Rancid odors can trigger retching and aversion in humans that prevent consumption of spoiled food, and consequently metabolic dysregulation, but the underlying neural mechanisms remain unclear. Here, we show that exposure to 2-methylbutyric acid (2MBA) odor triggers such defensive responses in male mice, mediated by a nose-to-brain axis. 2MBA perception in olfactory epithelium activates neurons in olfactory bulb (OB) projecting to glutamatergic neurons in anterior piriform cortex (aPirGlu), which in turn project to either the mediodorsal thalamic nucleus (MD), which innervates respiratory muscles to drive retching-like behaviors, or project to the nucleus accumbens (NAc) to drive aversion. Artificial inhibition of the nose→OB→aPir→MDGlu→respiratory muscles circuit diminishes retching-like behaviors, but not aversion, while inhibiting the nose→OB→aPir→NAc circuit diminishes aversion, but not retching-like behaviors. These findings thus establish a nose-to-brain axis for rancid odor-triggered retching and aversion in male mice, advancing our understanding of sensory-motor integration and whole-body neural bases of defensive responses to odor. Rancid odors trigger retching and aversion. Here, authors show a nose-to-brain axis whereby such odors activate olfactory-piriform circuits that diverge to mediodorsal thalamic nucleus and nucleus accumbens to mediate retching-like behavior and aversion.

BackgroundAs markers of inflammation and oxidative stress, immune cells and high-density lipoprotein cholesterol (HDL-c) derivative markers, such as the monocyte to HDL-c ratio (MHR) and lymphocyte to HDL-c ratio (LHR), have been widely utilized in clinical practice. This study aims to elucidate the roles of MHR and LHR in the impact of hypertriglyceridemia (HTG) on hyperuricemia (HUA) in diabetes mellitus (DM) from a clinical perspective.MethodsThe final analysis included 976 individuals with DM. The correlations of MHR and LHR with HTG and HUA were evaluated using the restricted cubic splines (RCS) and binomial logistic regression analysis. Additionally, the mediating role of MHR and LHR in the effect of HTG on HUA was assessed using an adjusted mediation analysis.ResultsParticipants in the HTG and HUA groups demonstrated significantly elevated MHR and LHR levels (All P < 0.001). After applying adjustment for potential confounders, MHR remained a significant association with HTG and HUA, with ORs (95% CI) of 1.59 (1.43-1.77) for HTG and 1.13 (1.04-1.23) for HUA (both P < 0.05). Similarly, LHR exhibited independent correlations with HTG and HUA, yielding ORs (95% CI) of 2.34 (1.91-2.88) for HTG and 1.63 (1.33-2.00) for HUA. In the RCS analysis, MHR exhibited a nonlinear relationship with both HTG (P for nonlinear = 0.001) and HUA (P for nonlinear < 0.001). Conversely, LHR demonstrated a linear correlation with HTG (P for nonlinear = 0.062) and HUA (P for nonlinear = 0.268). Furthermore, the adjusted mediation analysis revealed that both MHR and LHR partially mediated the effect of HTG on HUA, accounting for the mediated proportion of 20.51% and 37.17%, respectively.ConclusionBoth MHR and LHR partially mediate the effect of HTG on HUA, indicating the vital effect of inflammation and oxidative stress in this association.

This study aimed to observe the effect of electroacupuncture (EA) on the spatial memory of diabetic rats and to determine the expression of synaptic plasticity-related proteins in the dentate gyrus (DG), thereby exploring the potential therapeutic mechanism of EA. We established a diabetic rat model using streptozotocin and treated the rats with EA at the acupoints ST36 and EXB3. We examined fasting blood glucose (FBG) levels, spatial memory, neuronal pathological changes, and protein and mRNA expression of postsynaptic density protein-95 (PSD95) and synapsin I in the DG. EA treatment significantly reduced FBG levels in diabetic model rats, significantly improved spatial memory, increased the number of DG neurons, and upregulated the expression of the synaptic plasticity-related proteins PSD95 and synapsin I. Study findings suggest that EA treatment may improve spatial memory, with its potential mechanism being related to reducing FBG levels, increasing the number of DG neurons, and upregulating the expression of synaptic plasticity-related proteins PSD95 and synapsin I.

