Role of B Lymphocytes in the Pathogenesis of NAFLD: A 2022 Update.

Non-alcoholic fatty liver disease and its related complications are becoming one of the most important health problems globally. The liver functions as both a metabolic and an immune organ. The crosstalk between hepatocytes and intrahepatic immune cells plays a key role in coordinating a dual function of the liver in terms of the protection of the host from antigenic overload as a result of receiving nutrients and gut microbiota antigenic stimulation via facilitating immunologic tolerance. B cells are the most abundant lymphocytes in the liver. The crucial role of intrahepatic B cells in energy metabolism under different immune conditions is now emerging in the literature. The accumulating evidence has demonstrated that the antibodies and cytokines produced by B cells in the microenvironment play key and distinct roles in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Herein, we have aimed to consolidate and update the current knowledge about the pathophysiological roles of B cells as well as the underlying mechanisms in energy metabolism. Understanding how B cells can exacerbate and suppress liver damage by exploiting the antibodies and cytokines they produce will be of great importance for designing B-cell targeting therapies to treat various liver diseases.

Combined Catalpol and Tetramethylpyrazine Promote Axonal Plasticity in Alzheimer's Disease by Inducing Astrocytes to Secrete Exosomes Carrying CDK5 mRNA and Regulating STAT3 Phosphorylation.

Alzheimer's disease (AD) is a common progressive degenerative disease of the central nervous system in aging populations. This study aimed to investigate the effects of combined catalpol and tetramethylpyrazine (CT) in promoting axonal plasticity in AD and the potential underlying mechanism. Astrocytes were treated with different concentrations of compatible CT. Exosomes were collected and subjected to sequencing analysis, which was followed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes. Amyloid precursor protein/presenilin 1 (APP/PS1) double-transfected male mice were used as the in vivo AD models. Astrocyte-derived exosomes that were transfected with cyclin-dependent kinase 5 (CDK5) or CT treatment were injected into the tail vein of mice. The levels of CDK5, synaptic plasticity marker protein neurofilament 200 (NF200), and growth-associated protein 43 (GAP-43) in the hippocampus of mice were compared in each group. Immunofluorescence staining was used to detect the localization of STAT3 and to visualize synaptic morphology via ß-tubulin-III (TUBB3). Astrocyte-derived exosomes transfected with siCDK5 or treated with CT were co-cultured with HT-22 cells, which were untransfected or silenced for signal transducer and activator of transcription 3 (STAT3). Amyloid ß-protein (Aß)1-42 was induced in the in vitro AD models. The viability, apoptosis, and expression levels of NF200 and GAP-43 proteins in the hippocampal neurons of each group were compared. In total, 166 differentially expressed genes in CT-induced astrocyte-derived exosomes were included in the KEGG analysis, and they were found to be enriched in 12 pathways, mainly in axon guidance. CT treatment significantly increased the level of CDK5 mRNA in astrocyte-derived exosomes-these exosomes restored CDK5 mRNA and protein levels in the hippocampus of the in vivo AD model mice and the in vitro AD model; promoted p-STAT3 (Ser727), NF200 and GAP-43 proteins; and promoted the regeneration and extension of neuronal synapses. Silencing of CDK5 blocked both neuronal protection as well as induction of axonal plasticity in AD by CT-treated exosomes in vitro and in vivo. Moreover, silencing of STAT3 blocked both neuronal protection as well as induction of axonal plasticity in AD caused by CDK5 overexpression or CT-treated astrocyte-induced exosomes. CT promotes axonal plasticity in AD by inducing astrocytes to secrete exosomes carrying CDK5 mRNA and regulating STAT3 (Ser727) phosphorylation.

Tetramethylpyrazine ameliorates systemic streptozotocin-induced Alzheimer-like pathology.

