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1.
Purinergic Signal ; 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35478452

RESUMO

Upregulation of P2X3 receptor (P2X3R) has been strongly implicated in nociceptive signaling including bone cancer pain (BCP). The present study, using rat bone cancer model, aimed to explore the role of P2X3R in regulating rat pain behavior under the intervention of electroacupuncture (EA). The BCP model was successfully established by injection with MRMT-1 breast cancer cell into the medullary cavity of left tibia for 3 × 104 cells/3 µL PBS in rats as revealed by obvious bone destruction, decreased paw withdrawal thresholds (PWTs), and reduced paw withdrawal latencies (PWLs). Western blot analyses showed that P2X3R expression was significantly upregulated in ipsilateral lumbar 4-6 (L4-6) dorsal root ganglia (DRG), but the difference not seen in spinal cord dorsal horn (SCDH). With the in-depth study of P2X3R activation, we observed that intrathecal injection of P2X3R agonist α,ß-meATP aggravated MRMT-1 induced BCP, while injection of P2X3R inhibitor A-317491 alleviated pain. Subsequently, we demonstrated that BCP induced mechanical allodynia and thermal hyperalgesia were attenuated after EA treatment. Under EA treatment, total P2X3R protein expression in ipsilateral DRGs was decreased, and it is worth mentioning that decreased expression of P2X3R membrane protein, which indicated that both the expression and membrane trafficking of P2X3R were inhibited by EA. The immunofluorescence assay showed that EA stimulation exerted functions by reducing the expression of P2X3R-positive cells in ipsilateral DRGs of BCP rats. Ca2+ imaging analysis revealed that the EA stimulation decreased the percentage of α,ß-meATP responsive neurons in DRGs and inhibited calcium influx. Notably, the inhibitory effect of EA on mechanical allodynia and nociceptive flinches was abolished by intrathecal injection of α,ß-meATP. These findings demonstrated EA stimulation ameliorated mechanical allodynia and thermal hyperalgesia in rat model of MRMT-1-induced BCP. EA exerts analgesic effect on BCP by reducing the overexpression and functional activity of P2X3R in ipsilateral DRGs of BCP rats. Our work first demonstrates the critical and overall role of P2X3R in EA's analgesia against peripheral sensitization of MRMT-1-induced BCP and further supports EA as a potential therapeutic option for cancer pain in clinic.

2.
BMJ Open ; 12(3): e056632, 2022 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-35301212

RESUMO

INTRODUCTION: Postherpetic neuralgia (PHN) is the most common sequela of herpes zoster, and it is often refractory to guideline-recommended treatments. Acupuncture therapy, a wildly applied complementary-alternative treatment, may help in the management of PHN. Diverse types of acupuncture therapy for PHN have been proposed, however, their comparative efficacies remain unclear. This study protocol plans to compare the efficacy and safety of different acupuncture therapies for PHN. METHODS AND ANALYSIS: Databases including MEDLINE, Embase, Cochrane Library, Web of Science, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database, Wanfang Database, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, Chinese Clinical Trial Register and OpenGrey will be searched from their inception to January 2022. Randomised controlled trials (RCTs) assessing the effectiveness of acupuncture therapy on the management of PHN will be selected. The primary outcome is pain intensity. Secondary outcomes include negative emotions, sleep condition, quality of life and adverse events. Reviewers will conduct study selection, data extraction and risk of bias assessment procedures. Then, standard pair-wised meta-analysis and Bayesian network meta-analysis will be performed (if applicable). The Confidence in Network Meta-Analysis application will be used to assess the confidence in the evidence for the primary outcome. ETHICS AND DISSEMINATION: All data used for this study will be extracted from published RCTs, thus, no ethical approval will be required. The results of this systematic review will be disseminated through peer-reviewed journal and conference presentation. PROSPERO REGISTRATION NUMBER: CRD42020219576.


