Exploring the role of differentially expressed metabolic genes and their mechanisms in bone metastatic prostate cancer.

Background: Approximately 10-20% of patients diagnosed with prostate cancer (PCa) evolve into castration-resistant prostate cancer (CRPC), while nearly 90% of patients with metastatic CRPC (mCRPC) exhibit osseous metastases (BM). These BM are intimately correlated with the stability of the tumour microenvironment. Purpose: This study aspires to uncover the metabolism-related genes and the underlying mechanisms responsible for bone metastatic prostate cancer (BMPCa). Methods: Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets of PCa and BM were analyzed through R Studio software to identify differentially expressed genes (DEGs). The DEGs underwent functional enrichment via Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), with key factors screened by a random forest utilized to establish a prognostic model for PCa. The study explored the relationship between DEGs and the stability of the immune microenvironment. The action and specificity of CRISP3 in PCa was validated through western blot analysis, CCK-8 assay, scratch assay, and cellular assay. Results: The screening of GEO and TCGA datasets resulted in the identification of 199 co-differential genes. Three DEGs, including DES, HBB, and SLPI, were selected by random forest classification model and cox regression model. Immuno-infiltration analysis disclosed that a higher infiltration of naïve B cells and resting CD4 memory T cells occurred in the high-expression group of DES, whereas infiltration of resting M1 macrophages and NK cells was greater in the low-expression group of DES. A significant infiltration of neutrophils was observed in the high-expression group of HBB, while greater infiltration of gamma delta T cells and M1 macrophages was noted in the low-expression group of HBB. Resting dendritic cells, CD8 T cells, and resting T regulatory cells (Tregs) infiltrated significantly in the high-expression group of SLPI, while only resting mast cells infiltrated significantly in the low-expression group of SLPI. CRISP3 was established as a critical gene in BMPCa linked to DES expression. Targeting CRISP3, d-glucopyranose may impact tumour prognosis. During the mechanistic experiments, it was established that CRISP3 can advance the proliferation and metastatic potential of PCa by advancing epithelial-to-mesenchymal transition (EMT). Conclusion: By modulating lipid metabolism and maintaining immunological and microenvironmental balance, DES, HBB, and SLPI suppress prostate cancer cell growth. The presence of DES-associated CRISP3 is a harbinger of unfavorable outcomes in prostate cancer and may escalate tumor proliferation and metastatic capabilities by inducing epithelial-mesenchymal transition.

Linking Heat Shock Protein 70 and Parkin in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease that affects millions of elderly people worldwide and is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The precise mechanisms underlying the pathogenesis of PD are still not fully understood, but it is well accepted that the misfolding, aggregation, and abnormal degradation of proteins are the key causative factors of PD. Heat shock protein 70 (Hsp70) is a molecular chaperone that participates in the degradation of misfolded and aggregated proteins in living cells and organisms. Parkin, an E3 ubiquitin ligase, participates in the degradation of proteins via the proteasome pathway. Recent studies have indicated that both Hsp70 and Parkin play pivotal roles in PD pathogenesis. In this review, we focus on discussing how dysregulation of Hsp70 and Parkin leads to PD pathogenesis, the interaction between Hsp70 and Parkin in the context of PD and their therapeutic applications in PD.

[Effect of different suspension moxibustion methods on syndrome characteristics of rats with rheumatoid arthritis of heat bi syndrome based on "moxibustion can be used for heat syndrome"].

