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1.
Front Pharmacol ; 13: 935714, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35899110

RESUMO

Metabolic hypertension (MH) is the most common type of hypertension worldwide because of unhealthy lifestyles, such as excessive alcohol intake and high-sugar/high-fat diets (ACHSFDs), adopted by humans. Poor diets lead to a decrease in the synthesis of short-chain fatty acids (SCFAs), which are produced by intestinal flora and transferred by G protein-coupled receptors (GPCRs), resulting in impaired gastrointestinal function, disrupted metabolic processes, increased blood pressure (BP), and ultimately, MH. It is not clear whether Dendrobium officinale polysaccharide (DOPS) can mediate its effects by triggering the SCFAs-GPCR43/41 pathway. In this study, DOPS, with a content of 54.45 ± 4.23% and composition of mannose, glucose, and galacturonic acid at mass percentages of 61.28, 31.87, and 2.53%, was isolated from Dendrobium officinale. It was observed that DOPS, given to rats by intragastric administration after dissolution, could lower the BP and improve the abnormal lipid metabolic processes in ACHSFD-induced MH rats. Moreover, DOPS was found to increase the production, transportation, and utilization of SCFAs, while improving the intestinal flora and strengthening the intestinal barrier, as well as increasing the intestinal levels of SCFAs and the expression of GPCR43/41. Furthermore, DOPS improved vascular endothelial function by increasing the expression of GPCR41 and endothelial nitric oxide synthase in the aorta and the nitric oxide level in the serum. However, these effects were all reversed by antibiotic use. These findings indicate that DOPS is the active component of Dendrobium officinale, and it can reverse MH in rats by activating the intestinal SCFAs-GPCR43/41 pathway.

2.
Comb Chem High Throughput Screen ; 25(8): 1294-1303, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34053424

RESUMO

AIMS AND OBJECTIVES: Fructose, as a ubiquitous monosaccharide, can promote ATP consumption and elevate circulating Uric Acid (UA) levels. Our previous studies have confirmed that the macroporous resin extract of Dendrobium officinale leaves (DoMRE) could reduce the UA level of rats with hyperuricemia induced by a high-purine diet. This study aimed to investigate whether DoMRE had a UA-lowering effect on rats with hyperuricemia caused by fructose combined with potassium oxonate, so as to further clarify the UA-lowering effect of DoMRE, and to explore the UAlowering effect of DoMRE on both UA production and excretion. MATERIALS AND METHODS: Rats with hyperuricemia induced by fructose and potassium oxonate were administered with DoMRE and vehicle control, respectively, to compare the effects of the drugs. At the end of the experiment, the Serum Uric Acid (SUA) and Creatinine (Cr) levels were measured using an automatic biochemical analyzer, the activities of xanthine oxidase (XOD) were measured using an assay kit, and the protein expressions of Urate Transporter 1 (URAT1), glucose transporter 9 (GLUT9), and ATP-Binding Cassette Superfamily G member 2 (ABCG2) were assessed using immune-histochemical and western blot analyses. Hematoxylin and eosin staining was used to assess the histological changes in the kidney, liver, and intestine. RESULTS: Fructose and potassium induced hyperuricemia in rats. Meanwhile, the activities of XOD were markedly augmented, the expression of URAT1 and GLUT9 was promoted, and the expression of ABCG2 was reduced, which were conducive to the elevation of UA. However, exposure to DoMRE reversed these fructose- and potassium oxonate-induced negative alternations in rats. The activities of XOD were recovered to the normal level, reducing UA formation; the expressions of URAT1, ABCG2, and GLUT9 returned to the normal level, resulting in an increase in renal urate excretion. CONCLUSION: DoMRE reduces UA levels in rats with hyperuricemia induced by fructose combined with potassium oxonate by inhibiting XOD activity and regulating the expression of ABCG2, URAT1, and GLUT9. DoMRE is a potential therapeutic agent for treating hyperuricemia through inhibiting UA formation and promoting UA excretion.