Assuntos
Terapia por Acupuntura , Herpes Zoster , Neuralgia Pós-Herpética , Terapia por Acupuntura/métodos , Herpes Zoster/etiologia , Humanos , Metanálise como Assunto , Metanálise em Rede , Neuralgia Pós-Herpética/terapia , Medição da Dor , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
3.
Purinergic Signal ; 2022 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-35218450

RESUMO

Diabetic neuropathic pain (DNP) is highly common in diabetes patients. P2X receptors play critical roles in pain sensitization. We previously showed that elevated P2X3 expression in dorsal root ganglion (DRG) contributes to DNP. However, the role of other P2X receptors in DNP is unclear. Here, we established the DNP model using a single high-dose streptozotocin (STZ) injection and investigated the expression of P2X genes in the DRG. Our data revealed elevated P2X2, P2X4, and P2X7 mRNA levels in DRG of DNP rats. The protein levels of P2X4 and P2X7 in DNP rats increased, but the P2X2 did not change significantly. To study the role of P2X4 and P2X7 in diabetes-induced hyperalgesia, we treated the DNP rats with TNP-ATP (2',3'-O-(2,4,6-trinitrophenyl)-adenosine 5'-triphosphate), a nonspecific P2X1-7 antagonist, and found that TNP-ATP alleviated thermal hyperalgesia in DNP rats. 2 Hz electroacupuncture is analgesic against DNP and could downregulate P2X4 and P2X7 expression in DRG. Our findings indicate that P2X4 and P2X7 in L4-L6 DRGs contribute to diabetes-induced hyperalgesia, and that EA reduces thermal hyperalgesia and the expression of P2X4 and P2X7.

4.
Zhongguo Zhen Jiu ; 42(2): 173-8, 2022 Feb 12.
Artigo em Chinês | MEDLINE | ID: mdl-35152582

RESUMO

OBJECTIVE: To observe the occurrence time of neuralgia and the expression of purinergic ligand-gated ion channel 7 receptor (P2X7R) in the dorsal horn of the spinal cord after intraperitoneal injection of streptozotocin (STZ) in diabetic rats, and to explore the effect of electroacupuncture (EA) and pretreatment of EA on the heat pain threshold and expression of P2X7R in the spinal dorsal horn in rats with diabetic neuropathic pain (DNP), and to explore the possible mechanism of EA for DNP. METHODS: PartⅠ: Thirty male SD rats were randomly selected from 64 male SD rats as the control group; the remaining rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model, and 30 rats were successfully modeled as the model group. The control group and the model group were divided into three subgroups respectively at 7, 14 and 21 days, with 10 rats in each subgroup. Body mass, fasting blood glucose (FBG) and thermal pain threshold were recorded at 7, 14 and 21 days after injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot. PartⅡ: Eight SD rats were randomly selected from 35 male SD rats as the blank group, and the remaining 27 rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model. The 24 rats with successful diabetes model were randomly divided into a DNP group, an EA group and a pre-EA group, 8 rats in each group. Fifteen to 21 days after STZ injection, the EA group received EA at "Zusanli" (ST 36) and "Kunlun" (BL 60), continuous wave, frequency of 2 Hz, 30 min each time, once a day; the intervention method in the pre-EA group was the same as that in the EA group. The intervention time was 8 to 14 days after STZ injection. The body mass, FBG and thermal pain threshold were recorded before STZ injection and 7, 14 and 21 days after STZ injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot 21 days after injection. RESULTS: PartⅠ: Compared with the control group, in the model group, the body mass was decreased and FBG was increased 7, 14 and 21 days after STZ injection (P<0.01), and the thermal pain threshold was decreased 14 and 21 days after STZ injection (P<0.05), and the expression of P2X7R in spinal dorsal horn was increased 7, 14 and 21 days after STZ injection (P<0.05, P<0.01). PartⅡ: Compared with the blank group, in the DNP group, the body mass was decreased and fasting blood glucose were increased 7, 14 and 21 days after STZ injection (P<0.01). Compared with the DNP group, in the pre-EA group, the heat pain threshold was increased 14 and 21 days after STZ injection (P<0.05), while in the EA group, the heat pain threshold was increased 21 days after STZ injection (P<0.01), and the expression of P2X7R in the dorsal horn in the EA group and the pre-EA group was decreased (P<0.01). CONCLUSION: The diabetic neuropathic pain is observed 14 days after STZ injection. EA could not only treat but also prevent the occurrence of DNP, and its mechanism may be related to down-regulation of P2X7R expression in the dorsal horn of the spinal cord.


