Search

【Objective】The large-scale cultivation of white sapote in China is in its initial stage, and the adaptability of white sapote in Guangdong is not clear yet. Clarifying the phenology of white sapote in Guangdong as well as its flowering and fruiting habits and summarizing cultivation techniques can provide guidance for the large-scale cultivation of white sapote.【Method】A white sapote cultivar 'W4' was used as the research material to observe its botanical characteristics, phenology, fruit growth law, fruit setting and fruit quality. The key points of its high-quality cultivation techniques were expounded from aspects of garden construction, fertilizer and water management, shaping and pruning, pest control and fruit harvesting.【Result】The flowering period of white sapote on was from late January to early February, and there were three growth peaks of shoot growth in April, June and September, respectively. The slow growth period was from November to next February. During fruit growth and development, there were three fruit-dropping peaks, which were in mid-March, mid-April and May to June before harvest. The average fruit weight is 148.93 g, and the shape index is 0.83. The fruit melts in the mouth like ice cream, the edible rate is 79.7%, the soluble solid content is 20.36%, and the solid acid ratio is 45.83. White sapote can withstand a low temperature of-2--4℃, which is higher than the average temperature of the coldest month(January) in Guangdong. Therefore, it can be cultivated in most areas of Guangdong.【Conclusion】This variety has good growth potential, strong adaptability, large single fruit quality, good flavor and excellent quality, and has high economic benefit in the market. It is a new fruit variety with planting potential. Attention should be paid to preventing anthracnose and sooty blotch in cultivation.White sapote is suitable for planting on the slope with loose soil and good drainage and irrigation in Guangdong. Dwarfing treatment should be done and tree shape be controlled for young trees.

【Objective】Blueberry (Vaccinium spp.) is a plant species with no root hairs, resulting in weak uptake capacity of roots. Southern China is an emerging production area of blueberry. Therefore, the study aimed to investigate whether the soil conditions in southern China are suitable for blueberry growth and development, and whether the plant nutrients are balanced.【Method】With four blueberry cultivars in Heyuan, Guangdong Province as tested plants, the nutrient balance and levels in plants were studied with the method of Diagnosis and Recommendation Integrated System (DRIS) on the basis of leaf and soil analysis. The mycorrhizal colonization rate was determined, and the soil chemical properties affecting plant nutrient status were analyzed.【Result】There were significant differences in plant nutrient levels between cultivars, and the nutrient level of 'Sharpblue' was the highest. The contents of nitrogen, phosphorus and potassium in leaves were 15.90, 0.76 and 6.58 g/kg, respectively, and the iron content in leaves was 63.73 mg/kg.The total nutrient requirement of plants ranked as P>N>K. The levels of P and N were at a low range while that of K was at a normal range. It was noteworthy that there was no significant correlation between soil nutrient level and leaf nutrient level. The mycorrhizal colonization rate in roots was low (15.0%-26.7%), which led to a weak uptake capacity of roots.【Conclusion】The nutrient levels of blueberry plants in southern China are unbalanced, which are related to the weak root absorption capacity and low mycorrhizal colonization level. It is recommended that the application of P and N fertilizers, especially in organic forms, be increased and the application of mycorrhizal fungi be inoculated to improved the nutrient uptake efficiency.

Fruit peel creasing is a serious pre-harvest physiological disorder in citrus, influencing fruit quality, storage, and yield. Four- and eight-year-old ‘Hongjiang’ oranges grafted onto Canton lemon rootstocks were treated with calcium and calcium inhibitors, respectively, to study the effects of different treatments on fruit creasing rate, mechanical properties of the peel, cell wall metabolism enzyme activities, and the expression of related genes. Foliar application of 0.5% calcium nitrate significantly reduced the fruit creasing rate, while treatment with EGTA and LaCl3, inhibitors of calcium uptake, increased the fruit creasing rate; But the effect of calcium nitrate treatment on changing the mechanical properties of pericarp and inhibiting the activity of hydrolase (PG, Cx and PE) was not very significant. Furthermore, it was observed that the expression levels of genes (PG, Cx, and PE) encoding cell wall-degrading enzymes were significantly lower in the normal fruit peel than in the creased fruit peel. Meanwhile, the expression levels of PG, Cx, and PE were higher in the peel of shaded fruit than in the peel of exposed fruit. During the high incidence period of fruit creasing, calcium nitrate treatment down-regulated the expression of PG, Cx, and PE, while EGTA treatment up-regulated the expression of these genes. In conclusion, foliar spraying of calcium nitrate at the fruit rapid enlargement stage can increase the Ca content in the peel of ‘Hongjiang’ orange and significantly suppress the expression of cell wall degrading enzymes genes (PG, PE and Cx) in ‘Hongjiang’ orange peel during the high occurrence period of fruit creasing, resulting in reducing the occurrence of fruit creasing and cracking.

