in the spinal cord and cultured primary microglia, astrocytes, and neurons. RESULTS: Cinobufagin, given intrathecally, dose-dependently attenuated mechanical allodynia in bone cancer pain rats, with the projected Emax of 90% MPE and ED50 of 6.4 µg. Intrathecal cinobufagin also stimulated the gene and protein expression of IL-10 and ß-endorphin (but not dynorphin A) in the spinal cords of bone cancer pain rats. In addition, treatment with cinobufagin in cultured primary spinal microglia but not astrocytes or neurons stimulated the mRNA and protein expression of IL-10 and ß-endorphin, which was prevented by the pretreatment with the IL-10 antibody but not ß-endorphin antiserum. Furthermore, spinal cinobufagin-induced mechanical antiallodynia was inhibited by the pretreatment with intrathecal injection of the microglial inhibitor minocycline, IL-10 antibody, ß-endorphin antiserum and specific µ-opioid receptor antagonist CTAP. Lastly, cinobufagin- and the specific α-7 nicotinic acetylcholine receptor (α7-nAChR) agonist PHA-543613-induced microglial gene expression of IL-10/ß-endorphin and mechanical antiallodynia in bone cancer pain were blocked by the pretreatment with the specific α7-nAChR antagonist methyllycaconitine. CONCLUSIONS: Our results illustrate that cinobufagin produces mechanical antiallodynia in bone cancer pain through spinal microglial expression of IL-10 and subsequent ß-endorphin following activation of α7-nAChRs. Our results also highlight the broad significance of the recently uncovered spinal microglial IL-10/ß-endorphin pathway in antinociception.

Effects of UV-B radiation on the survival, egg hatchability and transcript expression of antioxidant enzymes in a high-temperature adapted strain of Neoseiulus barkeri.

Biological control of spider mites in hot and dry weather is a serious technical issue. A high-temperature adapted strain (HTAS) of the predatory mite Neoseiulus barkeri Hughes was selected from its conventional strain (CS), via long-term heat acclimation and frequent heat hardenings in our previous studies. However, the environment of high temperature is usually associated with enhanced ultraviolet (UV) radiation. In the present study, the physiological effects of UV-B radiation on survival rate and egg damage of N. barkeri were investigated, as well as the activities and expression profiles of antioxidant enzymes to UV-B radiation stress. UV-B radiation had deleterious effects on egg hatchability and survival of N. barkeri. Adults of the HTAS strain were less UV-B resistant than those of the CS strain; they also had lower levels of enzymatic activity of superoxide dismutase (SOD) and catalase against oxidative damage and weaker upregulation of SOD genes. The mRNA expression of three SOD genes of CS adult females immediately increased whereas that of HTAS showed almost no difference under UV-B stress for 1 h. The results showed the HTAS of N. barkeri had lower fitness under UV-B stress compared with the CS of N. barkeri. These results suggested that long-term heat acclimation may exert a profound impact on the developmental physiology of N. barkeri.

Chitosan elicitation of Isatis tinctoria L. hairy root cultures for enhancing flavonoid productivity and gene expression and related antioxidant activity.

Elicitation for phytochemical enhancement via cost-effective elicitors can overcome the limitation of commercial application faced by plant cell and organ culture technology. Chitosan is a natural, low-cost, and nontoxic elicitor that can trigger plant defense responses with the concomitant enhancement in phytochemical biosynthesis. In this work, the elicitation of Isatis tinctoria L. hairy root cultures by chitosan was conducted to enhance the production of pharmacologically active flavonoids. In comparison with control (2.31 ±â€¯0.29 mg/g DW), a 7.08-fold enhancement of total flavonoids (16.35 ±â€¯0.88 mg/g DW) was achieved in 24 day-old I. tinctoria hairy root cultures elicited by 150 mg/L chitosan for 36 h. Interestingly, the multiple hydroxyl-substituted flavonoids (rutin, quercetin, isorhamnetin, and isoliquiritigenin) were noticed to increase significantly in chitosan-elicited I. tinctoria hairy root cultures. Moreover, the transcription of associated genes involved in flavonoid biosynthesis pathway was significantly up-regulated underlying chitosan elicitation, among which chalcone synthase and flavonoid 3'-hydroxylase might play an important role in flavonoid enhancement. Additionally, extracts from chitosan-elicited I. tinctoria hairy root cultures exhibited higher antioxidant activities with lower IC50 values as compared with control. Overall, a cost-effective strategy via the simple chitosan elicitation is provided here to enhance the production of high-added value flavonoids in I. tinctoria hairy root cultures, which paves the way toward the successful commercialization of this in vitro culture system in the future.