Diabetes mellitus (DM) and its complications are the main threats to the global disease burden. DM-related cognitive dysfunction is a progressive neurodegenerative disease, similar to Alzheimer's disease (AD). The underlying pathophysiology remains unclear, and an effective treatment is unavailable. Tetramethylpyrazine (TMP) is a bioactive ingredient extracted from the plant Ligusticum wallichii, which has anti-diabetic and neuroprotective properties. In this study, streptozotocin (STZ) injection was used to establish a mouse STZ-AD model, and TMP was administered through the lateral ventricle (ICV) to evaluate the effects of TMP on cognitive ability and neurochemical changes and to explore the underlying cellular and molecular mechanisms. Using MWM and Y-maze behavioral paradigms, we observed that TMP protected against STZ-induced learning and memory impairment. STZ promoted the deposition of amyloid plaques, activation of glial cells, loss of neurons and synapses, and reduction of synaptic plasticity. In contrast, TMP restored these aberrations and improved cognitive deficits in STZ-induced diabetic animals. Moreover, TMP attenuated hippocampal mitochondrial dysfunction and oxidative stress through modulation of the SIRT1/Nrf2/ HO-1 pathway. This evidence shows that TMP exerts its therapeutic effects through multiple pathways. Our study provides new insights into the neuroprotective effects of TMP for the treatment of diabetes-related cognitive failure.

Effects of TCM on polycystic ovary syndrome and its cellular endocrine mechanism.

Polycystic ovary syndrome (PCOS) is a reproductive endocrine disease characterized by menstrual disorders, infertility, and obesity, often accompanied by insulin resistance and metabolic disorders. The pathogenesis of PCOS is relatively complex and has a certain relationship with endocrine disorders. The increase of androgen and luteinizing hormone (LH) is the main cause of a series of symptoms. Traditional Chinese medicine (TCM) has obvious advantages and significant curative effects in the treatment of this disease. It can effectively reduce the insulin level of PCOS patients, regulate lipid metabolism, and increase ovulation rate and pregnancy rate and has fewer side effects. This article reviews the efficacy and safety of Chinese herbs and other TCM (such as acupuncture) in the treatment of PCOS and its complications in recent years, as well as the effect and mechanism on cellular endocrine, in order to provide a new clinical idea for the treatment of PCOS.

Amelioration of non-alcoholic fatty liver disease by targeting adhesion G protein-coupled receptor F1 (Adgrf1).

Background: Recent research has shown that the adhesion G protein-coupled receptor F1 (Adgrf1; also known as GPR110; PGR19; KPG_012; hGPCR36) is an oncogene. The evidence is mainly based on high expression of Adgrf1 in numerous cancer types, and knockdown Adgrf1 can reduce the cell migration, invasion, and proliferation. Adgrf1 is, however, mostly expressed in the liver of healthy individuals. The function of Adgrf1 in liver has not been revealed. Interestingly, expression level of hepatic Adgrf1 is dramatically decreased in obese subjects. Here, the research examined whether Adgrf1 has a role in liver metabolism. Methods: We used recombinant adeno-associated virus-mediated gene delivery system, and antisense oligonucleotide was used to manipulate the hepatic Adgrf1 expression level in diet-induced obese mice to investigate the role of Adgrf1 in hepatic steatosis. The clinical relevance was examined using transcriptome profiling and archived biopsy specimens of liver tissues from non-alcoholic fatty liver disease (NAFLD) patients with different degree of fatty liver. Results: The expression of Adgrf1 in the liver was directly correlated to fat content in the livers of both obese mice and NAFLD patients. Stearoyl-coA desaturase 1 (Scd1), a crucial enzyme in hepatic de novo lipogenesis, was identified as a downstream target of Adgrf1 by RNA-sequencing analysis. Treatment with the liver-specific Scd1 inhibitor MK8245 and specific shRNAs against Scd1 in primary hepatocytes improved the hepatic steatosis of Adgrf1-overexpressing mice and lipid profile of hepatocytes, respectively. Conclusions: These results indicate Adgrf1 regulates hepatic lipid metabolism through controlling the expression of Scd1. Downregulation of Adgrf1 expression can potentially serve as a protective mechanism to stop the overaccumulation of fat in the liver in obese subjects. Overall, the above findings not only reveal a new mechanism regulating the progression of NAFLD, but also proposed a novel therapeutic approach to combat NAFLD by targeting Adgrf1. Funding: This work was supported by the National Natural Science Foundation of China (81870586), Area of Excellence (AoE/M-707/18), and General Research Fund (15101520) to CMW, and the National Natural Science Foundation of China (82270941, 81974117) to SJ.