Abstract Background Mandarin ‘Shatangju’ is susceptible to Huanglongbing (HLB) and the HLB-infected fruits are small, off-flavor, and stay-green at the maturity period. To understand the relationship between pericarp color and HLB pathogen and the effect mechanism of HLB on fruit pericarp coloration, quantitative analyses of HLB bacterial pathogens and carotenoids and also the integrative analysis of metabolome and transcriptome profiles were performed in the mandarin ‘Shatangju’ variety with four different color fruits, whole green fruits (WGF), top-yellow and base-green fruits (TYBGF), whole light-yellow fruits (WLYF), and whole dark-yellow fruits (WDYF) that were infected with HLB. Results the HLB bacterial population followed the order WGF > TYBGF > WLYF > WDYF. And there were significant differences between each group of samples. Regarding the accumulation of chlorophyll and carotenoid, the chlorophyll-a content in WGF was the highest and in WDYF was the lowest. The content of chlorophyll-b in WGF was significantly higher than that in other three pericarps. There were significant differences in the total content of carotenoid between each group. WGF and TYBGF pericarps were low in phytoene, γ-carotene, β-cryptoxanthin and apocarotenal, while other kinds of carotenoids were significantly higher than those in WDYF. And WLYF was only short of apocarotenal. We comprehensively compared the transcriptome and metabolite profiles of abnormal (WGF, TYBGF and WLYF) and normal (WDYF, control) pericarps. In total, 2,880, 2,782 and 1,053 differentially expressed genes (DEGs), including 121, 117 and 43 transcription factors were identified in the three comparisons, respectively. The qRT-PCR confirmed the expression levels of genes selected from transcriptome. Additionally, a total of 77 flavonoids and other phenylpropanoid-derived metabolites were identified in the three comparisons. Most (76.65 %) showed markedly lower abundances in the three comparisons. The phenylpropanoid biosynthesis pathway was the major enrichment pathway in the integrative analysis of metabolome and transcriptome profiles. Conclusions Synthesizing the above analytical results, this study indicated that different color pericarps were associated with the reduced levels of some carotenoids and phenylpropanoids derivatives products and the down-regulation of proteins in flavonoids, phenylpropanoids derivatives biosynthesis pathway and the photosynthesis-antenna proteins.

Gamma-aminobutyric acid (GABA) is a non-protein amino acid known for its role in the nervous system of animals. However, research has also revealed its presence and function in plants recently. In plants, GABA is a signal molecule involved in multiple physiological processes, including stress response, growth, and development. This review aims to present a thorough summary of the current knowledge regarding the role of GABA in plants. We begin by discussing the biosynthesis and transport of GABA in plants, followed by a detailed examination of its signaling mechanisms. Additionally, we explore GABA's potential roles in various plant physiological processes, such as abiotic stress response, and its potential application in horticultural plants. Finally, we highlight current challenges and future directions for research in this area. Overall, this review offers a comprehensive understanding of the significance of GABA in plants and its potential implications for plant physiology and crop improvement.

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation and damage of colonocytes with etiology of genetic, epigenetic and environmental factors. MicroRNA-223 (miR-223) has been found to be increased in both IBD patients and animal colitis models. However, contentious opinions relevant to the roles of miR-223 in IBD have been reported. Notwithstading that most studies have described that miR-223 has anti-inflammatory effects, several reports have progressed a pro-inflammatory view. In this review, we summarise both the anti-inflammatory and pro-inflammatory effects of miR-223 on key molecules in inflammatory responses in both animal models and in patients diagnosed with IBD and objectively discuss the possible basis for the discrepancies.