Neuroprotective Natural Products for the Treatment of Parkinson's Disease by Targeting the Autophagy-Lysosome Pathway: A Systematic Review.

The autophagy-lysosome pathway (ALP) is a primary means by which damaged organelles and long-lived proteins are removed from cells and their components recycled. Impairment of the ALP has been found to be linked to the pathogenesis of Parkinson's disease (PD), a chronic neurodegenerative disorder characterized by the accumulation of protein aggregates and loss of dopaminergic neurons in the midbrain. In recent years, some active compounds derived from plants have been found to regulate the ALP and to exert neuroprotective effects in experimental models of PD, raising the possibility that autophagy enhancement may be an effective therapeutic strategy in PD treatment. In this review, we summarize recent findings of natural products that enhance ALP and thereby protect against PD. Research articles were retrieved from PubMed using relevant keywords in combination. Papers related to the topic were identified, and then the reliability of the experiments was assessed in terms of methodology. The results suggest that targeting the ALP with natural products is a promising strategy for PD treatment. However, risk of bias exists in some studies due to the defective methodology. Rigorous experimental design following the guidelines of autophagy assays, molecular target identification and in vivo efficacy evaluation is critical for the development of ALP enhancers for PD treatment in future studies. Copyright © 2017 John Wiley & Sons, Ltd.

Neurogenic Traditional Chinese Medicine as a Promising Strategy for the Treatment of Alzheimer's Disease.

Hippocampal neurogenesis plays a critical role in the formation of new neurons during learning and memory development. Attenuation of neurogenesis in the brain is one of the primary causes of dementia in Alzheimer's disease (AD), and, conversely, modulating the process of hippocampal neurogenesis benefit patients with AD. Traditional Chinese medicine (TCM), particularly herbal medicine, has been in use for thousands of years in Asia and many regions of the world for the treatment of cancer, cardiovascular diseases and neurodegenerative diseases. In this review, we summarize the role of neurotrophic factors, signal transducing factors, epigenetic modulators and neurotransmitters in neurogenesis, and we also discuss the functions of several Chinese herbs and their active molecules in activating multiple pathways involved in neurogenesis. TCM herbs target pathways such as Notch, Wnt, Sonic Hedgehog and receptor tyrosine kinase pathway, leading to activation of a signaling cascade that ultimately enhances the transcription of several important genes necessary for neurogenesis. Given these pathway activating effects, the use of TCM herbs could be an effective therapeutic strategy for the treatment of AD.

Feather mites of the genus Passeroptes Fain (Acariformes: Dermationidae) from passerines (Aves: Passeriformes) of China.

Five new species of the feather mite genus Passeroptes (Acariformes: Dermationidae) are recorded from birds of the order Passeriformes in China: P. lioparis sp. nov. from Chrysotus chrysotis (Blyth) (Paradoxornithidae); P. motacillae sp. nov. from Motacilla cinerea Tunstall (Motacillidae); P. cyanodermae sp. nov. from Cyanoderma ruficeps Blyth (Timaliidae); P. periparus sp. nov. from Periparus ater (Linnaeus) (Paridae); P. aegithalos sp. nov. from Aegithalos iouschistos bonvaloti (Oustalet) (Aegithalidae).

Effects of thermal stress on lipid peroxidation and antioxidant enzyme activities of the predatory mite, Neoseiulus cucumeris (Acari: Phytoseiidae).