Assuntos
Dendrobium , Hiperuricemia , Trifosfato de Adenosina/metabolismo , Animais , Frutose , Hiperuricemia/induzido quimicamente , Hiperuricemia/tratamento farmacológico , Rim/metabolismo , Ácido Oxônico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta , Ratos , Ácido Úrico , Xantina Oxidase
3.
Artigo em Inglês | MEDLINE | ID: mdl-34122607

RESUMO

Dendrobium officinale (DOF) is a traditional Chinese edible and officinal plant. Ultrafine DOF powder (DOFP) can regulate lipids and histopathology in the liver, but the underlying mechanisms of hepatic fatty acid (FA) metabolism, which is generally correlated with the development of nonalcoholic fatty liver disease (NAFLD), remain unclear. The purpose of the present study was to investigate whether DOFP treatment alters hepatic FA metabolism in NAFLD mice by using multidimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) and analyse the underlying mechanisms. A 3-week DOFP treatment prevented lipid deposition and improved hepatic histopathology in NAFLD mice after withdrawal from the high-sucrose, high-fat (HSHF) diet, and it decreased triglyceride and FA content in the liver. Furthermore, the C16 : 0/C14 : 0 and C18 : 1/18 : 0 ratios in FAs were significantly decreased in the DOFP treatment group, and the C20 : 4/C20 : 3 and C22 : 4/C22 : 3 ratios were increased, and saturated FA was inhibited. Additionally, DOFP treatment significantly increased the content of two FA ß-oxidation-related proteins (carnitine palmitoyltransferase 1-α and acyl-coenzyme A oxidase 1). It also decreased the content of a FA synthesis-related protein (fatty acid synthase), a FA desaturation-related protein (stearoyl-coenzyme A desaturase-1), and a FA uptake-related protein (fatty acid transport protein 2). Moreover, DOFP treatment improved dysregulated levels of major phospholipids in the livers of model mice. The results of this study confirm that DOFP treatment in NAFLD mice has liver recovery effects by regulating FA metabolism.

4.
Ecotoxicol Environ Saf ; 219: 112336, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34044310

RESUMO

Heavy metals are widely distributed in the environment due to the natural processes and anthropogenic human activities. Their migration into no contaminated areas contributing towards pollution of the ecosystems e.g. soils, plants, water and air. It is recognized that heavy metals due to their toxicity, long persistence in nature can accumulate in the trophic chain and cause organism dysfunction. Although the popularity of herbal medicine is rapidly increasing all over the world heavy metal toxicity has a great impact and importance on herbal plants and consequently affects the quality of herbal raw materials, herbal extracts, the safety and marketability of drugs. Effective control of heavy metal content in herbal plants using in pharmaceutical and food industries has become indispensable. Therefore, this review describes various important factors such as ecological and environmental pollution, cultivation and harvest of herbal plants and manufacturing processes which effects on the quality of herbal plants and then on Chinese herbal medicines which influence human health. This review also proposes possible management strategies to recover environmental sustainability and medication safety. About 276 published studies (1988-2021) are reviewed in this paper.


Assuntos
Produtos Agrícolas/química , Metais Pesados/análise , Plantas Medicinais/química , Poluentes do Solo/análise , China , Medicamentos de Ervas Chinesas , Ecossistema , Monitoramento Ambiental , Poluição Ambiental , Humanos , Solo
5.
Food Funct ; 12(12): 5524-5538, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34002173

