Biological factors controlling starch digestibility in human digestive system

Starch digestion rate and location in the gastrointestinal tract(GIT)are critical for human health.This review aims to present a comprehensive summary on our current understanding of physiological,biochemical,anatomical and geometrical factors of human digestive system that are related to in vivo starch digestibility.It is shown that all digestive compartments including mouth,stomach,small intestine,and large intestine play critical roles in regulating the overall starch digestion process.A proper investigation of starch digestion pattern should thus be based on the consideration of all these compartments.Main biological factors are summarized as oral mastication and salivation,gastric emptying and motility,small intestinal enzymes and motility,large intestinal resistant starch(RS)-microbiota interactions and gut-brain feedback control,as well as glucose adsorption and hormonal feedback control.However,connections among these biological factors in determining starch digestive behaviors remain elusive.This is due to the inherent complexity of human GIT anatomy,motility and biochemical conditions,as well as ethical,financial and technical issues in conducting clinical studies.Much technological and scientific efforts from both clinical studies and in vitro simulation models are required for a better understanding of in vivo starch digestion behaviors.

Research Advances in Interplay of Bursaphelenchus xylophilus and Other Key Biological Factors Related to Pine Wilt Disease

The paper separately discusses interplay of pine wood nematode and several key biological factors related to pine wilt disease, such as host trees, insect vectors, fungi, symbiotic bacteria, and natural enemy acarid, etc. By virtue of so much complicated interplay among the biological factors related to pine wilt disease which is different from other forest disease, it also points out that the further researches about pine wilt disease should focus on interplay mechanism of key biological factors to discover pathogenic mechanism, and simple and quick inspection and quarantine methods.

Surgery for Crohn's disease in the era of biologicals:A reduced need or delayed verdict?

Crohn's disease(CD) is a chronic inflammatory bowel disease that can affect the entire gastrointestinal tract.Ultimately,up to 70% of all patients will need surgery,despite optimized medical therapy.Moreover,about half of the patients will need redo-surgery because of disease recurrence.The introduction of anti-tumor necrosis factor(TNF) drugs(Infliximab in 1998) revolutionized the treatment of CD.Different randomized trials assessed the efficacy of anti-TNF treatment not only to induce,but also to maintain,steroid-free remission.Furthermore,these agents can rapidly lead to mucosal healing.This aspect is important,as it is a major predictor for long-term disease control.Subgroup analyses of responding patients seemed to suggest a reduction in the need for surgery at median-term follow up(1-3 years).However if one looks at population surveys,one does not observe any decline in the need for surgery since the introduction of Infliximab in 1998.The short follow-up term and the exclusion of patients with imminent surgical need in the randomized trials could bias the results.Only 60% of patients respond to induction of anti-TNF therapy,moreover,some patients will actually develop resistance to biologicals.Many patients are diagnosed when stenosing disease has already occurred,obviating the need for biological therapy.In a further attempt to change the actual course of the disease,top down strategies have been progressively implemented.Whether this will indeed obviate surgery for a substantial group of patients remains unclear.For the time being,surgery will still play a pivotal role in the treatment of CD.

Expression of hypoxia-inducible factor 1 alpha and oligodendrocyte lineage gene-1 in cultured brain slices after oxygen-glucose deprivation

Oligodendrocyte lineage gene-1 expressed in oligodendrocytes may trigger the repair of neuronal myelin impairment, and play a crucial role in myelin repair. Hypoxia-inducible factor la, a transcription factor, is of great significance in premature infants with hypoxic-ischemic brain damage There is little evidence of direct regulatory effects of hypoxia-inducible factor le on oligodendrocyte lineage gene-l. In this study, brain slices of Sprague-Dawley rats were cultured and subjected to oxygen-glucose deprivation. Then, slices were transfected with hypoxia-inducible factor la or oligodendrocyte lineage gene-1. The expression levels of hypoxia-inducible factor la and oligodendrocyte lineage gene-1 were significantly up-regulated in rat brains prior to transfection, as detected by immunohistochemical staining. Eight hours after transfection of slices with hypoxia-inducible factor la, oligodendrocyte lineage gene-1 expression was upregulated, and reached a peak 24 hours after transfection. Oligodendrocyte lineage gene-1 transfection induced no significant differences in hypoxia-inducible factor la levels in rat brain tissues with oxygen-glucose deprivation. These experimental findings indicate that hypoxia-inducible factor la can regulate oligodendrocyte lineage gene-1 expression in hypoxic brain tissue, thus repairing the neural impairment.