A variety of studies show the involvement of acid-sensing ion channel 1a (ASIC1a) in the modulation of stress, however, the precise underlying mechanisms remain unclear. In this study, we provided evidence that ASIC1a, the Ca2+-permeable cationic ion channel, was co-expressed with corticotropin-releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN). Downregulation of ASIC1a in the PVN CRH neuron decreased the hypothalamic-pituitary-adrenal (HPA) axis activity, which further ameliorated anxiety- and depression-related behaviors by reducing CRH neuron activity. In vitro, activation of ASIC1a elevated the intracellular Ca2+ concentration and promoted the expression of CRH by activating Ca2+/CaMKII/c-Fos signaling pathways. This study reveals a novel mechanism of the modulation of negative mood by ASIC1a and suggests a potential novel therapeutic target for stress-related diseases.

Painful diabetic neuropathy (PDN) is a debilitating complication of diabetes, yet its central nervous system pathogenesis remains poorly understood. We investigated transcriptomic alterations in the central amygdala (CeA) in a diabetic rat model exhibiting neuropathic pain behavior. Male Sprague-Dawley rats were intraperitoneally injected a single dose of streptozotocin to induce diabetes. Six weeks following administration, the development of neuropathic pain was confirmed by the von Frey filament test. Subsequently, RNA sequencing of the CeA tissues was performed. This dataset provides a transcriptomic resource of the CeA in a rat model of diabetes-associated neuropathic pain, which is publicly available to facilitate research into the central mechanisms of PDN.

BACKGROUND: Circular RNAs (circRNAs) constitute a recently discovered class of evolutionarily conserved and robust regulatory RNAs. Their potential as diagnostic biomarkers and therapeutic targets for various diseases is a subject of growing interest. Nevertheless, the precise regulatory roles and underlying mechanisms of circRNAs in the context of kidney stone formation remain largely unexplored. METHODS: Utilizing RNA high-throughput sequencing technology and quantitative real-time polymerase chain reaction (qRT-PCR), we conducted a comprehensive screen for calcium oxalate crystals (CaOx)-induced differential expression of circular RNA (circRSPRY1) in the human renal tubular epithelial cells (HK-2) kidney injury model. Subsequently, we employed a combination of RNA and protein expression analyses, luciferase activity assays, and immunohistochemistry (IHC) to elucidate the regulatory role of circRSPRY1 in targeting the miR-21-5p/PTEN axis, influencing the processes of necroptosis and apoptogenesis. RESULTS: In this investigation, we observed a notable downregulation of circRSPRY1 expression in both the CaOx-stimulated HK-2 renal tubular epithelial cell injury model and a glyoxalate-induced mouse model of renal calcinosis. Notably, overexpressing circRSPRY1 led to reduced crystalline deposition in our in vitro model. Mechanistically, circRSPRY1 overexpression was associated with the downregulation of cleaved-caspase-8, p-MLKL, P-RIPK1, and P-PIPK3 levels, consequently inhibiting necrotic apoptosis. Furthermore, circRSPRY1 appeared to act as a miR-21-5p sponge, resulting in reduced miR-21-5p availability for PTEN binding and, subsequently, increased PTEN expression, thus impeding the progression of necrotic apoptosis and kidney injury. Additionally, inhibiting miR-21-5p levels demonstrated the ability to suppress necrotic apoptosis in renal calcinosis by downregulating the PTEN/MLKL pathway. CONCLUSION: Our findings suggest that circRSPRY1 represents a novel candidate circRNA implicated in the pathogenesis of kidney stones. circRSPRY1 acts as a sponge, sequestering miR-21-5p to modulate PTEN expression, thereby regulating necrotic apoptosis and contributing to the formation of calcium oxalate stones.

Neuropathic pain associated with central sensitization is common in diabetic patients, but the underlying mechanisms remain unclear. Here, a proteomics screen identified a previously uncharacterized protein, galectin-related protein (LGALSL), which was significantly upregulated in cerebrospinal fluid and extracellular fluid of the anterior cingulate cortex (ACC) in diabetes-related neuropathic pain (DNP) model rats. Exogenous LGALSL administration reduced mechanical nociceptive thresholds by activating glutamatergic neurons in the ACC (ACCGlu). Chemogenetic manipulations and functional assays revealed that neuron-derived LGALSL directly binds to vimentin on ACC astrocytes, activating those astrocytes. These activated astrocytes subsequently maintain ACCGlu hypersensitivity, driving mechanical hypersensitivity in diabetic rats. Blocking LGALSL-vimentin interactions with a synthetic peptide alleviated LGALSL-induced mechanical hypersensitivity. This study establishes LGALSL-dependent astrocyte-mediated hyperactivation of ACCGlu neurons as a new pathological mechanism of neuropathic pain in diabetes.