Being overweight or obese increases the risk of developing numerous medical conditions including non-alcoholic fatty liver disease (NAFLD), where excess fat accumulates in the liver. NAFLD is a major global health issue affecting about 25% of the world's population and, if left untreated, can lead to liver inflammation as well as serious complications such as type 2 diabetes, heart disease, and liver cancer. Currently, there are no medications which specifically treat NFALD. Instead, only medications which help to manage the associated health complications are available. Therefore, a better understanding of NFALD is required to help to develop new strategies for diagnosing and treating the progression of this disease. A family of proteins known as GPCRs have crucial roles in regulating various bodily processes and are therefore commonly targeted for the treatment of disease. By identifying the GPCRs specifically involved in liver fat accumulation, new treatments for NFALD could be identified. Previous studies identified a GPCR known as Adgrf1 that is mainly found in liver cells, but its role remained unclear. To investigate the function of Adgrf1 in the liver, Wu et al. studied obese mice and human patients with NAFLD. The experiments showed that elevated levels of Adgrf1 in human and mouse livers led to increased fat accumulation. On the other hand, livers with lower levels of Adgrf1 exhibited reduced fat levels. A technique called RNA sequencing revealed that Adgrf1 induces expression of enzymes involved in fat synthesis, including a key regulator called Scd1. Treating mice with high levels of liver fat with molecules that inhibit Scd1 decreased the symptoms of Adgrf1-mediated fatty liver disease. These findings suggest therapies that decrease the levels of Adgrf1 may help to stop too much fat accumulating in the liver of human patients who are at risk of developing NAFLD. Further research is needed to confirm the effectiveness and safety of targeting Adgrf1 in humans and to develop suitable candidate drugs for the task.

Gastrodin and Vascular Dementia: Advances and Current Perspectives.

Gastrodia elata, a traditional Chinese medicine, has been widely used since ancient times to treat diseases such as dizziness, epilepsy, stroke, and memory loss. Gastrodin, one of the active components of Gastrodia elata, has been used in the treatment of migraine, epilepsy, Parkinson's disease, dementia, and depression in recent years. It can improve cognitive function and related neuropsychiatric symptoms through various effects and is considered as a promising treatment for dementia. Vascular dementia is a kind of severe cognitive impairment syndrome caused by vascular factors, and it is the dementia syndrome with the largest number of patients besides Alzheimer's disease. Although there is still a lack of evidence-based explorations, the paper reviewed the mechanism and methods of gastrodin in the treatment of vascular dementia, providing a reference for clinical therapy.

Multiple Roles of Paeoniflorin in Alzheimer's Disease.

Alzheimer's disease (AD) is a geriatric disease with the morbidity and mortality continuing to grow, partly due to the aging of the world population. As one of the most common types of primary neurodegenerative dementia, it is mainly due to environmental, epigenetic, immunological, and genetic factors. Paeoniflorin (PF), the main component of paeony extract, plays a more and more important role in the prevention and treatment of AD, including regulating protein, anti-inflammation, antioxidation, and antiapoptosis, protecting glial cells, regulating neurotransmitters and related enzymes and receptors, and inhibiting or activating related signal pathways. This article summarizes the latest researches on the multiple effects and the mechanisms of PF in the treatment to cure AD, providing new insights and research basis for further clinical application of traditional Chinese medicine (TCM) in the treatment of AD.

Effects of Catalpol on Alzheimer's Disease and Its Mechanisms.

Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by memory loss and cognitive dysfunction. With the increasing aging of the population, the incidence of AD and the number of patients are also increasing year by year, causing more and more heavy burdens to the family and society. Catalpol, an iridoid glycoside compound, is one of the main active components of Rehmannia glutinosa. At present, a large number of experimental studies in vivo and in vitro have confirmed that catalpol has antioxidant, anti-inflammatory, antiapoptotic, and other neuroprotective effects, and it plays a significant role in the prevention and treatment of AD, with very small side effects and high safety. Therefore, it may be an ideal drug for the treatment of AD. Based on this, the role and mechanism of catalpol in AD will be comprehensively reviewed in the following.

Roles of traditional chinese medicine regulating neuroendocrinology on AD treatment.

The incidence of sporadic Alzheimer's disease (AD) is increasing in recent years. Studies have shown that in addition to some genetic abnormalities, the majority of AD patients has a history of long-term exposure to risk factors. Neuroendocrine related risk factors have been proved to be strongly associated with AD. Long-term hormone disorder can have a direct detrimental effect on the brain by producing an AD-like pathology and result in cognitive decline by impairing neuronal metabolism, plasticity and survival. Traditional Chinese Medicine(TCM) may regulate the complex process of endocrine disorders, and improve metabolic abnormalities, as well as the resulting neuroinflammation and oxidative damage through a variety of pathways. TCM has unique therapeutic advantages in treating early intervention of AD-related neuroendocrine disorders and preventing cognitive decline. This paper reviewed the relationship between neuroendocrine and AD as well as the related TCM treatment and its mechanism. The advantages of TCM intervention on endocrine disorders and some pending problems was also discussed, and new insights for TCM treatment of dementia in the future was provided.

Research Progress of Targeting Neuro-Immune Inflammation in the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by extracellular senile plaques and the formation of intracellular neurofibrillary tangles. The accumulation of toxic beta-amyloid (Aß) induces the overproduction of reactive oxygen species (ROS), nitric oxide (NO) and pro-inflammatory cytokines. Accumulating studies suggest that neuroinflammatory mechanism plays an important role in the occurrence and development of AD. Microglia, astrocytes, macrophages, mast cells and T cells are involved in the pathogenesis of AD through neuroimmune mechanisms and inflammatory reactions. In recent years, many new drugs have been developed for the treatment of AD targeting neuroimmune and inflammatory mechanisms. Although some drugs failed in the Ⅲ phase of clinical trial, they made sense on subsequent research. This paper mainly discusses the positive effects on AD according to immunotherapy, anti-inflammatory treatment and regulation of immune inflammation by traditional Chinese medicine, in order to benefit for prevention or treatment of AD in the future.

Potential cellular endocrinology mechanisms underlying the effects of Chinese herbal medicine therapy on asthma.

Asthma is a complex syndrome with polygenetic tendency and multiple phenotypes, which has variable expiratory airflow limitation and respiratory symptoms that vary over time and in intensity. In recent years, continuous industrial development has seriously impacted the climate and air quality at a global scale. It has been verified that climate change can induce asthma in predisposed individuals and that atmospheric pollution can exacerbate asthma severity. At present, a subset of patients is resistant to the drug therapy for asthma. Hence, it is urgent to find new ideas for asthma prevention and treatment. In this review, we discuss the prescription, composition, formulation, and mechanism of traditional Chinese medicine monomer, traditional Chinese medicine monomer complex, single herbs, and traditional Chinese patent medicine in the treatment of asthma. We also discuss the effects of Chinese herbal medicine on asthma from the perspective of cellular endocrinology in the past decade, emphasizing on the roles as intracellular and extracellular messengers of three substances-hormones, substances secreted by pulmonary neuroendocrine cells, and neuroendocrine-related signaling protein-which provide the theoretical basis for clinical application and new drug development.

Peroxiredoxin, Senescence, and Cancer.

