RESUMO
Bone metastasis resulting from advanced breast cancer causes osteolysis and increases mortality in patients. Kalkitoxin (KT), a lipopeptide toxin derived from the marine cyanobacterium Moorena producens (previously Lyngbya majuscula), has an anti-metastatic effect on cancer cells. We verified that KT suppressed cancer cell migration and invasion in vitro and in animal models in the present study. We confirmed that KT suppressed osteoclast-soup-derived MDA-MB-231 cell invasion in vitro and induced osteolysis in a mouse model, possibly enhancing/inhibiting metastasis markers. Furthermore, KT inhibits CXCL5 and CXCR2 expression, suppressing the secondary growth of breast cancer cells on the bone, brain, and lungs. The breast-cancer-induced osteolysis in the mouse model further reveals that KT plays a protective role, judging by micro-computed tomography and immunohistochemistry. We report for the first time the novel suppressive effects of KT on cancer cell migration and invasion in vitro and on MDA-MB-231-induced bone loss in vivo. These results suggest that KT may be a potential therapeutic drug for the treatment of breast cancer metastasis.
Assuntos
Osteólise , Animais , Camundongos , Osteólise/metabolismo , Microtomografia por Raio-X , Osteoclastos/metabolismo , Lipídeos/farmacologia , Movimento Celular , Linhagem Celular Tumoral , Metástase NeoplásicaRESUMO
An imbalance of osteoclasts and osteoblasts can result in a variety of bone-related diseases, including osteoporosis. Thus, decreasing the activity of osteoclastic bone resorption is the main therapeutic method for treating osteoporosis. 2E-Decene-4, 6-diyn-1-ol-acetate (DDA) is a natural bioactive compound with anti-inflammatory and anti-cancer properties. However, its effects on osteoclastogenesis are unknown. Murine bone marrow-derived macrophages (BMMs) or RAW264.7 cells were treated with DDA, followed by evaluation of cell viability, RANKL-induced osteoclast differentiation, and pit formation assay. Effects of DDA on RANKL-induced phosphorylation of MAPKs were assayed by western blot analysis. Expression of osteoclast-specific genes was examined with reverse transcription-PCR (RT-PCR) and western blot analysis. In this study, DDA significantly inhibited RANKL-induced osteoclast differentiation in RAW264.7 cells as well as in BMMs without cytotoxicity. DDA also strongly blocked the resorbing capacity of BMM on calcium phosphate-coated plates. DDA inhibited RANKL-induced phosphorylation of ERK, JNK and p38 MAPKs, as well as expression of c-Fos and NFATc1, which are essential transcription factors for osteoclastogenesis. In addition, DDA decreased expression levels of osteoclastogenesis-specific genes, including matrix metalloproteinase-9 (MMP-9), tartrate-resistant acid phosphatase (TRAP), and receptor activator of NF-κB (RANK) in RANKL-induced RAW264.7 cells. Collectively, these findings indicated that DDA attenuates RANKL-induced osteoclast formation by suppressing the MAPKs-c-Fos-NFATc1 signalling pathway and osteoclast-specific genes. These results indicate that DDA may be a potential candidate for bone diseases associated with abnormal osteoclast formation and function.
Assuntos
Produtos Biológicos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Genes fos/fisiologia , Macrófagos/efeitos dos fármacos , Fatores de Transcrição NFATC/metabolismo , Osteogênese/efeitos dos fármacos , Animais , Aster/química , Produtos Biológicos/química , Diferenciação Celular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Genes fos/genética , Camundongos , Fatores de Transcrição NFATC/genética , Osteoclastos , Ligante RANK/genética , Ligante RANK/metabolismo , Células RAW 264.7RESUMO
Osteoclasts, bone-specified multinucleated cells produced by monocyte/macrophage, are involved in numerous bone destructive diseases such as arthritis, osteoporosis, and inflammation-induced bone loss. The osteoclast differentiation mechanism suggests a possible strategy to treat bone diseases. In this regard, we recently examined the in vivo impact of kalkitoxin (KT), a marine product obtained from the marine cyanobacterium Moorena producens (previously Lyngbya majuscula), on the macrophage colony-stimulating factor (M-CSF) and on the receptor activator of nuclear factor κB ligand (RANKL)-stimulated in vitro osteoclastogenesis and inflammation-mediated bone loss. We have now examined the molecular mechanism of KT in greater detail. KT decreased RANKL-induced bone marrow-derived macrophages (BMMs) tartrate-resistant acid phosphatase (TRAP)-multinucleated cells at a late stage. Likewise, KT suppressed RANKL-induced pit area and actin ring formation in BMM cells. Additionally, KT inhibited several RANKL-induced genes such as cathepsin K, matrix metalloproteinase (MMP-9), TRAP, and dendritic cell-specific transmembrane protein (DC-STAMP). In line with these results, RANKL stimulated both genes and protein expression of c-Fos and nuclear factor of activated T cells (NFATc1), and this was also suppressed by KT. Moreover, KT markedly decreased RANKL-induced p-ERK1/2 and p-JNK pathways at different time points. As a result, KT prevented inflammatory bone loss in mice, such as bone mineral density (BMD) and osteoclast differentiation markers. These experiments demonstrated that KT markedly inhibited osteoclast formation and inflammatory bone loss through NFATc1 and mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, KT may have potential as a treatment for destructive bone diseases.