Effective treatment strategies for diabetes-related pain are limited due to its complex pathogenesis, particularly brain mechanisms underlying this disease. The acid-sensing ion channel 1a (ASIC1a) emerges as a key player in the development and treatment of various types of pain. Here, we investigated the role of ASIC1a in diabetes-related pain and its molecular mechanisms in the anterior cingulate cortex (ACC). Our findings demonstrate that the up-regulation of ASIC1a expression drives enhanced activity of excitatory glutamatergic neurons in the ACC (ACCGlu), promoting the development of pain hypersensitivity in streptozotocin (STZ)-induced diabetic male mice. Pharmacological inhibition and genetic knockout of ASIC1a in ACCGlu neurons significantly reduced neuronal activity and alleviated mechanical and thermal pain sensitizations in STZ-induced diabetes. Furthermore, increased levels of TNF-α in the ACC up-regulated ASIC1a through triggering NF-κB pathways, which led to the development of diabetes-related pain. Notably, the clinically used medication, infliximab, exhibited therapeutic effects on diabetes-related pain via its influencing on TNF-α/NF-κB/ASIC1a pathway in STZ mice. Collectively, this study identifies ASIC1a as a potential therapeutic target for diabetes-related pain, and the neutralization of TNF-α leads to pain relief through the TNF-α/NF-κB/ASIC1a pathway in the ACC. These findings hold promise for the development of the new clinical therapeutic strategies for diabetes-related pain.

Rapid glucose supply is crucial for animal survival during stress response. How the timescale of stress-induced glucose release precisely controlled by hypothalamic corticotropin-releasing hormone (CRH) neurons remains unclear. Here, we show that stress-induced hyperglycemia can be divided into at least two stages in male mice: the first fast stage is mediated by hypothalamus (paraventricular to ventromedial hypothalamus)-sympathetic (raphe pallidus nucleus to intermediolateral nucleus)-liver (HSL) axis activity; the second delayed stage is mediated by adrenal activity. Blocking the activity of HSL axis impairs predatory evoked flight responses, indicating that the HSL pathway activity is necessary for stress coping. We further reveal the intracellular signal cascade for CRH signal in the hypothalamus, which is mediated by GABAA receptor β3 subunit phosphorylation at S408/409, results in prevention of GABAA receptor membrane recruitment. Thus, we uncovered the precise timescale of glucose supply during stress which is mediated by adrenal independent HSL and adrenal dependent pathway respectively.

The commencement of kidney stone formation involves a crucial initial phase characterized by injury to renal tubular cells caused by calcium oxalate (CaOx). Dioscin (Dio) has been acknowledged for its potent anti-inflammation and anti-apoptotic properties; nevertheless, the impact and underlying Investigation into the molecular basis underlying the action of Dioscin in mitigating inflammation and apoptotic induced by exposure to calcium oxalate crystals in renal tissues remain unexplored. To comprehend the precise mechanism of Dioscin in the treatment of crystalline nephropathy, we conducted experiments utilizing a murine model of CaOx crystal deposition, induced by intraperitoneal administration of glyoxylate. An in vitro model was constructed using HK-2 cells exposed to calcium oxalate monohydrate (COM). To evaluate the effect of Dioscin on calcium oxalate crystal deposition by ROS assay, Western blotting, immunohistochemistry, Periodic Acid-Schiff staining (PAS) staining, hematoxylin–eosin (H E) staining. Using network pharmacology and molecular docking methods, we explored the molecular mechanism of Dioscin in the treatment of CaOx-induced renal tubular epithelial cell injury. Subsequently, we conducted experiments to verify our findings. We observed a significant protective effect of Dioscin treatment against kidney oxidative stress and inflammation induced by CaOx. Then we predicted through network pharmacology that Dioscin exerts its anti-apoptotic effect through the NF-kappa B signaling pathway. Then we verified in vitro and in vivo that administration of Dioscin can alleviate the elevation of TLR4 and activation of the NF-kappa B signaling pathway induced by calcium oxalate, as well as attenuate renal apoptosis. Instead, the beneficial impact of this protection of Dioscin was reversed after overexpression of the TLR4. Dioscin has the potential to alleviate the activation of the NF-kappa B signaling pathway through TLR4, thereby exerting anti-inflammatory and anti-apoptotic effects. This study provides new ideas for the prevention and treatment of kidney stones.