Grafting has been utilized to develop horticultural crops to increase plant vigor, yield potential, and tolerance to various environmental stresses. Grafting employs selected rootstocks of the same species or near relatives. Moreover, dwarfing is a desirable feature for intensive cultivation and efficient orchard management. However, information on the regulatory mechanisms of rootstock-induced vigor control remains unclear. Numerous studies comprehend the physiological and molecular mechanism of rootstock control scion vigor, which has significantly improved our understanding regarding vigor control processes in apple, litchi, pear, citrus, etc. This review summarizes the current knowledge on the impact of rootstocks on scion vigor and hormonal mechanisms involved in dwarfing, such as auxin (IAA), cytokinins (CK), abscisic acid (ABA), gibberellic acids (GAs), and brassinosteroids (BR). This study will provide fascinating information for future studies on rootstock-induced dwarfing effects and accelerate the breeding of dwarfing rootstocks.

Most COVID-19 cases are mild or asymptomatic and recover well, suggesting that effective immune responses ensue, which successfully eliminate SARS-CoV-2 viruses. However, a small proportion of patients develop severe COVID-19 with pathological immune responses. This indicates that a strong immune system balanced with anti-inflammatory mechanisms is critical for the recovery from SARS-CoV-2 infections. Many vaccines against SARS-CoV-2 have now been developed for eliciting effective immune responses to protect from SARS-CoV-2 infections or reduce the severity of the disease if infected. Although uncommon, serious morbidity and mortality have resulted from both COVID-19 vaccine adverse reactions and lack of efficacy, and further improvement of efficacy and prevention of adverse effects are urgently warranted. Many factors could affect efficacy of these vaccines to achieve optimal immune responses. Dysregulation of the gut microbiota (gut dysbiosis) could be an important risk factor as the gut microbiota is associated with the development and maintenance of an effective immune system response. In this narrative review, we discuss the immune responses to SARS-CoV-2, how COVID-19 vaccines elicit protective immune responses, gut dysbiosis involvement in inefficacy and adverse effects of COVID-19 vaccines and the modulation of the gut microbiota by functional foods to improve COVID-19 vaccine immunisations.

Dwarfing is an important agricultural trait for intensive cultivation and effective orchard management in modern fruit orchards. Commercial citrus production relies on grafting with rootstocks that reduce tree vigor to control plant height. Citrus growers all over the world have been attracted to dwarfing trees because of their potential for higher planting density, increased productivity, easy harvest, pruning, and efficient spraying. Dwarfing rootstocks can be used to achieve high density. As a result, the use and development of dwarfing rootstocks are important. Breeding programs in several countries have led to the production of citrus dwarf rootstocks. For example, the dwarfing rootstocks ‘Flying Dragon’, ‘FA 517’, ‘HTR-051’, ‘US-897’, and ‘Red tangerine’ cultivated in various regions allow the design of dense orchards. Additionally, dwarf or short-stature trees were obtained using interstocks, citrus dwarfing viroid (CDVd) and various chemical applications. This review summarizes what is known about dwarf citrus rootstocks and the mechanisms underlying rootstock–scion interactions. Despite advances in recent decades, many questions regarding rootstock-induced scion development remain unanswered. Citrus rootstocks with dwarfing potential have been investigated regarding physiological aspects, hormonal communication, mineral uptake capacity, and horticultural performance. This study lays the foundation for future research into the genetic and molecular mechanisms underlying citrus dwarfing.

The main entry point of SARS-CoV-2 is the respiratory tract and as such immune defence in this site determines if the virus will spill-over to the systemic circulation and circulate and infect other major organs. The first line of mucosal immune defence is composed of mucins, an epithelial barrier, and immune cells in the nasal cavity. The lung immune defence is carried out by numerous alveoli. The lung microbiota is a key factor in determining the efficacy of lung mucosal immunity protection. The intestinal microbiota has been demonstrated to affect the severity of COVID-19. Gut dysbiosis is involved in hyperinflammation and multiple organ failure through communications with multiple organs. The gut lung axis could be the earliest axis affected in COVID-19. Through the gut-lung axis, gut dysbiosis can affect the pathogenesis of the lung in COVID-19. In this review, we summarise the effects that gut dysbiosis can progress on the lung, and the lung microbiota. The possible mechanisms and approaches for modulation are discussed.