A Preliminary Study on Principle of Etiology Mechanism

Based on the inspiration from Hetu and Luoshu,a principle diagram of pathogenicity of pathogenic factors was established.Accordingly,the inner correlations between pathogenic factor type and biological factors,and between pathogenic factors and host were analyzed.Mechanism of pathogenesis was discussed with five representative cases.The result indicated that effect of biological factors on host could be proved only with the performance of internalization conditions of biological factor and host.The reciprocal transformation between biological factors and pathogenic factors was decided by interaction and state of co-existed factors and host.The results suggested that it is a better and attractive choice to regulate and optimize the host’s state in practice than direct elimination of pathogens with antibiotics.

Calpain mediated cisplatin-induced ototoxicity in mice

Ototoxic drug-induced apoptosis of inner ear cells has been shown to be associated with calpain expression. Cisplatin has severe ototoxicity, and can induce cochlear cell apoptosis. This study assumed that cisplatin activated calpain expression in apoptotic cochlear cells. A mouse model of cisplatin-induced ototoxicity was established by intraperitoneal injection with cisplatin （2.5, 3.5, 4.5, 5.5 mg/kg）. Immunofluorescence staining, image analysis and western blotting were used to detect the expression of calpain 1 and calpain 2 in the mouse cochlea. At the same time, the auditory brainstem response was measured to observe the change in hearing. Results revealed that after intraperitoneal injection with cisplatin for 5 days, the auditory brainstem response threshold shifts increased in mice. Calpain 1 and calpain 2 expression significantly increased in outer hair cells, the spiral ganglion and stria vascularis. Calpain 2 protein expression markedly increased with an increased dose of cisplatin. Results suggested that calpain 1 and calpain 2 mediated cisplatin-induced ototoxicity in BALB/c mice. During this process, calpain 2 plays a leading role.

Activin A prevents neuron-like PC12 cell apoptosis after oxygen-glucose deprivation

In this study, PC12 cells were induced to differentiate into neuron-like cells using nerve growth factor, and were subjected to oxygen-glucose deprivation. Cells were treated with 0, 10, 20, 30, 50, 100 ng/mL exogenous Activin A. The 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl tetrazolium bromide assay and Hoechst 33324 staining showed that the survival percentage of PC12 cells significantly decreased and the rate of apoptosis significantly increased after oxygen-glucose deprivation. Exogenous Activin A significantly increased the survival percentage of PC12 cells in a dose-dependent manner. Reverse transcription-PCR results revealed a significant increase in Activin receptor IIA, Smad3 and Smad4 mRNA levels, which are key sites in the Activin A/Smads signaling pathway, in neuron-like cells subjected to oxygen-glucose deprivation, while mRNA expression of the apoptosis-regulation gene caspase-3 decreased. Our experimental findings indicate that exogenous Activin A plays an anti-apoptotic role and protects neurons by means of activating the Activin A/Smads signaling pathway.