Background Phosphodiesterases (PDEs) are enzymes that catalyze the hydrolysis of cyclic adenosine monophosphate AMP (cAMP) and/or cyclic guanosine monophosphate (cGMP). PDE inhibitors can mitigate chronic pain and depression when these disorders occur individually; however, there is limited understanding of their role in concurrent chronic pain and depression. We aimed to evaluate the mechanisms of action of PDE using two mouse models of concurrent chronic pain and depression. Methods C57BL/6J mice were subjected to partial sciatic nerve ligation (PSNL) to induce chronic neuropathic pain or injected with complete Freund's adjuvant (CFA) to induce inflammatory pain, and both animals showed depression-like behavior. First, we determined the change in PDE expression in both animal models. Next, we determined the effect of PDE7 inhibitor BRL50481 or hippocampal PDE7A knockdown on PSNL- or CFA-induced chronic pain and depression-like behavior. We also investigated the role of cAMP-protein kinase A (PKA)-cAMP response element binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling and neuroinflammation in the effect of PDE7A inhibition on PSNL- or CFA-induced chronic pain and depression-like behavior. Results This induction of chronic pain and depression in the two animal models upregulated hippocampal PDE7A. Oral administration of PDE7 inhibitor, BRL50481, or hippocampal PDE7A knockdown significantly reduced mechanical hypersensitivity and depression-like behavior. Hippocampal PDE7 inhibition reversed PSNL- or CFA-induced downregulation of cAMP and BDNF and the phosphorylation of PKA, CREB and p65. cAMP agonist forskolin, reversed these changes and caused milder behavioral symptoms of pain and depression. BRL50481 reversed neuroinflammation in the hippocampus in PSNL mice. Conclusions Hippocampal PDE7A mediated concurrent chronic pain and depression in both mouse models by inhibiting cAMP-PKA-CREB-BDNF signaling Inhibiting PDE7A or activating cAMP-PKA-CREB-BDNF signaling are potential strategies to treat concurrent chronic pain and depression.

Purpose: Our objective is to investigate the potential involvement of free triiodothyronine (FT3), a key bioactive compound found in thyroid hormones (THs) in the pathogenesis of diabetic peripheral neuropathy (DPN) in patients diagnosed with type 2 diabetes mellitus (T2DM). Patients and Methods: A total of 121 T2DM patients were recruited. And then, they were divided into the control group and the DPN group. Clinical parameters were collected for each patient. Additionally, nerve conduction velocity was tested using neurophysiological methods. Correlation and regression analyses were employed to examine the relationship between the concentrations of FT3 and DPN. Results: Compared to 57 patients without DPN, 64 patients with DPN showed increased HbA1c and low-density lipoprotein cholesterol (LDL-C) levels (P=0.001 and 0.042), as well as decreased concentrations of FT3 (P=0.042). Additionally, FT3 levels are positively associated with the motor and sensory fibers conduction velocity of the Ulnar nerve, as well as the motor conduction velocity of the Tibial nerve, with (R=0.205, P=0.025; R=0.191, P=0.038; R=0.220, p=0.016) or without (R=0.257, P=0.004; R=0.227, P=0.012; R=0.227, p=0.012) adjustment for HbA1c and LDL-C. Furthermore, multiple linear regression analysis suggests that decreased FT3 levels may influence the motor and sensory fibers conduction velocity of the Ulnar nerve ((3=0.795, P=0.025 and (3=0.909, P=0.038), as well as the motor conduction velocity of the Tibial nerve ((3=0.727, P=0.016). Moreover, our study demonstrated that decreased FT3 levels are one of the risk factors for DPN in T2DM patients, as determined by binary logistic regression analysis (OR=0.542, P=0.022). Conclusion: Lower concentrations of FT3 are one of the risk factors for DPN in patients with T2DM. Additionally, decreased FT3 levels may influence peripheral neuropathy, particularly affecting the motor and sensory fibers conduction velocity of the ulnar nerve, as well as the motor fiber conduction velocity of the tibial nerve.