Assuntos
Diabetes Mellitus Experimental , Eletroacupuntura , Neuralgia , Animais , Diabetes Mellitus Experimental/terapia , Masculino , Neuralgia/etiologia , Neuralgia/terapia , Ratos , Ratos Sprague-Dawley , Medula Espinal , Corno Dorsal da Medula Espinal
5.
Purinergic Signal ; 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34973115

RESUMO

Diabetic neuropathic pain (DNP) is frequent among patients with diabetes. We previously showed that P2X3 upregulation in dorsal root ganglia (DRG) plays a role in streptozotocin (STZ)-induced DNP but the underlying mechanism is unclear. Here, a rat model of DNP was established by a single injection of STZ (65 mg/kg). Fasting blood glucose was significantly elevated from the 1st to 3rd week. Paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) in diabetic rats significantly reduced from the 2nd to 3rd week. Western blot analysis revealed that elevated p-CaMKIIα levels in the DRG of DNP rats were accompanied by pain-associated behaviors while CaMKIIα levels were unchanged. Immunofluorescence revealed significant increase in the proportion of p-CaMKIIα immune positive DRG neurons (stained with NeuN) in the 2nd and 3rd week and p-CaMKIIα was co-expressed with P2X3 in DNP rats. KN93, a CaMKII antagonist, significantly reduce mechanical hyperalgesia and thermal hyperalgesia and these effects varied dose-dependently, and suppressed p-CaMKIIα and P2X3 upregulation in the DRGs of DNP rats. These results revealed that the p-CaMKIIα upregulation in DRG is involved in DNP, which possibly mediated P2X3 upregulation, indicating CaMKIIα may be an effective pharmacological target for DNP management.

6.
Structure ; 30(2): 240-251.e4, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-34727518

RESUMO

Despite previous structural analyses of bacteriophages, quite little is known about the structures and assembly patterns of cyanophages. Using cryo-EM combined with crystallography, we solve the near-atomic-resolution structure of a freshwater short-tailed cyanophage, Pam1, which comprises a 400-Å-long tail and an icosahedral capsid of 650 Å in diameter. The outer capsid surface is reinforced by trimeric cement proteins with a ß-sandwich fold, which structurally resemble the distal motif of Pam1's tailspike, suggesting its potential role in host recognition. At the portal vertex, the dodecameric portal and connected adaptor, followed by a hexameric needle head, form a DNA ejection channel, which is sealed by a trimeric needle. Moreover, we identify a right-handed rifling pattern that might help DNA to revolve along the wall of the ejection channel. Our study reveals the precise assembly pattern of a cyanophage and lays the foundation to support its practical biotechnological and environmental applications.


Assuntos
Bacteriófagos/química , Capsídeo/química , Cianobactérias/virologia , Sequenciamento Completo do Genoma/métodos , Microscopia Crioeletrônica , Cristalografia por Raios X , Tamanho do Genoma , Genoma Viral , Modelos Moleculares , Conformação Molecular , Montagem de Vírus
7.
BMJ Open ; 11(12): e052528, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34862291

RESUMO

INTRODUCTION: To date, there has been a lack of knowledge about the status, reporting completeness and methodological quality of pilot trials in the acupuncture field. Thus, this systematic review protocol aims to: (1) investigate publication trends and aspects of feasibility evaluated in acupuncture pilot trials; (2) identify the proportion of acupuncture pilot trials that lead to definitive trials and (3) assess the reporting completeness and methodological quality of pilot trials in acupuncture. METHODS AND ANALYSIS: Studies of acupuncture pilot randomised controlled trials published from 2011 to 2021 will be retrieved in seven databases in January 2022, including PubMed, Web of Science, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Database and Chinese Biomedical Literature Database. The methodological quality and reporting completeness of all included studies will be assessed using the risk of bias 2.0 tool (RoB 2) and the Consolidated Standards of Reporting Trials (CONSORT) extension to randomised pilot and feasibility trials, respectively. For the primary analysis, publication trends, aspects of feasibility and the proportion of pilot trials that lead to definitive trials will be analysed. A quantitative analysis of the methodological quality and reporting completeness of the included trials will be implemented by calculating the percentage of items reported in each domain of RoB 2 and CONSORT. The secondary analysis will adopt a regression analysis to identify factors associated with the reporting completeness. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. This study is planned to be submitted to a peer-reviewed academic journal.