OBJECTIVE: To observe the effects of different suspension moxibustion methods on the syndrome characteristics and inflammatory factors of rats with rheumatoid arthritis (RA) of heat bi syndrome and to prove the concept of "moxibustion can be used for heat syndrome". METHODS: Among seventy Wistar rats, 12 rats were randomly selected as a normal group, and the remaining rats were induced by collagen combined with wind, dampness, and heat environmental stimulation to establish the RA model of heat bi syndrome. Forty-eight rats with successful model establishment were further randomly divided into a model group and three moxibustion groups (mild moxibustion group, rotating moxibustion group and sparrow-pecking moxibustion group), with 12 rats in each group. The acupoints "Quchi" (LI 11), "Dazhui" (GV 14) and ashi point were used in all moxibustion groups, with mild moxibustion, rotating moxibustion, and sparrow-pecking moxibustion intervention given respectively, each acupoint was treated with moxibustion for 10 min a day, and 6 days were considered one course of treatment, with a total of three courses. After the intervention, the arthritis index (AI), the Evans blue (EB) extravasated volume in the soft tissue of the right hind paw, and the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-10 in the serum were measured by ELISA in each group. The volume of the bilateral hind paw was measured; the infrared thermal imaging was collected to analyze the temperature of the plantar area of the bilateral foot pads, and the reaction time of plantar heat pain was calculated before and after modeling, as well as after the 1st, 2nd and 3rd courses of interrention. The ankle dorsiflexion angle of the right hind foot was also measured before and after modeling, as well as after the intervention. RESULTS: After modeling, compared with the normal group, the rats in the model group had more high-temperature areas in the bilateral hind limbs, abnormal AI score, abnormal bilateral hind paw volume, abnormal temperature of the plantar area of the bilateral foot pads, abnormal foot pain response time, abnormal right hind ankle dorsiflexion angle, abnormal right hind paw soft tissue EB extravasation, and abnormal serum TNF-α and IL-10 levels (P<0.01, P<0.05). After the intervention, compared with the model group, the rats in each moxibustion group had decreased or disappeared high-temperature areas in the bilateral hind limbs, EB extravasated volume in the soft tissue of the right hind paw was reduced (P<0.05), and the right ankle dorsiflexion angle was increased (P<0.05), serum level of TNF-α was reduced, and level of IL-10 increased (P<0.05); the AI scores in the mild moxibustion group and the sparrow-pecking moxibustion group was decreased (P<0.01, P<0.05). After the 1st, 2nd and 3rd courses of intervention, compared with the model group, the bilateral hind paw volume of rats in each moxibustion group was decreased (P<0.05, P<0.01), and plantar heat pain reaction time was increased (P<0.05). After the 2nd course and the 3rd course of intervention, the temperature of the right hind paw pad area was decreased in each moribustion group (P<0.05); after the 3rd courses of intervention, the temperature of the left hind paw pad area was decreased in the mild moxibustion group (P<0.05). CONCLUSION: Suspension moxibustion could adjust the serum levels of TNF-α and IL-10 to improve the syndrome characteristics of RA rats of heat bi syndrome, such as joint redness, swelling, heat, pain and activity restriction. The effect of mild moxibustion is the most prominent. The findings could provide scientific basis for "moxibustion can be used for heat syndrome".

Vitamin B12 Ameliorates the Pathological Phenotypes of Multiple Parkinson's Disease Models by Alleviating Oxidative Stress.

Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by progressive loss of dopaminergic neurons in the substantia nigra of the midbrain. The etiology of PD has yet to be elucidated, and the disease remains incurable. Increasing evidence suggests that oxidative stress is the key causative factor of PD. Due to their capacity to alleviate oxidative stress, antioxidants hold great potential for the treatment of PD. Vitamins are essential organic substances for maintaining the life of organisms. Vitamin deficiency is implicated in the pathogenesis of various diseases, such as PD. In the present study, we investigated whether administration of vitamin B12 (VB12) could ameliorate PD phenotypes in vitro and in vivo. Our results showed that VB12 significantly reduced the generation of reactive oxygen species (ROS) in the rotenone-induced SH-SY5Y cellular PD model. In a Parkin gene knockout C. elegans PD model, VB12 mitigated motor dysfunction. Moreover, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse PD model, VB12 also displayed protective effects, including the rescue of mitochondrial function, dopaminergic neuron loss, and movement disorder. In summary, our results suggest that vitamin supplementation may be a novel method for the intervention of PD, which is safer and more feasible than chemical drug treatment.

Dynamic Quantitative Trait Loci Mapping for Plant Height in Recombinant Inbred Line Population of Upland Cotton.

Plant height (PH) is a key plant architecture trait for improving the biological productivity of cotton. Ideal PH of cotton is conducive to lodging resistance and mechanized harvesting. To detect quantitative trait loci (QTL) and candidate genes of PH in cotton, a genetic map was constructed with a recombinant inbred line (RIL) population of upland cotton. PH phenotype data under nine environments and three best linear unbiased predictions (BLUPs) were used for QTL analyses. Based on restriction-site-associated DNA sequence (RAD-seq), the genetic map contained 5,850 single-nucleotide polymorphism (SNP) markers, covering 2,747.12 cM with an average genetic distance of 0.47 cM. Thirty-seven unconditional QTL explaining 1.03-12.50% of phenotypic variance, including four major QTL and seven stable QTL, were identified. Twenty-eight conditional QTL explaining 3.27-28.87% of phenotypic variance, including 1 major QTL, were identified. Importantly, five QTL, including 4 stable QTL, were both unconditional and conditional QTL. Among the 60 PH QTL (including 39 newly identified), none of them were involved in the whole period of PH growth, indicating that QTL related to cotton PH development have dynamic expression characteristics. Based on the functional annotation of Arabidopsis homologous genes and transcriptome data of upland cotton TM-1, 14 candidate genes were predicted within 10 QTL. Our research provides valuable information for understanding the genetic mechanism of PH development, which also increases the economic production of cotton.