RESUMO

Given the increasing global trend toward unhealthy lifestyles and dietary decisions, such as "over-consumption of alcohol, and high sugar and fat diets" (ACHSFDs), it is not surprising that metabolic hypertension (MH) is now the most common type of hypertension. There is an urgent, global need for effective measures for the prevention and treatment of MH. Improper diet leads to decreased short-chain fatty acid (SCFA) production in the gut, leading to decreased gastrointestinal function, metabolism, and blood pressure as a result of signaling through G-protein-coupled receptors (GPCRs), ultimately causing MH. Previous studies have suggested that Dendrobium officinale (DO) may improve gastrointestinal function, lower blood pressure, and regulate metabolic abnormalities, but it is not clear whether it acts on MH by increasing SCFA and, if so, how. In this research, it was observed that Dendrobium officinale ultrafine powder (DOFP) could lower blood pressure and improve lipid abnormalities in ACHSFD-induced MH model rats. Moreover, DOFP was found to improve the intestinal flora and increased the SCFA level in feces and serum, as well as increased the expressions of GPCR43/41 and eNOS and the nitric oxide (NO) level. An experiment on isolated aorta rings revealed that DOFP improved the vascular endothelial relaxation function in MH rats, and this effect could be blocked by the eNOS inhibitor l-NAME. These experimental results suggest that DOFP improved the intestinal flora and increased the production, transportation, and utilization of SCFA, activated the intestinal-vascular axis SCFA-GPCR43/41 pathway, improved vascular endothelial function, and finally lowered blood pressure in MH model rats. This research provides a new focus for the mechanism of the effect of DOFP against MH by triggering the enteric-origin SCFA-GPCR43/41 pathway.


Assuntos
Dendrobium/química , Suplementos Nutricionais , Ácidos Graxos Voláteis/metabolismo , Hipertensão/dietoterapia , Receptores Acoplados a Proteínas G/metabolismo , Animais , Pressão Sanguínea , Colesterol/sangue , Dieta , Modelos Animais de Doenças , Fezes , Microbioma Gastrointestinal , Trato Gastrointestinal/metabolismo , Fígado/patologia , Masculino , Óxido Nítrico/sangue , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos , Transdução de Sinais
6.
Artigo em Inglês | MEDLINE | ID: mdl-35003313

RESUMO

MATERIALS AND METHODS: After intragastric administration of DOFP for 3 weeks, the rat UC model was made by the administration of 4% oral DSS solution for one week, and the drug was given at the same time. During the experiment, the disease activity index (DAI) score of the rats was regularly computed. At the end of the experiment, the blood routine indexes of rats were obtained. The histopathological changes in the colon were monitored by hematoxylin-eosin (H&E) and PAS staining and observation of ultrastructural changes in the colon by transmission electron microscope. Occludin expression in the colon was monitored by Western blot, the expression of claudin-1 and ZO-1 in the colon was detected by immunofluorescence, and the expression of TNF-α, IL-6, and IL-1ß in the colon was detected by immunohistochemistry. RESULTS: The results firstly indicated that DOFP could significantly alleviate the signs and symptoms of the DSS-induced rats UC model, which manifested as improvement of body weight loss, increase of colon length, and improvement of the symptoms of diarrhea and hematochezia. Then, results from histopathology, blood routine examination, and transmission electron microscope analysis further implied that DOFP could dramatically reduce inflammatory cell infiltration and restore intestinal epithelial barrier integrity. In addition, the experiments of Western Blot analysis, immunofluorescence, and PAS staining also further confirmed that DOFP could markedly increase related protein expressions of the intestinal barrier and mucus barrier, as the expression of occludin, claudin-1, and ZO-1 in the colon significantly decreased. The experiments of immunohistochemistry confirmed that DOFP could markedly decrease protein expression levels of inflammatory cytokines TNF-α, IL-6, and IL-1ß. CONCLUSION: DOFP notably alleviated inflammatory lesions, repaired the colon mucosa damage by promoting the expression of tight junction proteins occludin, claudin-1, and ZO-1 and inhibiting the release of inflammatory factors TNF-α, IL-6, and IL-1ß, and finally achieved the purpose of treating UC.