Assuntos
Terapia por Acupuntura , Viés , Humanos , Projetos Piloto , Ensaios Clínicos Controlados Aleatórios como Assunto , Padrões de Referência , Revisões Sistemáticas como Assunto
8.
Medicine (Baltimore) ; 100(50): e28294, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34918706

RESUMO

BACKGROUND: Carpal tunnel syndrome (CTS) is the most common peripheral nerve compression syndrome of the upper limb. Plenty of studies showed the effects of acupuncture therapy on relieving pain and improving functional status for CTS patients. Diverse types of acupuncture therapies have been used in the treatment for CTS, but their relative treatment effects are poorly understood. This study will evaluate the effects of different acupuncture and related therapies for CTS by conducting a systematic review and Bayesian network meta-analysis (NMA). METHODS: We will search randomized controlled trials (RCTs) of acupuncture and related therapies for CTS in MEDLINE (via PubMed), EMBASE, Web of Science, Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database, Wanfang Database, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, Chinese Clinical Trial Register, and OpenGrey from inception to November 2021. Then, we will select eligible studies, extract data, and conduct risk of bias assessment using the Cochrane tool. Pairwise meta-analysis and Bayesian NMA will be performed in Stata 15.1 software and Aggregate Data Drug Information System 1.16.8 software. We will assess the quality of the evidence using the Confidence in Network Meta-Analysis application. RESULTS: In this study, the treatment effects and safety of different acupuncture and related therapies for CTS will be evaluated. CONCLUSION: This study will provide evidence for choosing the optimal acupuncture and related therapies in the treatment for CTS.


Assuntos
Terapia por Acupuntura , Síndrome do Túnel Carpal/terapia , China , Humanos , Metanálise em Rede , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
10.
J Virol ; 95(24): e0135621, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34549983

RESUMO

A-1(L) is a freshwater cyanophage with a contractile tail that specifically infects Anabaena sp. PCC 7120, one of the model strains for molecular studies of cyanobacteria. Although isolated for half a century, its structure remains unknown, which limits our understanding on the interplay between A-1(L) and its host. Here we report the 3.35 Å cryo-EM structure of A-1(L) capsid, representing the first near-atomic resolution structure of a phage capsid with a T number of 9. The major capsid gp4 proteins assemble into 91 capsomers, including 80 hexons: 20 at the center of the facet and 60 at the facet edge, in addition to 11 identical pentons. These capsomers further assemble into the icosahedral capsid, via gradually increasing curvatures. Different from the previously reported capsids of known-structure, A-1(L) adopts a noncovalent chainmail structure of capsid stabilized by two kinds of mortise-and-tenon inter-capsomer interactions: a three-layered interface at the pseudo 3-fold axis combined with the complementarity in shape and electrostatic potential around the 2-fold axis. This unique capsomer construction enables A-1(L) to possess a rigid capsid, which is solely composed of the major capsid proteins with an HK97 fold. IMPORTANCE Cyanobacteria are the most abundant photosynthetic bacteria, contributing significantly to the biomass production, O2 generation, and CO2 consumption on our planet. Their community structure and homeostasis in natural aquatic ecosystems are largely regulated by the corresponding cyanophages. In this study, we solved the structure of cyanophage A-1(L) capsid at near-atomic resolution and revealed a unique capsid construction. This capsid structure provides the molecular details for better understanding the assembly of A-1(L), and a structural platform for future investigation and application of A-1(L) in combination with its host Anabaena sp. PCC 7120. As the first isolated freshwater cyanophage that infects the genetically tractable model cyanobacterium, A-1(L) should become an ideal template for the genetic engineering and synthetic biology studies.