ApoE deficiency promotes non-alcoholic fatty liver disease in mice via impeding AMPK/mTOR mediated autophagy.

AIM: This work was to investigate the relationship between ApoE and autophagy regulated by AMPK/mTOR pathway in the pathological process of NAFLD. MAIN METHODS: Both WT and ApoE-/- mice were divided into two groups and allocated into either a normal chow (ND) or a high-fat diet (HFD) for 8 weeks. After that, we detected the indicators of lipid accumulation, hepatic injury, mitochondrial function hallmark, autophagy, apoptosis, inflammation, and oxidative stress by commercially available kits, immunohistochemistry, immunofluorescent staining, and western blot. KEY FINDING: We found the lipid levels of serum and liver, and hepatic injury were significantly increased in the ApoE-/--HFD group compared to other groups. ApoE-/- mice exhibited increased deposition of fat in liver tissue. The PGC1α, NRF1, ATP, p-AMPK, AMPK, Beclin1, and LC3 levels were downregulated and ROS, p-mTOR, and mTOR were increased in the ApoE-/--HFD group compared to WT-HFD group. When treated with AMPK and autophagy activators, AICAR and rapamycin, these pathologies and protein levels can be rescued. The expression levels of apoptosis-related proteins, inflammation, and oxidative stress were increased in the ApoE-/--HFD group compared to the WT-HFD group. SIGNIFICANCE: Our results indicated that ApoE deficiency can regulate AMPK/mTOR pathway, which leads to NAFLD most likely by modulating hepatic mitochondrial function.

[Progress of the Mechanism of Acupuncture to Promote Repair of Facial Nerve Injury].

Facial nerve injury results in facial muscle movement disorders that interferes with patient's life. Acupuncture is an effective therapy for facial nerve injury, but its mechanism has not been clarified. The evidence supports that acupuncture can accelerate the repair of facial nerve injury by adjusting the electric wave of patient's facial muscle, improving facial blood circulation, and promoting the expression of cell and protein molecule.

[Acupuncture Intervention Improves Behavior Reactions and Learning-memory Ability in Post-traumatic Stress Disorder Rats].

OBJECTIVE: To observe the therapeutic effect of acupuncture in the treatment of post-traumatic stress disorder (PTSD)-induced abnormal behavior reactions and learning-memory ability in rats with traumatic injury. METHODS: Sixty male SD rats were randomly divided into control, model, model＋animal capturing (capturing), medication and acupuncture groups (n＝12 rats in each). The PTSD model was established by "electric shock plus incarceration" method. Acupuncture was applied to "Baihui" (GV 20), and unilateral "Neiguan" (PC 6), "Shenmen" (HT 7) and "Taichong" (LR 3) once daily for 12 days. The rats in the medication group were treated by gavage of Paroxetine Hydrochloride solution (0.42 mg/mL), once daily for 12 days. The open field test containing horizontal (crossing grid lines) and rearing tests was performed for examining the rats' locomotor activity and anxiety-like behavior; and location navigation (escape latency) and special probe tests (platform quadrant crossing times) of Morris water maze tasks were detected for assessing the rats' learning-memory ability. On day 12 of the experiments, the rats were submitted to 3 consecutive sessions of open field tests for observing the time of familiar objects (TF) and the time of novelty object (TN) of exploration in 5 min (an object-location and an object-recognition tasks), followed by calculating the discrimination index [DI＝(TN－TF)/(TN＋TF)x100%]. RESULTS: After modeling, compared with the control group, the numbers of crossed grids and rearing, and DI were significantly decreased (P<0.05), while the number of fecal pellets and escape latency were significantly increased in both the model and capturing groups (P<0.05). After the intervention, the number of both crossed grids and rearing, platform quadrant crossing times, and DI were considerably increased (P<0.05), and the rats' escape latency and fecal pellet number were obviously decreased in both medication and acupuncture groups relevant to the model and capturing groups (P<0.05). No significant differences were found between the acupuncture and medication groups in the above mentioned 5 indexes (P>0.05)．. CONCLUSION: Acupuncture can effectively reduce anxiety-like behavior and improve the impaired learning-memory ability in PTSD rats.