Peroxiredoxins are multifunctional enzymes that play a key role in protecting cells from stresses and maintaining the homeostasis of many cellular processes. Peroxiredoxins were firstly identified as antioxidant enzymes that can be found in all living organisms. Later studies demonstrated that peroxiredoxins also act as redox signaling regulators, chaperones, and proinflammatory factors and play important roles in oxidative defense, redox signaling, protein folding, cycle cell progression, DNA integrity, inflammation, and carcinogenesis. The versatility of peroxiredoxins is mainly based on their unique active center cysteine with a wide range of redox states and the ability to switch between low- and high-molecular-weight species for regulating their peroxidase and chaperone activities. Understanding the molecular mechanisms of peroxiredoxin in these processes will allow the development of new approaches to enhance longevity and to treat various cancers. In this article, we briefly review the history of peroxiredoxins, summarize recent advances in our understanding of peroxiredoxins in aging- and cancer-related biological processes, and discuss the future perspectives of using peroxiredoxins in disease diagnostics and treatments.

Metabolomics Deciphering the Potential Biomarkers of Hengqing I Prescription against Vascular Dementia.

With the aging of population, vascular dementia (VaD) seriously threatens people's health and quality of life. It is of great significance to explore biomarkers of VaD from the perspective of metabolomics and traditional Chinese medicine (TCM). Therefore, VaD was divided into kidney deficiency and blood stasis syndrome (KDBS) and non-KDBS according to TCM. Then, some patients received the treatment of Hengqing I (HQI) prescription. The urine of six groups (VaD group, normal group, KDBS group, non-KDBS group, HQI group, and control group) was detected on LC-MS/MS. Multivariate statistical analysis showed that the metabolic profiles of the three comparisons were significantly different. The top analysis-ready molecules of downregulated histamine and upregulated biotin, methionine, pantothenic acid, SAH, histidine, and kaempferol may be the most related metabolites. These putative biomarkers play an important role in the regulation of key metabolic processes linked to VaD. Additionally, pathway analysis showed aminoacyl-tRNA biosynthesis, and amino acids metabolic pathways were highly correlated with the occurrence of VaD. In this present paper, vitamins, amino acids, and their derivatives were selected as the basis for VaD diagnosis and treatment monitoring, and the significance of TCM classification and Hengqing I prescription in the treatment of VaD was discussed.

Therapeutic Effects and Metabolic Spectrum of Traditional Chinese Medicine Hengqing II Prescription on Alzheimer's Disease.

Alzheimer's disease (AD) seriously damages elders' social and daily abilities around the world. Traditional Chinese medicine (TCM), a rich drug resource bank, could help research AD. In order to explore the role of TCM in AD treatment, 86 AD patients were recruited from the hospital, then treated with Hengqing II prescription and donepezil hydrochloride. The cognitive and serum lipid levels were investigated before and after treatment. The patient's urine was collected after three months of treatment. Metabolites in the urine samples were extracted with methanol and detected on the UHPLC-MS platform. Results proved that Hengqing II can improve cognitive levels and reduce the levels of Hcy, D-D, FIB, Apo B, TC, and LDL-C compared with donepezil hydrochloride (P < 0.05). The results of multivariate statistical analysis revealed that the metabolism of HQII was significantly different compared with Control groups. A total of 66 differential metabolites were found in this comparison (50 were down-regulated and 16 were up-regulated). Four amino acid pathways and one linoleic acid pathway were found through these metabolites. After receiver operating characteristic analysis, it was suggested that palmitic acid, palmitoleic acid, linoleic acid, oleic acid, SAH, and methionine can be used as biomarkers for treating AD, while the effects of daidzein, genistein, and naringenin on the treatment of AD need to be further studied.

Heat sensitive protein-heat stable protein interaction: Synergistic enhancement in the thermal co-aggregation and gelation of lactoferrin and α-lactalbumin.

