Mechanism of Yanghe Pingchaun granules on airway remodeling in asthmatic rats based on IL-6/JAK2/STAT3 signaling axis

Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.

Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke

Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.

Unraveling the gut-brain axis:the impact of steroid hormones and nutrition on Parkinson's disease

This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.

Functional gastrointestinal disorders and gut-brain axis: What does the future hold?

Despite their high prevalence, lack of understanding of the exact pathophysiology of the functional gastrointestinal disorders has restricted us to symptomatic diagnostic tools and therapies. Complex mechanisms underlying the disturbances in the bidirectional communication between the gastrointestinal tract and the brain have a vital role in the pathogenesis and are key to our understanding of the disease phenomenon. Although we have come a long way in our understanding of these complex disorders with the help of studies on animals especially rodents, there need to be more studies in humans, especially to identify the therapeutic targets. This review study looks at the anatomical features of the gut-brain axis in order to discuss the different factors and underlying molecular mechanisms that may have a role in the pathogenesis of functional gastrointestinal disorders. These molecules and their receptors can be targeted in future for further studies and possible therapeutic interventions. The article also discusses the potential role of artificial intelligence and machine learning and its possible role in our understanding of these scientifically challenging disorders.

Focus on the gut-brain axis: multiple sclerosis, the intestinal barrier and the microbiome

The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.

Gut-brain axis:Focus on gut metabolites short-chain fatty acids

Emerging evidence supports that the gut microbiome,reconsidered as a new organ in the human body,can not only affect the local gut,but also communicate with the brain via multiple pathways related to neuroendocrine,immune,and neural pathways,thereby proposing the new concept of the microbiome-gut-brain(MGB)axis.Recently,the role of short-chain fatty acids(SCFAs),which are the main anaerobic fermented metabolites of the gut microbiota in the MGB axis,has garnered significant attention.SCFAs are involved in a broad range of central neurological diseases,including neurodegenerative diseases,cerebral vascular diseases,epilepsy,neuroimmune inflammatory diseases,and mood disorders.However,the underlying mechanism of SCFA-related distant organ crosstalk is yet to be elucidated.Herein,we summarize current knowledge regarding interactions between SCFAs and the MGB axis,as well as their protective effects against central neurological diseases.

Microbiota-gut-brain axis and its affect inflammatory bowel disease:Pathophysiological concepts and insights for clinicians

Despite the bi-directional interaction between gut microbiota and the brain not being fully understood,there is increasing evidence arising from animal and human studies that show how this intricate relationship may facilitate inflammatory bowel disease(IBD)pathogenesis,with consequent important implications on the possibility to improve the clinical outcomes of the diseases themselves,by acting on the different components of this system,mainly by modifying the microbiota.With the emergence of precision medicine,strategies in which patients with IBD might be categorized other than for standard gut symptom complexes could offer the opportunity to tailor therapies to individual patients.The aim of this narrative review is to elaborate on the concept of the gutbrain-microbiota axis and its clinical significance regarding IBD on the basis of recent scientific literature,and finally to focus on pharmacological therapies that could allow us to favorably modify the function of this complex system.

Healthy axis: Towards an integrated view of the gut-brain health

Despite the lack of precise mechanisms of action, a growing number of studies suggests that gut microbiota is involved in a great number of physiological functions of the human organism. In fact, the composition and the relations of intestinal microbial populations play a role, either directly or indirectly, to both the onset and development of various pathologies. In particular, the gastrointestinal tract and nervous system are closely connected by the so-called gut–brain axis, a complex bidirectional system in which the central and enteric nervous system interact with each other, also engaging endocrine, immune and neuronal circuits. This allows us to put forward new working hypotheses on the origin of some multifactorial diseases: from eating to neuropsychiatric disorders (such as autism spectrum disorders and depression) up to diabetes and tumors (such as colorectal cancer). This scenario reinforces the idea that the microbiota and its composition represent a factor, which is no longer negligible, not only in preserving what we call “health” but also in defining and thus determining it. Therefore, we propose to consider the gut-brain axis as the focus of new scientific and clinical investigation as long as the locus of possible systemic therapeutic interventions.