[Review on Modern Repair Mechanism of Moxibustion for Treating Inflammatory Damage of Rheumatoid Arthritis].

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Persistent inflammation of the synovial membrane is the main characteristic pathological symptom. Moxibustion for treating RA has achieved significant clinical effect in recent years. A large number of experimental studies have also shown that moxibustion promoted the repair of inflammatory damage induced by RA. Based on summarizing 10 years related literatures, the authors analyzed the repair mechanisms of moxibustion for inflammatory damage in RA from central mechanisms including glucocorticoid receptor, melatonine, hypothalamic-pituitary-adrenal axis, and cholinergic nerve to peripheral mechanisms including local inflammatory mediators, cytokine, and inflammatory cell signaling pathway, so as to provide evidences and reference for further research.

[Exploration of acupoints selection law for post-traumatic stress disorder treated with acupuncture and moxibustion].

To analyze the modern clinical literature on post-traumatic stress disorder(PTSD) treated with acupuncture and moxibustion so as to summarize the acupoints selection law. The related articles from 2005 to 2014 were collected and then the frequencies were statistically analyzed. Finally 16 papers were gathered,while the main acupoints among the 23 acupoints refer to Baihui(GV 20),Sishencong(EX-HN 1),Shenting(GV 24),Fengchi(GB 20),Shenmen(HT 7),Neiguan(PC 6),Taichong(LR 3) and Sanyinjiao(SP 6). It is concluded that the law means taking smoothing liver and governor vessel to regulate the spirit as priority,and assisted by nourishing kidney and supporting yang to peace the spirit,as well as strengthening spleen and helping qi to smooth meridians.

["Warming-promotion acupuncture" on knee osteoarthritis:a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy differences between warming-promotion acupuncture, mild reinforcing-reducing acupuncture and acupoint injection for knee osteoarthritis (KOA). METHODS: Ninety cases of KOA were randomly assigned into a warming-promotion acupuncture group (group A), a mild reinforcing-reducing acupuncture group (group B) and a sodium hyaluronate group (group C), 30 cases in each one. Patients in the group A and group B were treated at Xuehai (SP 10), Heding (EX-LE 2), Liangqiu (ST 34), Neixiyan (EX-LE 4), Dubi (ST 35), Xizhong (Extra), Yanglingquan (GB 34), Yinlingquan (SP 9), Zusanli (ST 36), and acupoints could be added or reduced based on syndrome differentiation; warming-promotion acupuncture was applied in the group A and mild reinforcing-reducing method was applied in the group B. Patients in the group C were treated with injection of sodium hyaluronate at any of Neixiyan (EX-LE 4), Dubi (ST 35) or Xizhong (Extra). Treatment was given once a day for group A and group B, and ten days were taken as one course; the injection was given every 5 days, and 2 times were taken as one course. There was an interval of 2 days between courses in the three groups. After three courses, the symptom and sign score and clinical efficacy were observed in the three groups. RESULTS: Compared with the group B and group C, the symptom and sign score was significantly reduced after treatment in the group A (all P<0.05). The total effective rate was 100.00% (30/30) in the group A, which was superior to 90.00% (27/30) in the group B (P<0.05) and 73.33% (22/30) in the group C (P<0.01). CONCLUSIONS: The clinical efficacy of warming-promotion acupuncture on KOA is obviously superior to the mild reinforcing-reducing acupuncture and injection of sodium hyaluronate, indicating its positive efficacy.

[Modern research progress regarding effect mechanism of acupuncture on post-traumatic stress disorder].

From the TCM theoretical basis and the evidences of acupoint selection and acupuncture and moxibustion methods regarding acupuncture for post-traumatic stress disorder (PTSD), a theoretical discussion is made in this article, also a review regarding the key mechanism of experiment researches on acupuncture for PTSD is made from aspects of neurobiology and brain functional imaging, etc., which could further clarify the effect mechanism of acupuncture on PTSD. It is found that PTSD is a kind of stress syndrome accompanied with a variety of abnormal mental symptom , and acupuncture has superior effect on PTSD. Based on these, the research progress and deficiency on current mechanism study of PTSD are reviewed, hoping to offer ideas for upcoming research and to serve the clinical practice better.