The synergistic enhancement in the thermal co-aggregation and gelation of lactoferrin (LF), a heat sensitive protein, and α-lactalbumin (ALA), a heat stable protein, was investigated at pH 7.0. Heating temperatures (70 °C and 90 °C; 30 min) and ALA concentrations (0-0.5 mM) significantly affected the structural characteristics of the resultant thermal aggregates and gels. The turbidity and size of LF-ALA thermal aggregates were increased with increasing ALA concentration; at a low total protein concentration of 0.57 mM, LF-ALA gels can be formed. The presence of ALA led to some hydrophobic residues originally located in the interior of LF to be exposed further during heating. New intermolecular disulfide bonds, mainly unstable ones, were formed between LF molecules and/or ALA molecules during co-heating. The aggregation of LF and ALA was a gradual denaturation process, accompanied by an increase in ß-sheet content and decrease in α-helix content. Random spherical aggregates with large size (1-5 µm) were observed by transmission electron microscopy, clearly confirming the nucleation and growth of LF with ALA. There existed strong rheological synergism between LF and ALA, thereby leading to a large reduction in gelation times (4-11 min) with increasing ALA concentration and heating temperature. Considering these data, LF and ALA played different and indispensable roles in thermal aggregation and gelation: LF engaged readily in thermal aggregation, while ALA mainly assisted the LF thermal aggregation. Three types of mechanisms (co-fusion, nucleation and growth) involved in the aggregation and gelation processes. In all, the data of the current study has enhanced the comprehension of heat sensitive protein-heat stable protein thermal aggregation and gelation, and may help to design LF-based new ingredients for the control of food textures and delivery systems for food and pharmaceutical applications.

Protein-neutral polysaccharide nano- and micro-biopolymer complexes fabricated by lactoferrin and oat ß-glucan: Structural characteristics and molecular interaction mechanisms.

Biopolymer complexes fabricated by proteins and neutral polysaccharides may have some specific or innovative functionalities. However, only little is known about the structural characteristics and molecular interaction mechanisms of proteins-neutral polysaccharides biopolymer complexes. Understanding these informations is of major interest for the design of new proteins-polysaccharides biopolymer complexes with specific and/or innovative functionalities. Thus, the aim of the present study was to investigate the structural characteristics and molecular interaction mechanisms of lactoferrin (LF) and oat ß-glucan (OG) with and without heat treatment at different OG concentrations (0.2, 0.5 and 0.9%, w/v). Isothermal titration calorimetry (ITC) results showed that LF and OG could interact with each other. The binding behavior between LF and OG at 25 °C was a spontaneous process, and electrostatic interactions, hydrogen bonding and van der Waals forces contributed to the LF-OG self-assembling behavior. OG concentration influenced the thermodynamic characterization of interactions between LF and OG. LF was susceptible to aggregation and thermal denaturation in the presence of OG. The increased turbidity and particle size of LF-OG complexes suggested the formation of large complexes in aqueous solution. SEM results showed that LF-OG self-assembles exhibited physically cross-linked networks at low OG concentration, while formed some spherical complexes at high OG concentration; LF-OG thermally modified complexes exhibited the honeycomb-like structures with different particle sizes in a concentration-dependent manner. Fluorescence spectroscopy results indicated that OG can change the structure of LF, leading to the exposure of Trp residues of LF molecules toward a more polar microenvironment. Raman difference spectra and circular dichroism revealed that the addition of OG could alter the secondary structure of LF, and the most noticeable changes were in the regions connected ß-structures. The apparent viscosity of LF-OG complexes were higher than that of LF or OG alone, indicating that there was synergism between LF and OG. Overall, the self-assembling complexes and thermal complexes of LF and OG can be formed at 25 °C and 90 °C, respectively. These formed LF-OG nanocomplexes and microcomplexes (both the self-assembling and thermal complexes) with unique structures can be widely used in food, pharmaceutical and cosmetic industries, which will be suitable for encapsulation and transportation of bioactive compounds, or as fat substitutes.

Structures, fabrication mechanisms, and emulsifying properties of self-assembled and spray-dried ternary complexes based on lactoferrin, oat ß-glucan and curcumin: A comparison study.