7.
Biomed Pharmacother ; 132: 110765, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33120237

RESUMO

AIM: Hyperuricemia (HUA) is a metabolic disease caused by the overproduction or underexcretion of uric acid (UA). Our previous study found that treatment with Dendrobium officinalis six nostrum (DOS) led to a significant reduction in serum UA (SUA) by inhibiting UA production and promoting UA excretion in a rat model of HUA induced by potassium oxonate (PO) and high-fat sorghum feed. In this study, we aimed to further investigate the effects of DOS on UA excretion by the kidney and intestine to explore whether DOS protects against histopathological changes, and to elucidate its possible mechanisms of action in a lipid emulsion (LE)-induced rat model of HUA. METHODS: The main chemical constituents of DOS were determined to be acteoside and astilbin by high-performance liquid chromatography (HPLC). Three different doses of DOS (3.3, 6.6, and 13.2 g/kg/day) were given to rats daily after induction of HUA by oral administration of LE for 8 weeks. The levels of creatinine (Cr) in serum and urine and UA in serum, urine, and feces were measured by an automatic biochemical analyzer. The expression of TLR4, NF-κB and urate transport-related transporters (URAT1, ABCG2, and PDZK1) in kidney was measured by Western blot (WB). Intestinal urate transporters (ABCG2 and GLUT9) expression was assayed by IHC and WB. Serum LPS and renal inflammatory factors (IL-6, IL-8 and TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA) kits. Hematoxylin and eosin (H&E) staining was used to assess renal histological changes. RESULTS: DOS treatment significantly reduced the SUA and SCr levels by increasing urine volume, 24 h urine uric acid (UUA), fecal UA (FUA), urine creatinine (UCr), and fractional excretion of UA (FEUA) levels in hyperuricemic rats. Moreover, DOS effectively regulated URAT1, PDZK1, and ABCG2 protein levels in the kidney, as well as restored protein levels of GLUT9 and ABCG2 in the intestine. DOS markedly reduced serum LPS anddown-regulated renal TLR4 and NF-κB protein levels to suppress IL-6, IL-8, and TNF-α secretion. It also improved renal inflammation in hyperuricemic rats. In addition, DOS attenuated histopathological changes in the kidneys of LE-induced rats. HPLC analysis showed levels of acteoside and astilbin of 1.39 mg/g and 0.72 mg/g in DOS, respectively. CONCLUSION: DOS has anti-hyperuricemic and anti-inflammatory effects in a rat model of HUA. The molecular mechanism appears to involve the regulation of urate transport-related transporters including renal ABCG2, URAT1, and PDZK1, and intestinal GLUT9 and ABCG2, as well as the inhibition of the LPS/TLR4/NF-κB signaling to reduce IL-6, IL-8, and TNF-α secretion in hyperuricemic rats.


Assuntos
Dendrobium/química , Hiperuricemia/prevenção & controle , Extratos Vegetais/farmacologia , Ácido Úrico/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Emulsões , Nefropatias/fisiopatologia , Nefropatias/prevenção & controle , Lipídeos/efeitos adversos , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley
8.
BMC Complement Med Ther ; 20(1): 265, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859182