Assuntos
Anabaena/virologia , Bacteriófagos/química , Capsídeo/química , Microscopia Crioeletrônica/métodos , Bacteriófagos/classificação , Capsídeo/metabolismo , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Água Doce/microbiologia , Modelos Moleculares , Filogenia
11.
J Biol Chem ; 297(5): 101234, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34562453

RESUMO

Juvenile hormone (JH) acid methyltransferase (JHAMT) is a rate-limiting enzyme that converts JH acids or inactive precursors of JHs to active JHs at the final step of JH biosynthesis in insects and thus presents an excellent target for the development of insect growth regulators or insecticides. However, the three-dimensional properties and catalytic mechanism of this enzyme are not known. Herein, we report the crystal structure of the JHAMT apoenzyme, the three-dimensional holoprotein in binary complex with its cofactor S-adenosyl-l-homocysteine, and the ternary complex with S-adenosyl-l-homocysteine and its substrate methyl farnesoate. These structures reveal the ultrafine definition of the binding patterns for JHAMT with its substrate/cofactor. Comparative structural analyses led to novel findings concerning the structural specificity of the progressive conformational changes required for binding interactions that are induced in the presence of cofactor and substrate. Importantly, structural and biochemical analyses enabled identification of one strictly conserved catalytic Gln/His pair within JHAMTs required for catalysis and further provide a molecular basis for substrate recognition and the catalytic mechanism of JHAMTs. These findings lay the foundation for the mechanistic understanding of JH biosynthesis by JHAMTs and provide a rational framework for the discovery and development of specific JHAMT inhibitors as insect growth regulators or insecticides.


Assuntos
Bombyx/enzimologia , Proteínas de Insetos/química , Hormônios Juvenis/química , Metiltransferases/química , Animais , Bombyx/genética , Cristalografia por Raios X , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Hormônios Juvenis/biossíntese , Hormônios Juvenis/genética , Metiltransferases/genética , Metiltransferases/metabolismo , Domínios Proteicos
12.
Complement Ther Clin Pract ; 45: 101484, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34517216

RESUMO

BACKGROUND AND OBJECTIVE: Despite that acupuncture is effective in treating anxiety, depression and chronic stable angina pectoris (CSAP), it remains unclear whether acupuncture can treat CSAP, anxiety and depression simultaneously. This systematic review and meta-analysis aimed to investigate the efficacy of acupuncture on CSAP-associated anxiety and depression. METHODS: Eight electronic databases were searched to identify eligible randomized controlled trials (RCTs) or controlled clinical trials (i.e. "acupuncture alone or combined with standard care" versus " sham acupuncture alone, sham acupuncture with standard care, or standard care alone") from their inception to January 2021, which included PubMed, Embase, Web of Science, the Cochrane Library, CBM, CNKI, VIP and Wanfang Database. Data were extracted and meta analyses were performed using the RevMan 5.3. Risk of bias (ROB) 2.0 was used for methodological quality assessment. GRADEprofiler 3.2.2 was used to rate the quality of evidence. RESULTS: Seven trials involving 893 subjects were included. Meta-analysis results showed that acupuncture combined with standard care was more effective in relieving anxiety and depression, reducing angina attack frequency, and angina pain intensity than sham acupuncture with standard care and standard care alone. In addition, the effect remained until 16 weeks after acupuncture. The safety of acupuncture for CSAP-associated anxiety and depression was also high. Nonetheless, the quality of evidence ranged from low to moderate. CONCLUSION: Acupuncture may be used as an adjunctive therapy to treat CSAP-associated anxiety and depression. However, more high-quality RCTs are required to confirm our findings.


Assuntos
Terapia por Acupuntura , Angina Estável , Angina Estável/terapia , Ansiedade/etiologia , Ansiedade/terapia , Transtornos de Ansiedade , Depressão/terapia , Humanos
14.
Front Neurosci ; 15: 685715, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354561