Assuntos
Reabsorção Óssea/tratamento farmacológico , Lipídeos/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Tiazóis/uso terapêutico , Actinas/genética , Actinas/metabolismo , Animais , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/metabolismo , Catepsina K/genética , Catepsina K/metabolismo , Sobrevivência Celular , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Janus Quinases/metabolismo , Lipídeos/farmacologia , Lipopolissacarídeos/toxicidade , Lyngbya/química , Sistema de Sinalização das MAP Quinases/genética , Fator Estimulador de Colônias de Macrófagos/antagonistas & inibidores , Fator Estimulador de Colônias de Macrófagos/metabolismo , Fator Estimulador de Colônias de Macrófagos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Fatores de Transcrição NFATC/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Osteoclastos/metabolismo , Osteogênese/genética , Fosforilação , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ligante RANK/antagonistas & inibidores , Ligante RANK/metabolismo , Ligante RANK/farmacologia , Fosfatase Ácida Resistente a Tartarato/genética , Fosfatase Ácida Resistente a Tartarato/metabolismo , Tiazóis/farmacologiaRESUMO
Introduction: Overweight and obesity are rapidly increasing worldwide, posing a significant global health challenge. Medical students are at a higher risk of developing obesity due to factors such as a sedentary lifestyle, inadequate physical activity, unhealthy eating patterns, elevated stress levels, and the extensive amount of information they need to learn. The aim of this study was to find out the prevalence of overweight among medical students of a medical college. Methods: A descriptive cross-sectional study was conducted among medical students of a medical college from 5 October 2022 to 10 November 2022 after obtaining ethical approval from the Institutional Review Committee. Height in meters and weight in kilograms of students were measured to calculate body mass index. A convenience sampling method was used. The point estimate at a 95% Confidence Interval was calculated. Results: Among 261 medical students, 43 (16.47%) (11.97-20.97, 95% Confidence Interval) were overweight. Among them, 32 (74.41%) males and 11 (25.58%) females were overweight respectively. Conclusions: The prevalence of overweight among medical students is lower than in other studies done in similar settings. Keywords: body mass index; obesity; overweight; prevalence.