Dwarfing rootstocks are a valuable genetic resource for managing high-density plantations. The selection of the appropriate scion/rootstock combination is key to improving crop performance and sustainable production in a particular environment and specific training systems. ‘Shatangju’ mandarin scion cultivar grafted onto ‘Flying Dragon’ rootstock tends to be dwarfing and develops short stature plants. To obtain insight into potential mechanisms underlying rootstock-induced dwarfing effects, we conducted a rootstock trial to examine the influence of 11 different rootstocks based on their growth vigor, antioxidants, and hormonal levels of the scion cultivar. The phenotypic observations revealed that size reduction in the ‘Flying Dragon’ rootstock is due to lower node number, shorter internodal length, and a reduced trunk diameter of the scion compared with more vigorous rootstocks. Antioxidant analysis showed that ‘Shatangju’ mandarin grafted onto ’Flying Dragon’ and ‘Trifoliate Orange’ rootstock had significantly lower peroxidase (POD) activity than other tested rootstocks. The hormonal analysis indicated that there were markedly lower amounts of abscisic acid (ABA) in ‘Shatangju’ mandarin grafted with ‘Flying Dragon’ rootstock. In addition, trees grafted with ‘Sour Pummelo’ and ‘Flying Dragon’ depicted minimum amounts of gibberellins (GA24). Moreover, several metabolites associated with organic acids, flavonoids, amino acids, and alkaloids responded differently in plants grafted with ‘Flying Dragon’ (dwarfing) and ‘Shatang Mandarin’ (vigorous) rootstocks. This study concluded that ‘Flying Dragon’ rootstock with a strong dwarfing effect has been proposed to improve high-density cultivation methods. These findings will provide useful insights for future research associated with rootstock-mediated dwarfing mechanisms of citrus rootstocks.

Citrus fruit creasing or cracking is a complex pre-harvest physiological disorder that causes significant economic losses. Recent studies have indicated that citrus fruit creasing or cracking is caused not only by genetic factors but also by environmental factors. By reviewing the relationship between citrus fruit creasing or cracking and peel mechanical properties, the cellular wall ultrastructure, cellular wall metabolism and modification, this paper summarized the mechanism of citrus creasing or cracking and further explained the effects of genetic factors and environmental factors (light, temperature, humidity, mineral nutrition and plant growth regulators) on citrus fruit creasing or cracking rate. Further studies were proposed to provide a sound theoretical basis on citrus fruit creasing or cracking.

Citrus is a globally consumed fruit with great popularity. Mandarin (Citrus reticulata cv. ‘Shatangju’) is a local variety, and its planting area and yield are the greatest regarding fruit tree planting in Guangdong Province, China. However, its resistance to Huanglongbing (HLB) is weak. After infection by HLB, the fruits cannot develop normally. In this study, four kinds of fruits were classified as HBG, XQG, ZQG, and DHG, according to the color of their peels. The metabolomes of the three abnormally colored groups (HBG, XQG, and ZQG) and the normally colored group (DHG) were compared using a UPLC-QQQ-MS-based metabolomics approach. In total, 913 metabolites were identified and classified into 23 different categories, including phenylpropanoids and flavonoids; among them, 215 (HBG, 177; XQG, 124; and ZQG, 62) metabolites showed differential accumulation in the three comparison groups (HBG/XQG/ZQG versus DHG). A total of 2 unique metabolites, O-caffeoyl maltotriose and myricetin were detected only in DHG samples. When comparing HBG with DHG, there were 109 decreased and 68 increased metabolites; comparing XQG with DHG, there were 88 decreased and 36 increased metabolites; comparing ZQG with DHG, 41 metabolites were decreased, and 21 metabolites were increased. Metabolic pathway enrichment analysis of these differential metabolites showed significant enrichment of the “phenylpropanoid biosynthesis” pathway in all comparison groups. The hierarchical cluster analysis of the differential metabolites of the four groups showed a clear grouping patterns. The relative contents of three phenylpropanoids, four flavonoids, two alkaloids, one anthocyanin, and two other metabolites were significantly different between each comparison group. This study might provide fundamental insight for the isolation and identification of functional compounds from the peels of citrus fruit infected with HLB and for in-depth research on the effect of HLB on the formation of fruits pigment and the development of HLB-resistant citrus varieties.