Inflammatory pathways of importance for management of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a group of chronic disorders of the gastrointestinal tract comprising Crohn’s disease (CD) and ulcerative colitis (UC). Their etiologies are unknown, but they are characterised by an imbalanced production of pro-inflammatory mediators, e.g., tumor necrosis factor (TNF)-α, as well as increased recruitment of leukocytes to the site of inflammation. Advantages in understanding the role of the inflammatory pathways in IBD and an inadequate response to conventional therapy in a large portion of patients, has over the last two decades lead to new therapies which includes the TNF inhibitors (TNFi), designed to target and neutralise the effect of TNF-α. TNFi have shown to be efficient in treating moderate to severe CD and UC. However, convenient alternative therapeutics targeting other immune pathways are needed for patients with IBD refractory to conventional therapy including TNFi. Indeed, several therapeutics are currently under development, and have shown success in clinical trials. These include antibodies targeting and neutralising interleukin-12/23, small pharmacologic Janus kinase inhibitors designed to block intracellular signaling of several pro-inflammatory cytokines, antibodies targeting integrins, and small anti-adhesion molecules that block adhesion between leukocytes and the intestinal vascular endothelium, reducing their infiltration into the inflamed mucosa. In this review we have elucidated the major signaling pathways of clinical importance for IBD therapy and highlighted the new promising therapies available. As stated in this paper several new treatment options are under development for the treatment of CD and UC, however, no drug fits all patients. Hence, optimisations of treatment regimens are warranted for the benefit of the patients either through biomarker establishment or other rationales to maximise the effect of the broad range of mode-of-actions of the present and future drugs in IBD.

Construction of a eukaryotic expression plasmid for human retina-derived neurotrophin-3

Neurotrophin-3 （NT-3） can promote the repair of central nervous system and retinal damage. In previous reports, NT-3 has been expressed by viral vectors. However, plasmid vectors have a safer profile compared with viral vectors in clinical studies. This study recombined amplified human retinal NT-3 with a eukaryotic expression plasmid containing green fluorescent protein （GFP） to construct an NT-3 expression plasmid, pEGFP-N1-NT-3. The transfection efficiency 48 hours after pEGFP-N1-NT-3 transfection to 293T cells was 50.06 ＋ 2.78%. Abundant NTo3-GFP was expressed in 293T cells as observed by fluorescence microscopy, suggesting the construct pEGFP-N1-NT-3 effectively expressed and secreted NT-3-GFP. Secretory vesicles containing NT-3-GFP were observed in a constant location in cells by laser scan confocal microscopy, indicating the expression and secretion processes of NT-3 in eukaryotic cells were in accordance with the physical synthesis processes of secreted proteins. Western blot assay showed that pro-NTo3-GFP had a molecular weight of 56 kDa, further confirming NT-3-GFP expression. At 48 hours after transfection, the concentration of NT-3 in culture medium was 22.3 ng/mL, suggesting NT-3 produced by pEGFP-N1-NT-3 was efficiently secreted. This study constructed a human retinal-derived NT-3 eukaryotic expression plasmid that efficiently expressed and secreted NT-3.

Monocyte chemoattractant protein-1, transforming growth factor-β1, nerve growth factor, resistin and hyaluronic acid as serum markers：comparison between recurrent acute and chronic pancreatitis

BACKGROUND： Diagnostic parameters that can predict the presence of chronic pancreatitis（CP） in patients with recurrent pain due to pancreatitis would help to direct appropriate therapy. This study aimed to compare the serum levels of monocyte chemoattractant protein-1（MCP-1）, transforming growth factor-β1（TGF-β1）, nerve growth factor（NGF）, resistin and hyaluronic acid（HA） in patients with recurrent acute pancreatitis（RAP） and CP to assess their ability to differentiate the two conditions.METHODS： Levels of serum markers assessed by enzymelinked immunosorbent assay（ELISA） were prospectively compared in consecutive patients with RAP, CP and in controls and stepwise discriminant analysis was performed to identify the markers differentiating RAP from CP.RESULTS： One hundred and thirteen consecutive patients（RAP=32, CP=81） and 78 healthy controls were prospectively enrolled. The mean（SD） age of the patients was 32.0（14.0）years; 89（78.8%） were male. All markers were significantly higher in CP patients than in the controls（P〈0.001）; MCP-1NGF and HA were significantly higher in RAP patients than in the controls（P〈0.001）. Stepwise discriminant analysis showed significant difference（P=0.002） between RAP and CP for resistin with an accuracy of 61.9%, discriminant scores of ≤-0.479 and ≥0.189 indicating RAP and CP, respectively. The other markers had no differential value between RAP and CP.CONCLUSION： Serum resistin is a promising marker to differentiate between RAP and CP and needs validation in future studies, especially in those with early CP.