Changes in temperature are known to cause a variety of physiological stress responses in insects and mites. Thermal stress responses are usually associated with the increased generation of reactive oxygen species (ROS), resulting in oxidative damage. In this study, we examined the time-related effect (durations for 1, 2, 3, and 5 h) of thermal stress conditions-i.e., relatively low (0, 5, 10, and 15 °C) or high (35, 38, 41, and 44 °C) temperatures-on the activities of antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), peroxidase (POX), glutathione S-transferases (GSTs), and total antioxidant capacity (T-AOC) of the predatory mite Neoseiulus cucumeris. Also the lipid peroxidation (LPO) levels of the predatory mite were measured under thermal stress conditions. The results confirmed that thermal stress results in a condition of so-called oxidative stress and the four antioxidant enzymes play an important role in combating the accumulation of ROS in N. cucumeris. CAT and POX activity changed significantly when the mites were exposed to cold and heat shock, respectively. The elevated levels of SOD and GSTs activity, expressed in a time-dependent manner, may have an important role in the process of antioxidant response to thermal stress. However, the levels of LPO in N. cucumeris were high, serving as an important signal that these antioxidant enzyme-based defense mechanisms were not always adequate to counteract the surplus ROS. Thus, we hypothesize that thermal stress, especially extreme temperatures, may contribute much to the generation of ROS in N. cucumeris, and eventually to its death.

[Characterization of biochar by X-ray photoelectron spectroscopy and 13C nuclear magnetic resonance].

The wood (willow branch) and grass (rice straw) materials were pyrolyzed at different temperatures (300, 450 and 600 °C) to obtain the biochars used in the present study. The biochars were characterized using elementary analysis, X-ray photoelectron spectroscopy (XPS) and solid state 13C cross-polarization and magic angle spinning nuclear magnetic resonance spectroscopy (13C NMR) to illuminate the structure and composition of the biochars which were derived from the different thermal temperatures and biomass. The results showed that the H/C, O/C and (O+N)/C ratios of the biochars decreased with the increase in the pyrolysis temperatures. The surface polarity and ash content of the grass-derived biochars were higher than those of the wood-derived biochars. The minerals of the wood-derived biochars were mainly covered by the organic matter; in contrast, parts of the mineral surfaces of the grass-derived biochars were not covered by organic matter? The 13C NMR of the low temperature-derived biochars revealed a large contribution of aromatic carbon, aliphatic carbon, carboxyl and carbonyl carbon, while the high temperature-derived biochars contained a large amount of aromatic carbon. Moreover, the wood-derived biochars produced at low heat treatment temperatures contained more lignin residues than grass-derived ones, probably due to the existence of high lignin content in the feedstock soures of wood-derived biochars. The results of the study would be useful for environmental application of biochars.

Toxicity comparison and risk assessment of two chlorinated organophosphate flame retardants (TCEP and TCPP) on Polypedates megacephalus tadpoles.

Tris(2-chloroethyl) phosphate (TCEP) and tris(1­chloro-2-propyl) phosphate (TCPP) are widely used as chlorinated organophosphate flame retardants (OPFRs) due to their fire-resistance capabilities. However, their extensive use has led to their permeation and pollution in aquatic environments. Using amphibians, which are non-model organisms, to test the toxic effects of OPFRs is relatively uncommon. This study examined the acute and chronic toxicity differences between TCEP and TCPP on Polypedates megacephalus tadpoles and evaluated the potential ecological risks to tadpoles in different aquatic environments using the risk quotient (RQ). In acute toxicity assay, the tadpole survival rates decreased with increased exposure time and concentrations, with TCEP exhibiting higher LC50 values than TCPP, at 305.5 mg/L and 70 mg/L, respectively. In the chronic assay, prolonged exposure to 300 µg/L of both substances resulted in similar adverse effects on tadpole growth, metamorphosis, and hepatic antioxidant function. Based on RQ values, most aquatic environments did not pose an ecological risk to tadpoles. However, the analysis showed that wastewater presented higher risks than rivers and drinking water, and TCPP posed a higher potential risk than TCEP in all examined aquatic environments. These findings provide empirical evidence to comprehend the toxicological effects of OPFRs on aquatic organisms and to assess the safety of aquatic environments.

[Determination of fatty acid composition after saponification of common oil pharmaceutical excipients by supercritical fluid-evaporative light scattering method and its application in oil identification].