Antipsychotic drugs (APDs) are widely prescribed to control various mental disorders. As mental disorders are chronic diseases, these drugs are often used over a life-time. However, APDs can cause serious glucometabolic side-effects including type 2 diabetes and hyperglycaemic emergency, leading to medication non-compliance. At present, there is no effective approach to overcome these side-effects. Understanding the mechanisms for APD-induced diabetes should be helpful in prevention and treatment of these side-effects of APDs and thus improve the clinical outcomes of APDs. In this review, the potential mechanisms for APD-induced diabetes are summarized so that novel approaches can be considered to relieve APD-induced diabetes. APD-induced diabetes could be mediated by multiple mechanisms: (1) APDs can inhibit the insulin signaling pathway in the target cells such as muscle cells, hepatocytes and adipocytes to cause insulin resistance; (2) APD-induced obesity can result in high levels of free fatty acids (FFA) and inflammation, which can also cause insulin resistance. (3) APDs can cause direct damage to β-cells, leading to dysfunction and apoptosis of β-cells. A recent theory considers that both β-cell damage and insulin resistance are necessary factors for the development of diabetes. In high-fat diet-induced diabetes, the compensatory ability of β-cells is gradually damaged, while APDs cause direct β-cell damage, accounting for the severe form of APD-induced diabetes. Based on these mechanisms, effective prevention of APD-induced diabetes may need an integrated approach to combat various effects of APDs on multiple pathways.

Arbuscular mycorrhizal fungi (AMF) establish symbiosis with most terrestrial plants, and greatly regulate lateral root (LR) formation. Phosphorus (P), sugar, and plant hormones are proposed being involved in this regulation, however, no global evidence regarding these factors is available so far, especially in woody plants. In this study, we inoculated trifoliate orange seedlings (Poncirus trifoliata L. Raf) with an AMF isolate, Rhizophagus irregularis BGC JX04B. After 4 months of growth, LR formation was characterized, and sugar contents in roots were determined. RNA-Seq analysis was performed to obtain the transcriptomes of LR root tips from non-mycorrhizal and mycorrhizal seedlings. Quantitative real time PCR (qRT-PCR) of selected genes was also conducted for validation. The results showed that AMF significantly increased LR number, as well as plant biomass and shoot P concentration. The contents of glucose and fructose in primary root, and sucrose content in LR were also increased. A total of 909 differentially expressed genes (DEGs) were identified in response to AMF inoculation, and qRT-PCR validated the transcriptomic data. The numbers of DEGs related to P, sugar, and plant hormones were 31, 32, and 25, respectively. For P metabolism, the most up-regulated DEGs mainly encoded phosphate transporter, and the most down-regulated DEGs encoded acid phosphatase. For sugar metabolism, the most up-regulated DEGs encoded polygalacturonase and chitinase. For plant hormones, the most up-regulated DEGs were related to auxin signaling, and the most down-regulated DEGs were related to ethylene signaling. PLS-SEM analysis indicates that P metabolism was the most important pathway by which AMF regulates LR formation in this study. These data reveal the changes of genome-wide gene expression in responses to AMF inoculation in trifoliate orange and provide a solid basis for the future identification and characterization of key genes involved in LR formation induced by AMF.

Background: The objective of this study was to report a case series on the efficacy and safety of capecitabine 7/7 schedule combined with erlotinib (CAP-ERL) in patients with advanced pancreatic cancer (APC) who have failed prior therapies. Methods: We retrospectively evaluated 13 patients with locally advanced or metastatic pancreatic cancer previously treated with gemcitabine or oxaliplatin–irinotecan-based first-line regimens. Treatment consisted of capecitabine (Xeloda) at a flat dose of 1000 mg orally twice daily on days 1–7 out of 14 days (7/7 schedule) and erlotinib (Tarceva) 100 mg orally once daily until unacceptable toxicity or disease progression. Tumor assessments were repeated every two cycles (8 weeks) and serum tumor markers were measured every 4 weeks. Results: All patients (median age: 63 years; 7 female/3 male) had various previous lines of treatments of chemotherapies. Median number of cycles with CAP-ERL was 4 (range 2–12). The overall response rate was 20%. CA19-9 was reduced more than 25% in 40% patients. The median overall survival and progression-free survival from the start of CAP-ERL were 4.5 months (range 3–7.5) and 2 months (range 1.5–4), respectively. The most common grade 3 toxicities included hand–foot syndrome, nausea, vomiting, diarrhea, rash, and fatigue. Conclusions: Our result suggests that the combination of a fixed low dose of CAP-ERL 7/7 schedule was tolerated with manageable toxicity and showed encouraging activity as salvage treatment in patients with refractory APC with ECOG performance status 0–2. Further prospective studies are warranted to evaluate this combination.