Minocycline inhibits the production of the precursor form of nerve growth factor by retinal microglial cells

A rat model of acute ocular hypertension was established by enhancing the perfusion of balanced salt solution in the anterior chamber of the right eye. Minocycline （90 mg/kg） was administered intraperitoneally into rats immediately after the operation for 3 consecutive days. Immunofluorescence, western blot assay and PCR detection revealed that the expression of the precursor form of nerve growth factor, nerve growth factor and the p75 neurotrophin receptor, and the mRNA expression of nerve growth factor and the p75 neurotrophin receptor, increased after acute ocular hypertension. The number of double-labeled CD11B- and precursor form of nerve growth factor-positive cells, glial fibrillary acidic protein- and p75 neurotrophin receptor-positive cells glial fibrillary acidic protein- and caspase-3-positive cells in the retina markedly increased after acute ocular hypertension. The above-described expression decreased after minocycline treatment. These results suggested that minocycline inhibited the increased expression of the precursor form of nerve growth factor in microglia, the p75 neurotrophin receptor in astroglia, and protected cells from apoptosis.

Optimization of reporter gene assay:several factors influencing detection of promoter activity

Background Promoter analysis is currently applied to detect the expression of the targeted gene in studies of signal transduction and transcriptional regulation. As a reporter gene, luciferase plays an important role and has been used widely in the promoter assay. Methods Human embryonic lung fibroblast cells （2BS）, HeLa cells and MCF-7 cells were transfected with various genes embedded by lipofectamine. This study determined vadous factors that affect promoter activity determination, such as the selection of the reporter genes and internal references, the dose and the type of the vectors carrying the transcription factors, the host cells and the instruments. Results The sensitivity of the luciferase assay was much higher than that of enhanced green fluorescence protein （EGFP）. Moreover, promoter activity is increased in a dose-related manner only in certain ranges outside of which the results may be reversed and the promoter activity is related to the expression vector which is carrying the cDNA. Otherwise, the length of the promoter, internal references and the host cell can also influence the promoter activity. Conclusions To detect the promoter activity accurately, a few factors including dose, vector, length and host cell which influence reporter gene assay aforementioned should be considered.

Study on Integral Dissolution Model Based on Biological Potency for Compound Chinese Materia Medica

Objective To investigate the integral dissolution model based on biological potency in order to evaluate the dissolution of Compound Chinese materia medica（CCMM） in vitro. Methods The contents of paeoniflorin, phillyrin, ginsenoside Rg1, and adenosine of ten batches of Compound Biejia Ruangan Tablet（CBRT） were determined at different times. The self-defined weighting coefficient based on the contents has been created to establish the integral dissolution model. In addition, the biological potency of CBRT was measured by MTT assay. Then, the f2 similar factor was used to evaluate the similarity of the batches. Results Compared with batch a, some batches’ f2 values of paeoniflorin and adenosine were less than 50, while f2 values of ginsenoside Rg1, phillyrin, and integral component were more than 50. Likewise, ginsenoside Rg1, phillyrin, and integral component were all in good correlation with biological dissolution. Conclusion The results of the integral dissolution based on biological test of CBRT demonstrate that the bioassay method may be a promising supplement for its quality evaluation.

A mini-review on how the COVID-19 pandemic affected intertemporal choice

The coronavirus disease(COVID-19)has extremely harmful effects on individual lifestyles,and at present,people must make financial or survival decisions under the profound changes frequently.Although it has been reported that COVID-19 changed decision-making patterns,the underlying mechanisms remained unclear.This mini-review focuses on the impact of the COVID-19 pandemic on in-tertemporal choice,and potential psychological,biological,and social factors that mediate this relationship.A search of the Web of Science electronic database yielded 23 studies.The results showed that under the COVID-19 pandemic,people tended to choose immediate and smaller rewards,and became less patient.In particular,people with negative emotions,in a worse condition of physical health,or who did not comply with their government restriction rules tended to become more"short-sighted"in behavioral terms.Future studies should examine more longitudinal and cross-cultural research to give a broad view about the decision-making change under the COVID-19 pandemic.