Gut microbiota axis:potential target of phytochemicals from plant-based foods

Food-microbiota-host interactions provide an overarching framework for understanding the function of the gut microbiota axis.Diet is a major modulator of gut microbiota.Plant-based foods are rich in phytochemicals;therefore,it is essential to assess such foods and elucidate the mechanisms underlying their action.In this review,we summarize the role of gut microbiota in the communication between the gut and the brain,liver,lung,kidney,and joints,as well as the role of the gut microbiota axis in diseases involving these organs.In addition,we assess the effects of phytochemicals from plant-based foods on the gut microbiota axis via different pathways.

Evaluation of Intraobserver and Interobserver Reliability of Mechanical Axis Alignment Measure of the Lower Limb through the Panoramic Radiograph in Patients in the Preoperative and Postoperative Periods of Total Knee Arthroplasty

Objective: To evaluate intraobserver and interobserver reliability of the measurement of the mechanical axis of the lower limb by means of the panoramic radiograph of lower limbs by physicians with different levels of medical practice. Method: A retrospective cross-sectional study with preoperative and postoperative radiographic analysis of a group of 100 patients submitted to total knee arthroplasty. Results: It was observed that there is a highly significant intraobserver and interobserver agreement (p < 0.0001), both preoperatively and postoperatively, among four observers with different training levels. Conclusion: The panoramic radiograph of the lower limbs is a reliable method for measuring the mechanical axis of the lower limb in patients submitted to total knee arthroplasty, regardless of the level of medical practice of the evaluator.

Analysis of static structural mechanics of vertical axis wind turbine with lift-drag combined starting structures

The finite element analysis was carried out for a composite vertical axis wind turbine with lift-drag combined starting structures to ensure the structure safety of a vertical axis wind turbine(VAWT).The static and modal analysis of rotor of a composite vertical axis wind turbine was conducted by using ANSYS software.The relevant contour sketch of stress and deformation was obtained.The analysis was made for static structural mechanics,modal analysis of rotor and the total deformation and vibration profile to evaluate the influence on the working capability of the rotor.The analysis results show that the various structure parameters lie in the safety range of structural mechanics in the relative standards.The analysis showing the design safe to operate the rotor of a vertical axis wind turbine.The methods used in this study can be used as a good reference for the structural mechanics′analysis of VAWTs.

Postoperative Mechanical Axis Alignment and Components Position after Conventional and Patient-Specific Total Knee Arthroplasty

Introduction: Accurate postoperative alignment and implant positioning are determinant factors for successful total knee arthroplasty (TKA). Patient-specific template (PST) is a technique that uses computer technology for the planning, deigning and production of cutting guides. This study aims to compare PST to conventional technique in terms of mechanical axis alignment and component positioning. Patients and method: 109 TKA were performed for 78 patients in 2 groups. Group A included 69 conventional TKA in 55 patients and Group B included 40 patient-specific TKA in 23 patient. Postoperative long-film X-rays were done for all patients to observe the mechanical axis, anatomical axis, lateral distal femoral mechanical angle and medial proximal tibial angle. Results: No statistically significant difference was found between the two groups regarding alignment or component positioning. Conclusion: Both techniques have shown similar results in restoring the mechanical axis and alignment after TKA. However, PST had the advantages of reduced blood loss and shorter operative time.

Research on the Unsteady Hydrodynamic Characteristics of Vertical Axis Tidal Turbine

The unsteady hydrodynamic characteristics of vertical axis tidal turbine are investigated by numerical simulation based on viscous CFD method. The starting mechanism of the turbine is revealed through analyzing the interaction of its motion and dynamics during starting process. The operating hydrodynamic characteristics of the turbine in wave-current condition are also explored by combining with the linear wave theory. According to possible magnification of the cyclic loads in the maximum power tracking control of vertical axis turbine, a novel torque control strategy is put forward, which can improve the structural characteristics significantly without effecting energy efficiency.