Oils and fats are commonly used in the pharmaceutical industry as solvents, emulsifiers, wetting agents, and dispersants, and are an important category of pharmaceutical excipients. Fatty acids with unique compositions are important components of oil pharmaceutical excipients. The Chinese Pharmacopoeia provides clear descriptions of the fatty acid types and limits suitable for individual oil pharmaceutical excipient. An unqualified fatty acid composition or content may indicate adulteration or deterioration. The fatty acid composition, as a key indicator for the identification and adulteration evaluation of oil pharmaceutical excipients, can directly affect the quality and safety of oil pharmaceutical excipients and preparations. Gas chromatography is the most widely used technique for fatty acid analysis, but it generally requires derivatization, which affects quantitative accuracy. Supercritical fluid chromatography (SFC), an environmentally friendly technique with excellent separation capability, offers an efficient method for detecting fatty acids without derivatization. Unlike other chromatographic methods, SFC does not use nonvolatile solvents (e. g., water) as the mobile phase, rendering it compatible with an evaporative light-scattering detector (ELSD) for enhanced detection sensitivity. However, the fatty acids in oil pharmaceutical excipients exist in the free and bound forms, and the low content of free fatty acids in these oil pharmaceutical excipients not only poses challenges for their detection but also complicates the determination of characteristic fatty acid compositions and contents. Moreover, the compositions and ratios of fatty acids are influenced by environmental factors, leading to interconversion between their two forms. In this context, saponification provides a simpler and faster alternative to derivatization. Saponification degrades oils and fats by utilizing the reaction between esters and an alkaline solution, ultimately releasing the corresponding fatty acids. Because this method is more cost effective than derivatization, it is a suitable pretreatment method for the detection of fatty acids in oil pharmaceutical excipients using the SFC-ELSD approach. In this study, we employed SFC-ELSD to simultaneously determine six fatty acids, namely, myristic acid, palmitic acid, stearic acid, arachidic acid, docosanoic acid, and lignoceric acid, in oil pharmaceutical excipients. Saponification of the oil pharmaceutical excipients using sodium hydroxide methanol solution effectively avoided the bias in the determination of fatty acid species and contents caused by the interconversion of fatty acids and esters. The separation of the six fatty acids was achieved within 12 min, with good linearity within their respective mass concentration ranges. The limits of detection and quantification were 5-10 mg/L and 10-25 mg/L, respectively, and the spiked recoveries were 80.93%-111.66%. The method proved to be sensitive, reproducible, and stable, adequately meeting requirements for the analysis of fatty acids in oil pharmaceutical excipients. Finally, the analytical method was successfully applied to the determination of six fatty acids in five types of oil pharmaceutical excipients, namely, corn oil, soybean oil, coconut oil, olive oil, and peanut oil. It can be combined with principal component analysis to accurately differentiate different types of oil pharmaceutical excipients, providing technical support for the rapid identification and quality control of oil pharmaceutical excipients. Thus, the proposed method may potentially be applied to the analysis of complex systems adulterated with oil pharmaceutical excipients.

Effect of Cymbopogon martini (Roxb.) Will.Watson essential oil on antioxidant activity, immune and intestinal barrier-related function, and gut microbiota in pigeons infected by Candida albicans.

Essential oils are potential alternatives to antibiotics for preventing Candida albicans (C. albicans) infection which is responsible for economic losses in the pigeon industry. Cymbopogon martini essential oil (EO) can inhibit pathogens, particularly fungal pathogens but its potential beneficial effects on C. albicans-infected pigeons remain unclear. Therefore, we investigated the impact of C. martini EO on antioxidant activity, immune response, intestinal barrier function, and intestinal microbiota in C. albicans-infected pigeons. The pigeons were divided into four groups as follows: (1) NC group: C. albicans uninfected/C. martini EO untreated group; (2) PC group: C. albicans infected/C. martini EO untreated group; (3) LPA group: C. albicans infected/1% C. martini EO treated group; and (4) HPA group: C. albicans infected/2% C. martini EO treated group. The pigeons were infected with C. albicans from day of age 35 to 41 and treated with C. martini EO from day of age 42 to 44, with samples collected on day of age 45 for analysis. The results demonstrated that C. martini EO prevented the reduction in the antioxidant enzymes SOD and GSH-Px causes by C. albicans challenge in pigeons. Furthermore, C. martini EO could decrease the relative expression of IL-1ß, TGF-ß, and IL-8 in the ileum, as well as IL-1ß and IL-8 in the crop, while increasing the relative expression of Claudin-1 in the ileum and the crop and Occludin in the ileum in infected pigeons. Although the gut microbiota composition was not significantly affected by C. martini EO, 2% C. martini EO increased the abundance of Alistipes and Pedobacter. In conclusion, the application of 2% C. martini EO not only enhanced the level of antioxidant activity and the expression of genes related to intestinal barrier function but also inhibited inflammatory genes in C. albicans-infected pigeons and increased the abundance of gut bacteria that are resistant to C. albicans.