It remains unknown whether the Chinese tree shrew, regarded as the closest sister of primate, has evolved a dorsolateral prefrontal cortex (dlPFC) comparable with primates that is characterized by a fourth layer (L4) enriched with granular cells and reciprocal connections with the mediodorsal nucleus (MD). Here, we reported that following AAV-hSyn-EGFP expression in the MD neurons, the fluorescence micro-optical sectioning tomography revealed their projection trajectories and targeted brain areas, such as the hippocampus, the corpus striatum, and the dlPFC. Cre-dependent transsynaptic viral tracing identified the MD projection terminals that targeted the L4 of the dlPFC, in which the presence of granular cells was confirmed via cytoarchitectural studies by using the Nissl, Golgi, and vGlut2 stainings. Additionally, the L5/6 of the dlPFC projected back to the MD. These results suggest that the tree shrew has evolved a primate-like dlPFC which can serve as an alternative for studying cognition-related functions of the dlPFC.

Heterotopic ossification (HO), often arising in response to traumatic challenges, results from the aberrant osteochondral differentiation of mesenchymal stem cells (MSCs). Nevertheless, the impact of trauma-induced inflammatory exposure on MSC fate determination remains ambiguous. In this study, the cellular diversity within inflammatory lesions is elucidated, comprising MSCs and several innate and adaptive immune cells. It is observed that quiescent MSCs transition into cycling MSCs, subsequently giving rise to chondrogenic (cMSC) and/or osteogenic (oMSC) lineages within the inflammatory microenvironment following muscle or tendon injuries, as revealed through single-cell RNA sequencing (scRNA-seq), spatial transcriptome and lineage tracing analysis. Moreover, these investigations demonstrate that neutrophils and natural killer (NK) cells enhance transition of quiescent MSCs into cycling MSCs, which is also controlled by M1 macrophages, a subpopulation of macrophages can also stimulate cMSC and oMSC production from cycling MSCs. Additionally, M2 macrophages, CD4+ and CD8+ T lymphocytes are found to promote chondrogenesis. Further analysis demonstrates that immune cells promotes the activation of signaling transducers and activators of transcription (STAT) pathway and phosphoinositide 3 (PI3K)/protein kinase B (AKT) pathway in MSC proliferation and osteochondral progenitors' production, respectively. These findings highlight the dynamics of MSC fate within the inflammatory lesion and unveil the molecular landscape of osteoimmunological interactions, which holds promise for advancing HO treatment.

Background Phosphodiesterases (PDEs) are enzymes that catalyze the hydrolysis of cyclic adenosine monophosphate AMP (cAMP) and/or cyclic guanosine monophosphate (cGMP). PDE inhibitors can mitigate chronic pain and depression when these disorders occur individually; however, there is limited understanding of their role in concurrent chronic pain and depression. We aimed to evaluate the mechanisms of action of PDE using 2 mouse models of concurrent chronic pain and depression.Methods C57BL/6J mice were subjected to partial sciatic nerve ligation (PSNL) to induce chronic neuropathic pain or injected with complete Freund's adjuvant (CFA) to induce inflammatory pain, and both animals showed depression-like behavior. First, we determined the change in PDE expression in both animal models. Next, we determined the effect of PDE7 inhibitor BRL50481 or hippocampal PDE7A knockdown on PSNL- or CFA-induced chronic pain and depression-like behavior. We also investigated the role of cAMP-protein kinase A (PKA)-cAMP response element binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling and neuroinflammation in the effect of PDE7A inhibition on PSNL- or CFA-induced chronic pain and depression-like behavior.Results This induction of chronic pain and depression in the 2 animal models upregulated hippocampal PDE7A. Oral administration of PDE7 inhibitor, BRL50481, or hippocampal PDE7A knockdown significantly reduced mechanical hypersensitivity and depression-like behavior. Hippocampal PDE7 inhibition reversed PSNL- or CFA-induced downregulation of cAMP and BDNF and the phosphorylation of PKA, CREB, and p65. cAMP agonist forskolin reversed these changes and caused milder behavioral symptoms of pain and depression. BRL50481 reversed neuroinflammation in the hippocampus in PSNL mice.Conclusions Hippocampal PDE7A mediated concurrent chronic pain and depression in both mouse models by inhibiting cAMP-PKA-CREB-BDNF signaling. Inhibiting PDE7A or activating cAMP-PKA-CREB-BDNF signaling are potential strategies to treat concurrent chronic pain and depression.