Mitochondrial functions are crucial for pancreatic β-cell survival and glucose-induced insulin secretion. Hexarelin (Hex) is a synthetic small peptide ghrelin analogue, which has been shown to protect cardiomyocytes from the ischemia-reperfusion process. In this study, we used in vitro and in vivo models of streptozotocin (STZ)-induced β-cell damage to study the protective effect of Hex and the associated mechanisms. We found that STZ produced a cytotoxic effect in a dose- and time-dependent manner in MIN6 cells (a mouse β-cell line). Hex (1.0 μM) decreased the STZ-induced damage in β-cells. Rhodamine 123 assay and superoxide DHE production assay revealed that Hex ameliorated STZ-induced mitochondrial damage and excessive superoxide activity in β-cells. In addition, Hex significantly reduced STZ-induced expression of cleaved Caspases-3, Caspases-9 and the ratio of pro-apoptotic protein Bax to anti-apoptotic protein Bcl-2 in MIN6 cells. We further examined the in vivo effect of Hex in a rat model of type 1 diabetes induced by STZ injection. Hex ameliorated STZ-induced decrease in plasma insulin and protected the structure of islets from STZ-induced disruption. Hex also ameliorated STZ-induced expression of cleaved Caspase-9 and the Bax in β-cells. In conclusion, our data indicate that Hex is able to protects β-cell mass from STZ-caused cytotoxic effects involving mitochondrial pathways in vitro and in vivo. Hex may serve as a potential protective agent for the management of diabetes.

Chest X-ray and CT examinations often find pulmonary nodules that could be malignant or benign. A case is presented and discussed here in order to improve diagnosis and management of pulmonary nodules. A 62-year-old lady was found to have multiple pulmonary nodules by X-ray when she complained of a cough and fever. This was confirmed by a CT scan. Fine needle aspiration (FNA) of one of the lung lesions reported scant atypical epithelial cells that stained positive for TTF-1 and cytokeratin 7, but negative for cytokeratin 20. Thus, it was suspicious for large cell carcinoma. A videothoracoscopic lung biopsy and histopathology were applied and showed a necrotic nodule with surrounding chronic inflammation and macrophage response, with no evidence of malignant cells. Atypical reactive pneumocytes at the periphery of the lesion (an old infarct) were probably equivalent to the atypical cells seen on cytology. This result changed the diagnosis of our patient from a malignant condition to a benign process. Thus, CT and FNA may give a false positive. A second pathological opinion is very useful for the right diagnosis and management, as shown in our case.

Obesity and overweight have become major medical and social problems. Both are increasing worldwide; two-thirds of the population in developed countries is obese or overweight. Obesity has been associated with many comorbidities, including diabetes and heart disease. Studies have also found that obesity is one of the risk factors involved in increased cancer incidence. Many obesity-related factors are responsible, including increased blood levels of insulin/IGF, IL-6, TNF-alpha, and leptin, and decreased blood levels of adiponectin. Recently, it has been shown that IL-17 levels increase in obese patients. IL-17 is well known to increase carcinogenesis; thus, increased IL-17 levels in obesity may contribute to increased cancer incidence in obesity. IL-17 could activate Src/PI3K, MAPK, Stat3, and PKC, resulting in carcinogenesis. It may also change the microenvironment of tumors. Thus, inhibition of IL-17 may have preventive and therapeutic implications in obese patients.

Jiezhong Chen1,3, Kenneth Raymond21John Curtin School of Medical Research, Australian National University, Acton, ACT, Australia; 2School of Pharmacy and Applied Science, Faculty of Science, Technology and Engineering, LaTrobe University, Bendigo, Vic, Australia; 3Adjunct Senior Research Fellow, University of Canberra, ACT, AustraliaAbstract: Diabetes mellitus is characterized by high blood glucose level with typical manifestations of thirst, polyuria, polydipsia, and weight loss. It is caused by defects in insulin-mediated signal pathways, resulting in decreased glucose transportation from blood into muscle and fat cells. The major risk is vascular injury leading to heart disease, which is accelerated by increased lipid levels and hypertension. Management of diabetes includes: control of blood glucose level and lipids; and reduction of hypertension. Dietary intake of beta-glucans has been shown to reduce all these risk factors to benefit the treatment of diabetes and associated complications. In addition, beta-glucans also promote wound healing and alleviate ischemic heart injury. However, the mechanisms behind the effect of beta-glucans on diabetes and associated complications need to be further studied using pure beta-glucan.Keywords: diabetes mellitus, hyperglycemia, prevalence, pathogenesis