RESUMO

Many cases of acute pain can be resolved with few side effects. However, some cases of acute pain may persist beyond the time required for tissue injury recovery and transit to chronic pain, which is hard to treat. The mechanisms underlying pain transition are not entirely understood, and treatment strategies are lacking. In this study, the hyperalgesic priming model was established on rats to study pain transition by injection of carrageenan (Car) and prostaglandin E2 (PGE2). The expression levels of protein kinase C epsilon (PKCε) and transient receptor potential vanilloid 1 (TRPV1) in the L4-L6 dorsal root ganglion (DRG) were investigated. Electroacupuncture (EA) is a form of acupuncture in which a small electric current is passed between a pair of acupuncture needles. EA was administrated, and its effect on hyperalgesia and PKCε and TRPV1 expression was investigated. The PKCε-TRPV1 signaling pathway in DRG was implicated in the pain transition. EA increased the pain threshold of model animals and regulated the high expression of PKCε and TRPV1. Moreover, EA also regulated hyperalgesia and high TRPV1 expression induced by selective PKCε activation. We also found that EA partly increased chronic pain threshold, even though it was only administered between the Car and PGE2 injections. These findings suggested that EA could prevent the transition from acute to chronic pain by inhibiting the PKCε and TRPV1 expression in the peripheral nervous system.

15.
J Cell Mol Med ; 25(15): 7485-7499, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34263977

RESUMO

Pulmonary arterial hypertension (PAH) is a form of obstructive vascular disease. Chronic hypoxic exposure leads to excessive proliferation of pulmonary arterial smooth muscle cells and pulmonary arterial endothelial cells. This condition can potentially be aggravated by [Ca2+ ] i mobilization. In the present study, hypoxia exposure of rat's model was established. Two-pore segment channels (TPCs) silencing was achieved in rats' models by injecting Lsh-TPC1 or Lsh-TPC2. The effects of TPC1/2 silencing on PAH were evaluated by H&E staining detecting pulmonary artery wall thickness and ELISA assay kit detecting NAADP concentrations in lung tissues. TPC1/2 silencing was achieved in PASMCs and PAECs, and cell proliferation was detected by MTT and BrdU incorporation assays. As the results shown, NAADP-activated [Ca2+ ]i shows to be mediated via two-pore segment channels (TPCs) in PASMCs, with TPC1 being the dominant subtype. NAADP generation and TPC1/2 mRNA and protein levels were elevated in the hypoxia-induced rat PAH model; NAADP was positively correlated with TPC1 and TPC2 expression, respectively. In vivo, Lsh-TPC1 or Lsh-TPC2 infection significantly improved the mean pulmonary artery pressure and PAH morphology. In vitro, TPC1 silencing inhibited NAADP-AM-induced PASMC proliferation and [Ca2+ ]i in PASMCs, whereas TPC2 silencing had minor effects during this process; TPC2 silencing attenuated NAADP-AM- induced [Ca2+ ]i and ECM in endothelial cells, whereas TPC1 silencing barely ensued any physiological changes. In conclusion, TPC1/2 might provide a unifying mechanism within pulmonary arterial hypertension, which can potentially be regarded as a therapeutic target.


Assuntos
Canais de Cálcio/metabolismo , Cálcio/metabolismo , Hipertensão Pulmonar/metabolismo , Hipóxia/metabolismo , NADP/análogos & derivados , Animais , Canais de Cálcio/genética , Células Cultivadas , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Hipertensão Pulmonar/etiologia , Hipóxia/complicações , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , NADP/metabolismo , Ratos , Ratos Wistar
16.
Microcirculation ; 28(6): e12715, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34008915

RESUMO

OBJECTIVES: Although both calcium-sensing receptor (CaSR) and canonical transient receptor potential (TRPC) proteins contribute to chronic hypoxia (CH)-induced pulmonary arterial smooth muscle cells (PASMCs) proliferation, the relationship between CaSR and TRPC in hypoxic PASMCs proliferation remains poorly understood. The goal of this study was to identify that CH promotes PASMCs proliferation through CaSR-TRPC pathway. METHODS: Rat PASMCs were isolated and treated with CH. Cell proliferation was assessed by cell counting, CCK-8 assay, and EdU incorporation. CaSR and TRPC expressions were determined by qPCR and Western blotting. Store-operated Ca2+ entry (SOCE) was assessed by extracellular Ca2+ restoration. RESULTS: In PASMCs, CH enhanced the cell number, cell viability and DNA synthesis, which is accompanied by upregulated expression of CaSR, TRPC1 and TRPC6. Negative CaSR modulators (NPS2143, NPS2390) inhibited, whereas positive modulators (spermine, R568) enhanced, the CH-induced increases in cell number, cell viability and DNA synthesis in PASMCs. Knockdown of CaSR by siRNA inhibited the CH-induced upregulation of TRPC1 and TRPC6 and enhancement of SOCE and attenuated the CH-induced enhancements of cell number, cell viability and DNA synthesis in PASMCs. However, neither siTRPC1 nor siTRPC6 had an effect on the CH-induced CaSR upregulation, although both significantly attenuated the CH-induced enhancements of cell number, cell viability and DNA synthesis in PASMCs. CONCLUSION: These results demonstrate that upregulated CaSR-TRPC1/6 pathway mediating PASMCs proliferation is an important pathogenic mechanism under hypoxic conditions.