Objective: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 inhibitors (DPP-4i) profoundly affect the gastrointestinal motor system, which may increase the incidence of inadequate bowel cleaning and gastrointestinal symptoms. Hence, this observational study mainly aimed to assess the influence of GLP-1 RAs liraglutide and DPP-4i sitagliptin on bowel preparation in type 2 diabetes (T2DM). Method: This observational study consecutively enrolled T2DM scheduled for a colonoscopy. Participants were prospectively separated into the liraglutide group (n = 120), sitagliptin group (n = 120), and control group (n = 120) based on the current hypoglycemic regimen. 3L split-dose polyethylene glycol regimens were used for bowel preparation. Experienced gastrointestinal endoscopists conducted colonoscopies. Lawrance Bowel-Preparation Tolerability Questionnaire and Boston Bowel Preparation Scale (BBPS) were conducted to assess bowel cleaning quality, tolerability, and safety. Results: The incidence of inadequate bowel cleaning was 17.5% in the liraglutide group, 20.5% in the sitagliptin group, and 21.7% in the control group. The difference among the three groups was not statistically significant (p = 0.927). Meanwhile, there were no significant differences in the mean BBPS, cecal intubation time, and polyp-detecting rates among the three groups (all p > 0.0.05). Nausea, vomiting, and bloating scores were increased in the liraglutide group compared with the other two groups (p < 0.05), whereas most were mild or very mild. Subgroup analyses showed that the incidence of inadequate bowel cleaning in T2DM with diabetic peripheral neuropathy (DPN) was increased in the liraglutide group compared with the sitagliptin group (61.3% vs. 32.1%, p = 0.022) and control group (61.3% vs. 32.8%, p = 0.025). Conclusion: GLP-1RA liraglutide or DPP-4i sitagliptin did not significantly increase the incidence of inadequate bowel cleaning and gastrointestinal symptoms during bowel preparation. Liraglutide may increase the incidence of inadequate bowel preparation in patients with DPN. This study reveal that more attention and aggressive bowel preparation regimens should be given to the T2DM with DPN. Clinical Trial Registration: (https://www.chictr.org.cn/index.aspx), identifier (ChiCTR2200056148).

Withdrawal from chronic opioid use often causes hypodopaminergic states and negative affect, which may drive relapse. Direct-pathway medium spiny neurons (dMSNs) in the striatal patch compartment contain μ-opioid receptors (MORs). It remains unclear how chronic opioid exposure and withdrawal impact these MOR-expressing dMSNs and their outputs. Here, we report that MOR activation acutely suppressed GABAergic striatopallidal transmission in habenula-projecting globus pallidus neurons. Notably, withdrawal from repeated morphine or fentanyl administration potentiated this GABAergic transmission. Furthermore, intravenous fentanyl self-administration enhanced GABAergic striatonigral transmission and reduced midbrain dopaminergic activity. Fentanyl-activated striatal neurons mediated contextual memory retrieval required for conditioned place preference tests. Importantly, chemogenetic inhibition of striatal MOR+ neurons rescued fentanyl withdrawal-induced physical symptoms and anxiety-like behaviors. These data suggest that chronic opioid use triggers GABAergic striatopallidal and striatonigral plasticity to induce a hypodopaminergic state, which may promote negative emotions and relapse.