Protein-polyphenol-polysaccharide non-covalent ternary complexes possess many unique structural and functional properties. However, rare work is available to fabricate the neutral polysaccharide-based ternary complexes. Herein, the ternary complexes composed of lactoferrin (LF), oat ß-glucan (OG), and curcumin (Cur) with three binding sequences were successfully developed through self-assembly technique and spray drying technique, respectively. Spray drying could enhance the extent of the intermolecular associations among LF, OG, and Cur, leading to the formation of ternary complexes with smaller particle sizes and lower turbidities. Cur can be loaded in LF-OG complexes to form an amorphous complex through the intermolecular interactions (mainly hydrophobic interactions and hydrogen bonding). The ternary complexes can be used as potential emulsifiers to stabilize oil-in-water Pickering emulsions. The emulsifying capacity (to enhance physical stability) of the complexes was in the order as follows: the spray-dried ternary complexes > the spray-dried LF-OG complexes > the self-assembled ternary complexes > the self-assembled LF-OG complexes. The structural and functional properties (e.g., emulsifying property) of OG-based ternary complexes can be controlled by adjusting the binding sequences. These results will broaden our current understanding of protein-polyphenol-polysaccharide ternary complexes and provide more applications of OG in food, cosmetics, and pharmaceutical industries.

Effects of Pleurotus eryngii (mushroom) powder and soluble polysaccharide addition on the rheological and microstructural properties of dough.

Adding a certain proportion of Pleurotus eryngii can improve the nutritional value of wheat-flour foods and enhance the utilization of this mushroom. In this research, partial wheat flour was substituted with P. eryngii powder (PEP) or soluble polysaccharide (SPPE) at different addition levels, and the effects of PEP and SPPE on the rheological and microstructural properties of dough were investigated. Farinographic assay results suggested that PEP significantly (p < 0.05) increased the water absorption of wheat flour but decreased the development time and stability of dough significantly (p < 0.05). Furthermore, it was capable of providing weaker extensographic characteristics and harder dough with the increasing of PEP addition levels. The dynamic oscillatory tests indicated that the PEP addition approximately increased the storage (G') and loss (G″) moduli in the entire frequency range, while the tan δ roughly decreased with the increasing of PEP addition levels, which could be attributed to the low solubility and strong water-trapping capacity of the dietary fiber in PEP. Due to the good water solubility and easy formation of hydrogen bonds, the addition of SPPE had inconsistent results with the PEP addition. The inner microstructure of dough showed that the continuity of gluten networks had been disrupted by PEP and SPPE addition and then resulted in a weaker extension and harder dough. This research could provide a foundation for the application of PEP in wheat-flour foods, and PEP addition levels of 2.5%-5.0% are recommended.

Haploinsufficiency of Insm1 Impairs Postnatal Baseline ß-Cell Mass.

Baseline ß-cell mass is established during the early postnatal period when ß-cells expand. In this study, we show that heterozygous ablation of Insm1 decreases baseline ß-cell mass and subsequently impairs glucose tolerance. When exposed to a high-fat diet or on an ob/ob background, glucose intolerance was more severe in Insm1+/lacZ mice compared with Insm1+/+ mice, although no further decrease in the ß-cell mass was detected. In islets of early postnatal Insm1+/lacZ mice, the cell cycle was prolonged in ß-cells due to downregulation of the cell cycle gene Ccnd1 Although Insm1 had a low affinity for the Ccnd1 promoter compared with other binding sites, binding affinity was strongly dependent on Insm1 levels. We observed dramatically decreased binding of Insm1 to the Ccnd1 promoter after downregulation of Insm1 expression. Furthermore, downregulation of Ccnd1 resulted in a prolonged cell cycle, and overexpression of Ccnd1 rescued cell cycle abnormalities observed in Insm1-deficient ß-cells. We conclude that decreases in Insm1 interfere with ß-cell specification during the early postnatal period and impair glucose homeostasis during metabolic stress in adults. Insm1 levels are therefore a factor that can influence the development of diabetes.