Mechanisms of repetitive transcranial magnetic stimulation for antidepression: Evidence from preclinical studies

This review summarizes the anti-depressant mechanisms of repetitive transcranial magnetic stimulation in preclinical studies,including anti-inflammatory effects mediated by activation of nuclear factor-E2-related factor 2 signaling pathway,anti-oxidative stress effects,enhancement of synaptic plasticity and neurogenesis via activation of the endocannabinoid system and brain derived neurotrophic factor signaling pathway,increasing the content of monoamine neurotransmitters via inhibition of Sirtuin 1/monoamine oxidase A signaling pathway,and reducing the activity of the hypothalamic-pituitary-adrenocortical axis.We also discuss the shortcomings of transcranial magnetic stimulation in preclinical studies such as inaccurate positioning,shallow depth of stimulation,and difficulty in elucidating the neural circuit mechanism up-and down-stream of the stimulation target brain region.

Numerical and Experimental Analysis of A Vertical-Axis Eccentric-disc Variable-Pitch Turbine(VEVT)

A combined experimental and numerical investigation is carried out to study the performance of a vertical-axis eccentric-disc variable-pitch turbine(VEVT).A scheme of eccentric disc pitch control mechanism based on doubleblock mechanism is proposed.The eccentric control mechanism and the deflection angle control mechanism in the pitch control structure are designed and optimized according to the functional requirements of the turbine,and the three-dimensional model of the turbine is established.Kinematics analysis of the eccentric disc pitch control mechanism is carried out.Kinematics parameters and kinematics equations which can characterize its motion characteristics are derived.Kinematics analysis and simulation are carried out,and the motion law of the corresponding mechanical system is obtained.By analyzing the force and motion of blade of VEVT,the expressions of the important parameters such as deflection angle,attack angle and energy utilization coefficient are obtained.The lateral induced velocity coefficient is acquired by momentum theorem,the hydrodynamic parameters such as energy utilization coefficient are derived,and the hydrodynamic characteristics of VEVT are also obtained.The experimental results show that the turbine has good energy capture capability at different inflow velocities of different sizes and directions,which verifies that VEVT has good self-startup performance and high energy capture efficiency.

Determinations of directions of the mean stress field in Sichuan-Yunnan region from a number of focal mechanism solutions

Based on the spatial orientation and slip direction of the fault plane solutions, we present the expression of corresponding mechanical axis tensor in geographic coordinate system, and then put forward a method for calculating average mechanical axis tensor and its eigenvalues, which involves solving the corresponding eigenequation. The method for deducing mean stress field from T, B, and P axes parameters of a number of focal mechanism solutions has been verified by inverting data of mean stress fields in Fuyun region and in Tangshan region with fitting method of slip direction, and both results are consistent. To study regional average stress field, we need to choose a population of focal mechanism solutions of earthquakes in the massifs where there are significant tectonic structures. According to the focal mechanism solutions of 256 moderate-strong earthquakes occurred in 13 seismic zones of Sichuan-Yunnan region, the quantitative analysis results of stress tensor in each seismic zone have been given. The algorithm of such method is simple and convenient, which makes the method for analyzing tectonic stress field with large amount of focal mechanism solution data become quantified.

Prion-like propagation of α-synuclein in gutbrain axis

Parkinson disease(PD) is a progressive degenerative disease of the nervous system,which is characterized by movement disorders,such as static tremor,rigidity,and bradykinesia in advanced patients.Gastrointestinal(GI) dysfunction,such as gastric dysmotility,constipation,and anorectic dysfunction,is common non-motor symptom in the early stage of PD.The progression of PD includes the degenerative loss of dopaminergic neurons and aggregation ofα-synuclein in the substantia nigra.Interestingly,both of them are also present in the enteric nervous system of PD patients.In this review,we describe the relationship between non-motor symptoms particularly GI dysfunction and the pathogenesis of PD,aiming to show the powerful evidences about the prion-like propagation of α-synuclein and support the hypothesis of gut-brain axis in PD.We then summarize the mechanism of the gut-brain axis and confirmα-synuclein as a potential target for drug design or new clinical treatment.