BACKGROUND: The low motor activity of the population in total is actually a serious medical and social problem, which correlates with the improvement of simplified living conditions and the emergence of innovative technologies. Therefore, the purpose of this work was proving the fact, that physical activity is useful not only for healthy people, but also therapeutic for individuals with chronic diseases. METHODS: Primary data, systematic reviews and meta-analyses describing the use of physical and massage therapy in the context of prevention and treatment were processed via the methods of comparative and analytical search. RESULTS: The biochemical mechanisms of alleviating the symptoms of chronic diseases, provided the patients have an active lifestyle, have been revealed; statistical information on the influence of physical activity on the change of quantitative physiological parameters and increase in survival rate has been provided, the protocols of massage therapy for pathologies of the respiratory organs and the musculoskeletal system have been considered; caveats and contraindications for training for specific cases have been identified. CONCLUSIONS: The positive value of sports training in the perspective of treating chronic diseases has been proven, and warnings and recommendations for patients regarding the organization of an active lifestyle in case of systemic pathologies and local functional disorders have been provided in the context of the conducted research. (Cite this article as: Wang W, Kozlova E, Chen L. The importance of medical and sports preventive and therapeutic measures for chronic diseases. Med Sport 2023;76:126-35. DOI: 10.23736/S0025-7826.23.04229-1)

Climate change and intensifying human activity are posing serious threats to marine organisms. The fluctuating inter-tidal zone forms a miniature ecosystem of a rapidly changing environment for studying biological adaptation. Transgenerational plasticity (TGP), an evolutionary phenomenon in which parental experience influences offspring phenotypes, provides an avenue for adaptation, but the molecular mechanism was poorly understood in marine mol-luscs. In this study, wild Pacific oysters (Crassostrea gigas), which were collected from intertidal zones, were used to conduct two-generation breeding in a subtidal area combined with a heat shock experiment in the laboratory to inves-tigate the intertidal environment-induced TGP under temperate subtidal condition and thermally exposed condition, respectively. We showed that TGP could influence the physiological phenotypes related to the status of oxidation and energy in non-stress-exposed subtidal offspring for at least two generations. Genomic DNA methylation exhibited heritable divergence between intertidal and subtidal oysters, and 1655 (or 42.83 %) differentially methylated genes (DMGs) in F0 were continuously reserved to F2, which may mediate physiological TGP by participating in biological processes including macromolecule metabolism, cellular responses to stress, and the positive regulation of molecular function, especially fatty acid metabolism. The intertidal experience also influenced the thermal plasticity of physio-logical phenotypes within and across generations. Totally, 320 (or 14.74 %) specific thermal response DMGs in the in-tertidal F0 generation were identified in F1 and F2, participating in pathways including carbohydrate, lipid, and energy metabolism, signal transduction, and the organismal immune system, which suggested transgenerational intertidal ef-fect mediated by these genes could positively contribute to stress adaptation and had potential applications for aqua -culture. This study demonstrates an epigenetic mechanism for TGP in stress adaptation in marine molluscs, and provides new avenues to improve the stress adaptation for marine resource conservation and aquaculture.

Background Increased levels of low-density lipoprotein cholesterol (LDL-C) have been identified as one potential risk factor for diabetic peripheral neuropathy (DPN) in patients. The current study seeks to clarify the link between LDL-C, hyperglycemia, and DPN in patients with type 2 diabetes mellitus (T2DM). Methods Here, a total of 120 T2DM individuals were recruited. These volunteers with T2DM were divided into 2 groups, based on the presence or absence of peripheral neuropathy. Additionally, their baseline characteristics were compared. Association among LDL-C and glycosylated hemoglobin (HbA1c) levels and DPN, particularly with respect to specific nerve conduction velocity were analyzed. To identify factors influencing DPN, regression was performed. Furthermore, mediation analysis was employed to evaluate the indirect, direct and total effects of LDL-C on specific nerve conduction velocity, with HbA1c serving as a mediator. Results Compared to 55 patients without DPN, 65 patients with DPN demonstrated elevated levels of LDL-C and HbA1c. Both LDL-C and HbA1c have been found to be associated with reduced the motor fiber conduction velocities of Ulnar (or the Common peroneal) nerve in diabetic patients. HbA1c is one of the known risk factors for DPN in individuals with T2DM. Further mediation analysis revealed that the effect of LDL-C on the Ulnar (or the Common peroneal) nerve motor fiber conduction velocities are fully mediated by HbA1c in patients with T2DM. Conclusions The impact of elevated LDL-C levels upon the Ulnar (or the Common peroneal) nerve motor fiber conduction velocities in patients with T2DM was found to be entirely mediated by increased HbA1c levels.