Dbl family RhoGEFs in cancer: different roles and targeting strategies.

Small Ras homologous guanosine triphosphatase (Rho GTPase) family proteins are highly associated with tumorigenesis and development. As intrinsic exchange activity regulators of Rho GTPases, Rho guanine nucleotide exchange factors (RhoGEFs) have been demonstrated to be closely involved in tumor development and received increasing attention. They mainly contain two families: the diffuse B-cell lymphoma (Dbl) family and the dedicator of cytokinesis (Dock) family. More and more emphasis has been paid to the Dbl family members for their abnormally high expression in various cancers and their correlation to poor prognosis. In this review, the common and distinctive structures of Dbl family members are discussed, and their roles in cancer are summarized with a focus on Ect2, Tiam1/2, P-Rex1/2, Vav1/2/3, Trio, KALRN, and LARG. Significantly, the strategies targeting Dbl family RhoGEFs are highlighted as novel therapeutic opportunities for cancer.

Biological Activities of p-Hydroxycinnamic Acids in Maintaining Gut Barrier Integrity and Function.

It is well established that p-Hydroxycinnamic acids (HCAs), including ferulic, caffeic, sinapic, and p-coumaric acids, possess a characteristic phenylpropanoid C6-C3 backbone and account for about one-third of the phenolic compounds in our diet. HCAs are typically associated with various plant cell wall components, including mono-, di-, and polysaccharides, sterols, polyamines, glycoproteins, and lignins. Interestingly, enzymes produced by intestinal microbes liberate HCAs from these associations. HCAs are completely absorbed in their free form upon ingestion and undergo specific reactions upon absorption in the small intestine or liver. The gut epithelium, composed of intestinal epithelial cells (IECs), acts as a physical barrier against harmful bacteria and a site for regulated interactions between bacteria and the gut lumen. Thus, maintaining the integrity of the epithelial barrier is essential for establishing a physiochemical environment conducive to homeostasis. This review summarizes the protective effects of HCAs on the intestinal barrier, achieved through four mechanisms: preserving tight junction proteins (TJPs), modulating pro-inflammatory cytokines, exerting antioxidant activity, and regulating the intestinal microbiota.

Effects of application of phosphate and phosphate-solubilizing bacteria on bacterial diversity and phosphorus fractions in a Phaeozems.

The aim of this study is to improve the utilization of phosphorus (P) in soil, and to study the effects of phosphate-solubilizing bacteria (PSB) on P fractions and bacterial communities. In this experiment, we reduced the amount of P fertilizer by 30 % and 40 % respectively to studied the effects of combined application of bacterial fertilizers on soil microbial community and phosphate transformation process under different fertilization rates. The results showed that the application of PSB affected the transformation process of different P fractions. PSB had the most significant impact on organic phosphorus (p < 0.05). Correlation analysis showed that the abundance of bacteria was significantly correlated to the P fractions, indicating that the application of PSB had affected the bacterial community structure. In addition, Structural Equation Model (SEM) analysis showed that there was a causal relationship between the various visual variables. SEM confirmed the response relationship between bacterial communities and P components. Based on these results, we concluded that the application of PSB increased the sensitivity of P components, especially Olsen-P and MBP, to soil microorganisms. The application of PSB is an effective method to improve P utilization.