COVID-19 as a trigger of irritable bowel syndrome:A review of potential mechanisms

In December 2019 a novel coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),started spreading from Wuhan city of Chinese Hubei province and rapidly became a global pandemic.Clinical symptoms of the disease range from paucisymptomatic disease to a much more severe disease.Typical symptoms of the initial phase include fever and cough,with possible progression to acute respiratory distress syndrome.Gastrointestinal manifestations such as diarrhoea,vomiting and abdominal pain are reported in a considerable number of affected individuals and may be due to the SARS-CoV-2 tropism for the peptidase angiotensin receptor 2.The intestinal homeostasis and microenvironment appear to play a major role in the pathogenesis of COVID-19 and in the enhancement of the systemic inflammatory responses.Long-term consequences of COVID-19 include respiratory disturbances and other disabling manifestations,such as fatigue and psychological impairment.To date,there is a paucity of data on the gastrointestinal sequelae of SARS-CoV-2 infection.Since COVID-19 can directly or indirectly affect the gut physiology in different ways,it is plausible that functional bowel diseases may occur after the recovery because of potential pathophysiological alterations(dysbiosis,disruption of the intestinal barrier,mucosal microinflammation,post-infectious states,immune dysregulation and psychological stress).In this review we speculate that COVID-19 can trigger irritable bowel syndrome and we discuss the potential mechanisms.

Dynamic analysis of double-layer and pre-stressed multi-limb six-axis force sensor

In order to adapt to the specific task, the six-axis dynamic contact force between end-effectors of intelligent robots and working condition needs to be perceived. Therefore, the dynamic property of six-axis force sensor which is installed on the end-effectors of intelligent robots will have influence on the veracity of detection and judgment to working environment contact force by intelligent robots directly. In this paper, dynamic analysis to double-layer and pre-stressed multi-limb six-axis force sensor is conducted. First, the structure of the sensor is introduced, and the limb number is confirmed by introducing the related definitions of convex analysis. Then, based on vibration of multiple-degree-of-freedom system, a mechanical vibration simplified model of double-layer and pre-stressed multiple limb six-axis force sensor is set up. After that, movement differential equations of sensor and the response of analytical expression are deduced, and the movement differential equations is solved. Finally, taking the double-layer and pre-stressed seven limb six-axis force sensor as an example, numerical calculation and simulation of deriving result is conducted, which verify the correctness and feasibility of the theoretical analysis.

Magnetization arrangement of hard magnetic phases and mechanism of magnetization and reversal magnetization of nano-composite magnets

During the process of directional solidification,laser remelting/solidification in the layer on sintered magnets, die-upsetting of cast magnets,or die-upsetting of nano-composites,the arrangements of the easy-magnetization-axes of the hard magnetic phases(Nd2Fe14B,SmCo5 or Sm2Co17 type)in their designed directions have been studied.In Fe-Pt nano-composite magnets,attempts have been taken to promote phase transformation from disordered,soft magnetic A1 to ordered,hard magnetic L10 FePt phase at reduced temperatures.The dependence of the magnetization and reversal magnetization processes on the microstructures,involving the morphology and three critical sizes of particles of the FePt nano-composite magnets,are summarized. With the decrease of the nominal thickness of the anisotropic FePt film epitaxially grown on the single crystal MgO(001)substrate, the reversal magnetization process firstly changes from full domain wall displacement to partial magnetic wall pinning related to the morphology change,where the coercive force increases abruptly.The reversal magnetization process secondly changes from magnetic wall pinning to incoherent magnetization rotation associated with the particles being below the first critical size at which multi-domain particles turn into single domain ones,where the coercive force is still increased.And the reversal magnetization mode thirdly changes from incoherent to coherent rotation referred to the second critical size,where the increase of the coercive force keeps on.However,when the particle size decreases to approach the third critical size where the particles turn into the supperparamagnetic state,the coercive force begins to decrease due to the interplay of the size effect and the incomplete ordering induced by the size effect.Meanwhile,due to the size effect,Curie temperature of the ultra-small FePt particles reduces.