Aripiprazole is a wide-used antipsychotic drug with therapeutic effects on both positive and negative symptoms of schizophrenia, and reduced side-effects. Although aripiprazole was developed as a dopamine D2 receptor (D2R) partial agonist, all other D2R partial agonists that aimed to mimic aripiprazole failed to exert therapeutic effects in clinic. The present in vivo study aimed to investigate the effects of aripiprazole on the D2R downstream cAMP-PKA and Akt-GSK3β signalling pathways in comparison with a D2R antagonist--haloperidol and a D2R partial agonist--bifeprunox. Rats were injected once with aripiprazole (0.75 mg/kg, i.p.), bifeprunox (0.8 mg/kg, i.p.), haloperidol (0.1 mg/kg, i.p.) or vehicle. Five brain regions--the prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CPu), ventral tegmental area (VTA) and substantia nigra (SN) were collected. The protein levels of PKA, Akt and GSK3β were measured by Western Blotting; the cAMP levels were examined by ELISA tests. The results showed that aripiprazole presented similar acute effects on PKA expression to haloperidol, but not bifeprunox, in the CPU and VTA. Additionally, aripiprazole was able to increase the phosphorylation of GSK3β in the PFC, NAc, CPu and SN, respectively, which cannot be achieved by bifeprunox and haloperidol. These results suggested that acute treatment of aripiprazole had differential effects on the cAMP-PKA and Akt-GSK3β signalling pathways from haloperidol and bifeprunox in these brain areas. This study further indicated that, by comparison with bifeprunox, the unique pharmacological profile of aripiprazole may be attributed to the relatively lower intrinsic activity at D2R.

Tumour necrosis factor-α, interferon-γ and interleukin-4 are critical cytokines in regulating the immune responses against infections and tumours. In this study, we investigated the effects of three cytokines on CD40 expression in Myb-transformed hematological cells and their regulatory roles in promoting these cells into dendritic cells. We observed that both interleukin-4 and interferon-γ increased CD40 expression in these hematological cells in a dose-dependent manner, although the concentration required for interleukin-4 was significantly higher than that for interferon-γ. We found that tumour necrosis factor-α promoted CD40 expression induced by interferon-γ, but not by interleukin-4. Our data showed that tumour necrosis factor-α plus interferon-γ-treated Myb-transformed hematological cells had the greatest ability to take up and process the model antigen DQ-Ovalbumin. Tumour necrosis factor-α also increased the ability of interferon-γ to produce the mixed lymphocyte reaction to allogenic T cells. Furthermore, only cotreatment with tumour necrosis factor-α and interferon-γ induced Myb-transformed hematological cells to express interleukin-6. These results suggest that tumour necrosis factor-α plays a key regulatory role in the development of dendritic cells from hematological progenitor cells induced by interferon-γ.

Non-alcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH), which may then progress to the development of cirrhosis and hepatocarcinoma. NASH is characterized by both steatosis and inflammation. Control of inflammation in NASH is a key step for the prevention of disease progression to severe sequalae. Intestinal dysbiosis has been recognized to be an important causal factor in the pathogenesis of NASH, involving both the accumulation of lipids and aggravation of inflammation. The effects of gut dysbiosis are mediated by adverse shifts of various intestinal commensal bacterial genera and their associated metabolites such as butyrate, tryptophan, and bile acids. In this review, we focus on the roles of tryptophan and its metabolites in NASH in association with intestinal dysbiosis and discuss possible therapeutic implications. [ABSTRACT FROM AUTHOR]