RESUMO

BACKGROUND: Ganluyin (GLY) is a famous classical prescription with a long history of use as a treatment for inflammatory conditions such as chronic pharyngitis (CP) in many parts of China. However, it has not been developed as a modern pharmaceutic and its anti-inflammatory mechanisms remain unclear. The aim of this study was to assess the anti-inflammatory efficacy of GLY and potential mechanisms in a rat model of CP. METHODS: The chemical profile of GLY was analyzed by HPLC-UV. We used a mouse model of ear edema and a rat model of paw edema. Specifically, xylene was used to induce edema on the surface of one ear in mice, and carrageenan was injected subcutaneously into the right hind paws of rats to induce paw edema. The paw thickness, ear weight, and ear perfusion were measured and recorded. The CP model in rats was induced by irritating the throat with 5% ammonia and was used to evaluate the therapeutic efficacy of GLY. Levels of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE2) were measured by ELISA in serum, and protein expression of cyclooxygenase-2 (COX-2) and nuclear factor kappa-B p65 (NF-κB p65) in the throat were detected by immunohistochemistry and Western blot to evaluate the anti-inflammatory mechanism of GLY. Hematological assays were also conducted. RESULTS: There were four flavonoids identified in GLY: naringin, neohesperidin, baicalin, and wogonoside. The oral administration of GLY showed a significant inhibitory effect on xylene-induced ear swelling and ear blood flow in mice and significantly ameliorated rat right hind paw edema at doses of 6.2 and 12.4 g/kg. Mechanistic studies found that the anti-inflammatory activity of GLY was related to the inhibition of pro-inflammatory cytokines such as IL-1ß, IL-6, TNF-α, and PGE2 and that GLY reduced the expression of COX-2 and NF-κB p65 proteins in the throat, attenuated throat injury, and reduced inflammatory exudates. Hematological analysis showed that treatment with GLY prevented increases in white blood cell (WBC), neutrophil (NEUT), lymphocyte (LYMPH) and monocyte (MONO) levels. CONCLUSIONS: These studies indicated that GLY has beneficial anti-inflammatory effects on CP and that it acts through reducing pro-inflammatory factors such as IL-1ß, IL-6, TNF-α, and PGE2, as well as decreasing WBC, NEUT, LYMPH and MONO levels and decreasing the expression of COX-2 and NF-κB p65 proteins. These findings may lay the groundwork for further studies of GLY as a suitable candidate for the treatment of inflammatory diseases such as CP.


Assuntos
Anti-Inflamatórios/farmacologia , Medicina Tradicional Chinesa , Faringite/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos ICR , Estrutura Molecular , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley
9.
Artigo em Inglês | MEDLINE | ID: mdl-32617111

RESUMO

Suanzaoren decoction (SZRT), a classic Chinese herbal prescription, has been used as a treatment for insomnia for more than a thousand years. However, recent studies have found no significant effects of SZRT as a treatment for insomnia caused by gastric discomfort. Herein, we studied the effects of modified Suanzaoren decoction (MSZRD) on gastrointestinal disorder-related insomnia. The main constituents of MSZRD were spinosin (2.21 mg/g) and 6-feruloylspinosin (0.78 mg/g). A pentobarbital-induced animal model of insomnia showed that MSZRD shortened sleep latency and prolonged sleep time of the male Institute of Cancer Research (ICR) mice treated for 7 days with oral MSZRD. Sprague-Dawley male rats were treated daily with oral MSZRD or placebo for 11 days and then deprived of sleep for the last 4 days to establish a model of insomnia. Of note, MSZRD-treated animals had significantly improved body weight, organ index scores, and fecal moisture relative to placebo-treated animals, as well as reduced temperature. Sleep-deprived rats exhibited more exploratory behaviors in an open-field anxiety test; however, this effect was significantly reduced in MSZRD-treated animals. We found that MSZRD treatment decreased gastric acid pH, decreased the production of gastrin, pepsin, and Orexin-A, and increased the expression of MTL and CCK-8. Importantly, serum GABA concentration was increased by treatment with MSZRD, as reflected by a decreased Glu/GABA ratio. Treated animals had increased the expression of GAD1, GABARA1, and CCKBR but decreased the expression of Orexin R1. In summary, these results suggest that MSZRD has soporific and gastroprotective effects that may be mediated by differential expression of CCK-8 and Orexin-A.

10.
Zhongguo Zhong Yao Za Zhi ; 39(24): 4769-72, 2014 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-25898575

RESUMO

To reveal the variation of polysaccharides and alcohol-soluble extract contents of Dendrobium officinale, the polysaccharides and alcohol-soluble extracts contents of three D. officinale strains were determined by phenol-sulfuric acid method and hot-dip method, respectively. The results showed that the contents of polysaccharides and alcohol-soluble extracts and their total content were significantly different among D. officinale samples collected in different periods, and the variations were closely related to the phenology of D. officinale. Additionally, the quality variation of polysaccharides was closely related to the flowering of D. officinale, while the alcohol-soluble extracts was closely associated to the formation and germination of buds. According to the dynamic variation of these two compounds, it is more reasonable to harvest D. officinale at biennials pre-bloom than at specific harvesting month considering polysaccharides content. It is better to harvest before the germination of buds considering alcohol-soluble extracts. While with regards to both polysaccharides and alcohol-soluble extract, it is better to harvest this plant at the period from the sprouting to pre-bloom next year.