Assuntos
Hipóxia , Animais , Cálcio/metabolismo , Proliferação de Células , Células Cultivadas , DNA , Hipertensão Pulmonar , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/metabolismo , Ratos , Transdução de Sinais , Canais de Cátion TRPC/genética , Canal de Cátion TRPC6
17.
Artigo em Inglês | MEDLINE | ID: mdl-33868440

RESUMO

OBJECTIVE: By comparing the differences in microcirculatory responses of the heart and lung meridians induced by moxibustion on these two meridians, respectively, this study aimed to investigate the specificity for site-to-site association on body surface between different meridians. METHODS: Eighty healthy adults were enrolled and divided into the lung meridian intervention group and heart meridian intervention group in a ratio of 1 : 1. Three-channel laser Doppler flowmetry was used to monitor microcirculatory responses for the heart and lung meridians. Primary outcome was change of blood perfusion units (PU) of three measurement sites along the two meridians. RESULTS: In the lung meridian intervention group, following moxibustion performed at LU5 of the lung meridian, PU in the distal site of the lung meridian increased significantly. By contrast, the PU of HT3 in the heart meridian, which was nearest to the moxibustion site, did not change significantly. PU in the distal site of the heart meridian declined. Meanwhile, significant difference in PU change was detected between the distal site of the lung meridian and the other two control sites of the heart meridians during moxibustion and postmoxibustion. Alternatively, similar to the results of the lung meridian intervention group, the specificity of microcirculatory response between the heart and lung meridians was observed in the heart meridian intervention group. CONCLUSIONS: For the heart and lung meridians, the effect of moxibustion-induced microcirculatory response may be more related to meridian routes than the specific distance between two sites located at different meridians, thereby supporting possible specificity for site-to-site association on the body surface between these two meridians. Nevertheless, given that only two meridians and limited measurement sites were compared, all current findings are not sufficiently robust. Further research should be conducted to investigate more meridians and measurement sites.

18.
Cytotechnology ; 73(2): 189-201, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33927476

RESUMO

Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling, which exists in both pulmonary arteries and pulmonary veins. Pulmonary vascular remodeling stems from excessive proliferation of pulmonary vascular myocytes. Platelet-derived growth factor-BB (PDGF-BB) is a vital vascular regulator whose level increases in PH human lungs. Although the mechanisms by which pulmonary arterial smooth muscle cells respond to PDGF-BB have been studied extensively, the effects of PDGF-BB on pulmonary venous smooth muscle cells (PVSMCs) remain unknown. We herein examined the involvement of calcium sensing receptor (CaSR) in PDGF-BB-induced PVSMCs proliferation under hypoxic conditions. In PVSMCs isolated from rat intrapulmonary veins, PDGF-BB increased the cell number and DNA synthesis under normoxic and hypoxic conditions, which was accompanied by upregulated CaSR expression. The influences of PDGF-BB on proliferation and CaSR expression in hypoxic PVSMCs were greater than that in normoxic PVSMCs. In hypoxic PVSMCs superfused with Ca2+-free solution, restoration of extracellular Ca2+ induced an increase of [Ca2+]i, which was significantly smaller than that in PDGF-BB-treated hypoxic PVSMCs. The positive CaSR modulator spermine enhanced, whereas the negative CaSR modulator NPS2143 attenuated, the extracellular Ca2+-induced [Ca2+]i increase in PDGF-BB-treated hypoxic PVSMCs. Furthermore, the spermine enhanced, whereas the NPS2143 inhibited, PDGF-BB-induced proliferation in hypoxic PVSMCs. Silencing CaSR with siRNA attenuated the extracellular Ca2+-induced [Ca2+]i increase in PDGF-BB-treated hypoxic PVSMCs and inhibited PDGF-BB-induced proliferation in hypoxic PVSMCs. In conclusion, these results demonstrated that CaSR mediating PDGF-BB-induced excessive PVSMCs proliferation is an important mechanism involved in the initiation and progression of PVSMCs proliferation under hypoxic conditions.