The hominoid vermiform appendix has been characterized as a diverticulum of the caecum and describes an entity at the juxtaposition of the colon in the confluence of tanias. The independent development of the lymphoid follicle centres of the appendix is progressed at birth in the presence of the intestinal commensal microbiome, an obligatory prompt for the diversification of intestinal and extra-intestinal mucosal immunological tissue. In the vermiform appendix, this activity is centred on further developing the inventory of primary antibodies and the maturation of T- and B-lymphocyte cells in the follicles within the lymphoid tissue. Furthermore, the columnar epithelia, enterocytes and goblet cells comprise the complement of cells that occupy the lamina propria and muscularis mucosae of the vermiform appendix's mucosa, while macrophages and an abundance of immunoglobulin A and immunoglobulin G generating plasma cells seed the lamina propria. Intraepithelial immune cells consisting predominantly of specific CD8+ T regulatory lymphocytes occupy sites in the appendix analogous to those present in the intestinal epithelia of the caecal colon. The complement of bacterial genera concealed in the vermiform appendix is posited extant as a biofilm inoculum of the intestinal commensal microbiome. This facilitates re-inoculation of the proximal colon and to a lesser degree the terminal ilium post an intestinal perturbation such as occurs with daily lifestyle stressors, dietary choices and the short-term administration of antibiotics rather than an infectious fulminant colitis. A plausible appreciation results of the importance of multiple immunological aspects of a healthy vermiform appendix and the provision of a commensal biofilm to the gut that repairs a dysbiotic microbiome contributing to balancing intestinal pro- and anti-inflammatory activity for maintaining homeostasis in the gut. Since the composition of the gut microbiome can vary over the short-term and long-term, it is plausible that the appendix inoculum may be instrumental in maintaining the intestinal microbiome. [ABSTRACT FROM AUTHOR]

Over 99% of cervical cancers are associated with infection of high-risk type human papillomaviruses (HPV). These viruses infect epithelial cells lining the cervix and express the early viral genes E6 and E7, which are oncogenes and are primarily responsible for the transformation of the epithelial cells. The continuous expression of those genes is essential for maintenance of the cancer cell phenotype and viability. These viral genes can be silenced using oligonucleotide-based techniques, for example RNAi, antisense RNA and ribozymes. In spite of promising results in vitro and in vivo, in mice, these methods have thus far proved unsuccessful in humans, owing to the lack of an effective delivery system amongst other limitations. In this review we will discuss potential gene-silencing strategies in cervical cancer that would target both viral genes such as E6 and E7, and cellular genes that become deregulated such as E2F, p53, Akt, mTor, NF-κB or Bcl-2. By investigating these approaches we may generate an effective treatment for HPV-induced cervical cancer using gene silencing. [ABSTRACT FROM AUTHOR]

Rifampicin, an important drug in the treatment of tuberculosis, is used extensively despite its broad effects on drug-drug interactions, creating serious problems. The clinical importance of such interactions includes autoinduction leading to suboptimal or failed treatment. The concomitantly administered effects of rifampicin on other drugs can result in their altered metabolism or transportation that are metabolised by cytochromes P450 or transported by p-glycoprotein in the gastrointestinal tract and liver. This review paper summarises recent findings with emphases on the molecular mechanisms used to explain these broad drug-drug interactions. In general, rifampicin can act on a pattern: rifampicin activates the nuclear pregnane X receptor that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. This pattern of action may explain many of the rifampicin inducing drug-drug interactions. However, effects through other mechanisms have also been reported and these make any explanation of such drug-drug interactions more complex. [ABSTRACT FROM AUTHOR]

Influenza is an infectious disease and can lead to life-threatening complications like pneumonia. The disease is caused by three types of RNA viruses called influenza types A, B and C, each consisting of eight negative single-stranded RNA-segments encoding 11 proteins. Current annual vaccines contain two type A strains and one type B strain and are capable of inducing strong antibody responses to both the surface glycoprotein hemagglutinin and the neuraminidase. While these vaccines are protective against vaccine viruses they are not effective against newly emerging viruses that contain antigenic variations known as antigenic drift and shift. In nature, environmental selection pressure generally plays a key role in selecting antigenic changes in the antigen determining spots of hemagglutinin, resulting in changes in the antigenicity of the virus. Recently, a new technology has been developed where influenza-specific IgG+ antibody-secreting plasma cells can be isolated and cloned directly from vaccinated humans and high affinity monoclonal antibodies can be produced within several weeks after vaccination. The new technology holds great promise for the development of effective passive antibody therapy to limit the spread of influenza viruses in a timely manner. [ABSTRACT FROM AUTHOR]