Assuntos
Dendrobium/química , Extratos Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação
11.
Zhongguo Zhong Yao Za Zhi ; 38(4): 475-80, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23713267

RESUMO

The standandized cultivation of Chinese medicinal materials is based on variety. With the rapid development of Dendrobium officinale industry and increasing demand of improved varieties, many studies have concentrated on the variety breeding of D. officinale and subsequently achieved remarkable success. This paper systematically expounds the research progress of D. officinale breeding, e. g. the collection and differentiated evaluation for germplasm, theory and practice for variety breeding, tissue culture and efficient production with low-carbon for germchit, and DNA molecular marker-assisted breeding, and then indicates the main problems of the current breeding of D. officinale. Furthermore, the priorities and keys for the further breeding of D. officinale have been pointed out.


Assuntos
Cruzamento/métodos , Dendrobium/genética , Carbono/metabolismo , Impressões Digitais de DNA , Dendrobium/química , Dendrobium/citologia , Dendrobium/metabolismo , Medicamentos de Ervas Chinesas , Controle de Qualidade
12.
Zhongguo Zhong Yao Za Zhi ; 38(4): 481-4, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23713268

RESUMO

Since the beginning of the new century, the artificial cultivation of Dendrobium officinale has made a breakthrough progress. This paper systematically expounds key technologies, main features and cautions of the cultivation modes e.g. bionic-facility cultivation, the original ecological cultivation, and potting cultivation for D. officinale, which can provide useful information for the development and improvement of D. officinale industry.


Assuntos
Técnicas de Cultura/métodos , Dendrobium/crescimento & desenvolvimento , Animais , Biomimética , Técnicas de Cultura/instrumentação , Dendrobium/química , Dendrobium/microbiologia , Medicamentos de Ervas Chinesas , Controle de Pragas , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle
13.
Zhongguo Zhong Yao Za Zhi ; 38(4): 524-7, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23713277

RESUMO

OBJECTIVE: To reveal the quality variation of polysaccharide in Dendrobium officinale by post-harvest processing and extraction methods, and provide a basis for post-harvest processing and clinical and hygienical applications of Tiepifengdou (Dendrobii Officinalis Caulis). METHOD: The content of polysaccharides were studied by 4 post-harvest processing methods, i. e. drying by drying closet, drying after scalding by boiling water, drying while twisting, and drying while twisting after scalding by boiling water. And a series of temperatures were set in each processing procedure. An orthogonal test L9 (3(4)) with crushed degrees, solid-liquid ratio, extraction time and extraction times as factors were designed to analyze the dissolution rate of polysaccharides in Tiepifengdou processed by drying while twisting at 80 degrees C. RESULT: The content of polysaccharides was ranged from 26.59% to 32.70% in different samples processed by different processing methods, among which drying while twisting at 80 degrees C and 100 degrees C respectively were the best. Crushed degree was the most important influence on the dissolution rate of polysaccharides. The dissolution rate of polysaccharides was extremely low when the sample was boiled directly without crushing and sieving. CONCLUSION: Drying while twisting at 80 degrees C was the best post-harvest processing method, which can help to dry the fresh herbs and improve the accumulation of polysaccharides. Boiling the uncrushed Tiepifengdou for a long time as traditional method could not fully extract polysaccharides, while boiling the crushed Tiepifengdou can efficiently extract polysaccharides.


Assuntos
Fracionamento Químico/métodos , Dendrobium/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Polissacarídeos/análise , Dendrobium/crescimento & desenvolvimento , Dessecação , Modelos Lineares , Temperatura , Água/química
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