19.
Protein Sci ; 30(8): 1566-1576, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33928692

RESUMO

Carboxysome is an icosahedral self-assembled microcompartment that sequesters RuBisCO and carbonic anhydrases within a selectively permeable protein shell. The scaffolding proteins, CcmM, and CcmN were proposed to act as adaptors that crosslink the enzymatic core to shell facets. However, the details of interaction pattern remain unknown. Here we obtained a stable heterotrimeric complex of CcmM γ-carbonic anhydrase domain (termed CcmMNT ) and CcmN, with a 1:2 stoichiometry, which interacts with the shell proteins CcmO and CcmL in vitro. The 2.9 Å crystal structure of this heterotrimer revealed an asymmetric bundle composed of one CcmMNT and two CcmN subunits, all of which adopt a triangular left-handed ß-helical barrel structure. The central CcmN subunit packs against CcmMNT and another CcmN subunit via a wall-to-edge or wall-to-wall pattern, respectively. Together with previous findings, we propose CcmMNT -CcmN functions as an adaptor to facilitate the recruitment of shell proteins and the assembly of intact ß-carboxysome.


Assuntos
Proteínas de Bactérias , Complexos Multiproteicos , Organelas , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Dióxido de Carbono/metabolismo , Anidrases Carbônicas/química , Anidrases Carbônicas/metabolismo , Cristalização , Modelos Moleculares , Complexos Multiproteicos/química , Complexos Multiproteicos/metabolismo , Organelas/química , Organelas/metabolismo , Conformação Proteica , Ribulose-Bifosfato Carboxilase/química , Ribulose-Bifosfato Carboxilase/metabolismo , Synechococcus/química , Synechococcus/metabolismo
20.
Zhongguo Zhen Jiu ; 41(4): 451-7, 2021 Apr 12.
Artigo em Chinês | MEDLINE | ID: mdl-33909370

RESUMO

OBJECTIVE: To systematically evaluate the efficacy and safety of conventional therapy combined with moxibustion in the treatment of chronic obstructive pulmonary disease (COPD) in stable phase based on Meta-analysis medicine. METHODS: The randomized controlled trials (RCTs) of moxibustion as adjuvant therapy for COPD were retrieved from the databases of CNKI, Wanfang, SinoMed, PubMed, Web of Science, Cochrane Library and Ebsco. RevMan5.3 software was used for Meta analysis, and the quality of evidence was evaluated according to GRADE standards. RESULTS: A total of 16 RCTs were included, involving 1425 patients. The results of Meta-analysis showed that: compared with the conventional treatment, ①the adjuvant therapy with moxibustion had advantages in reducing the number of acute exacerbations [MD=-0.31, 95%CI:-0.49--0.13, P=0.0006]; ②the adjuvant therapy with moxibustion improved lung function significantly [FEV1% (MD=4.00, 95%CI:2.63-5.37, P<0.000 01) and FEV1/FVC (MD=3.56, 95%CI:1.69-5.43, P=0.000 2)]; ③the adjuvant therapy with moxibustion could extend the 6 min walking distance (6WMD) (MD=35.00, 95%CI:18.02-51.99, P<0.000 1); ④the adjuvant therapy with moxibustion could improve the modified British Medical Research Council breathing questionnaire (mMRC) classification significantly (MD=-0.62, 95%CI:-1.18--0.05, P=0.03); ⑤no adverse reaction was reported in the included literature. CONCLUSION: The efficacy of moxibustion as adjuvant therapy for COPD in stable phase is better than that of simple conventional therapy. Due to insufficient clinical evidence and the limitations of this study, clinical safety is unclear and further evidence is needed to support the results.


Assuntos
Moxibustão , Doença Pulmonar Obstrutiva Crônica , Humanos , Pulmão , Doença Pulmonar Obstrutiva Crônica/terapia , Resultado do Tratamento
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