Assuntos
Sobrepeso , Estudantes de Medicina , Masculino , Feminino , Humanos , Sobrepeso/epidemiologia , Estudos Transversais , Obesidade/epidemiologia , Índice de Massa Corporal , PrevalênciaRESUMO
The harmful effects of fine particulate matter ≤2.5 µm in size (PM2.5) on human health have received considerable attention. However, while the impact of PM2.5 on the respiratory and cardiovascular systems has been well studied, less is known about the effects on stem cells in the bone marrow (BM). With an emphasis on the invasive characteristics of PM2.5, this review examines the current knowledge of the health effects of PM2.5 exposure on BM-residing stem cells. Recent studies have shown that PM2.5 enters the circulation and then travels to distant organs, including the BM, to induce oxidative stress, systemic inflammation and epigenetic changes, resulting in the reduction of BM-residing stem cell survival and function. Understanding the broader health effects of air pollution thus requires an understanding of the invasive characteristics of PM2.5 and its direct influence on stem cells in the BM. As noted in this review, further studies are needed to elucidate the underlying processes by which PM2.5 disturbs the BM microenvironment and inhibits stem cell functionality. Strategies to prevent or ameliorate the negative effects of PM2.5 exposure on BM-residing stem cells and to maintain the regenerative capacity of those cells must also be investigated. By focusing on the complex relationship between PM2.5 and BM-resident stem cells, this review highlights the importance of specific measures directed at safeguarding human health in the face of rising air pollution.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Células-Tronco Mesenquimais , Humanos , Material Particulado/efeitos adversos , Poluentes Atmosféricos/efeitos adversos , Medula Óssea , Poluição do Ar/efeitos adversos , Exposição AmbientalRESUMO
BACKGROUND: Kalkitoxin (KT) is an active lipopeptide isolated from the cyanobacterium Lyngbya majuscula found in the bed of the coral reef. Although KT suppresses cell division and inflammation, KT's mechanism of action in vascular smooth muscle cells (VSMCs) is unidentified. Therefore, our main aim was to investigate the impact of KT on vascular calcification for the treatment of cardiovascular disease. OBJECTIVES: Using diverse calcification media, we studied the effect of KT on VSMC calcification and the underlying mechanism of this effect. METHODS: VSMC was isolated from the 6 weeks ICR mice. Then VSMCs were treated with different concentrations of KT to check the cell viability. Alizarin red and von Kossa staining were carried out to examine the calcium deposition on VSMC. Thoracic aorta of 6 weeks mice were taken and treated with different concentrations of KT, and H and E staining was performed. Real-time polymerase chain reaction and western blot were performed to examine KT's effect on VSMC mineralization. Calcium deposition on VSMC was examined with a calcium deposition quantification kit. RESULTS: Calcium deposition, Alizarin red, and von Kossa staining revealed that KT reduced inorganic phosphate-induced calcification phenotypes. KT also reduced Ca++-induced calcification by inhibiting genes that regulate osteoblast differentiation, such as runt-related transcription factor 2 (RUNX-2), SMAD family member 4, osterix, collagen 1α, and osteopontin. Also, KT repressed Ca2+-induced bone morphogenetic protein 2, RUNX-2, collagen 1α, osteoprotegerin, and smooth muscle actin protein expression. Likewise, Alizarin red and von Kossa staining showed that KT markedly decreased the calcification of ex vivo ring formation in the mouse thoracic aorta. CONCLUSIONS: This experiment demonstrated that KT decreases vascular calcification and may be developed as a new therapeutic treatment for vascular calcification and arteriosclerosis.
Assuntos
Calcificação Vascular , Animais , Camundongos , Cálcio/metabolismo , Células Cultivadas , Colágeno/metabolismo , Camundongos Endogâmicos ICR , Músculo Liso Vascular/metabolismo , Transdução de Sinais , Calcificação Vascular/prevenção & controle , Calcificação Vascular/tratamento farmacológico , Calcificação Vascular/metabolismo , Calcificação Vascular/veterináriaRESUMO
Introduction: Anaemia is one of the most common conditions which affects a significant proportion of pregnant women worldwide. These patients may have adverse effects on both the mother and the developing fetus. Detecting and timely treating anaemia in pregnancy help in the overall improvement of maternal and fetal health. The aim of the study was to find out the prevalence of low-birth-weight among term newborns born to anaemic pregnant women admitted to the Department of Obstetrics and Gynecology in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among pregnant women who were diagnosed with anaemia and admitted for delivery in the Department of Obstetrics and Gynecology after obtaining ethical approval from the Institutional Review Committee. Data was collected from 10 December 2022 to 10 March 2023. Convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Among 300 newborns, the prevalence of low-birth-weight was 106 (35.33%) (29.92-40.74, 95% Confidence Interval). Among 106 newborn, 64 (60.37%) were male and 42 (39.62%) were female. Conclusions: The prevalence of low-birth-weight among newborns born to term anaemic pregnant women admitted to the Department of Obstetrics and Gynecology in a tertiary care centre was found to be higher than in studies done in a similar settings. Keywords: anaemia; infant; low birth weight; morbidity; pregnancy.
Assuntos
Anemia , Ginecologia , Complicações Hematológicas na Gravidez , Lactente , Recém-Nascido , Feminino , Gravidez , Humanos , Masculino , Gestantes , Estudos Transversais , Centros de Atenção Terciária , Complicações Hematológicas na Gravidez/epidemiologia , Recém-Nascido de Baixo Peso , Anemia/epidemiologia , PartoRESUMO
PURPOSE: Aloe-emodin (AE), a natural anthraquinone abundant in aloe plants and rhubarb (Rheum rhabarbarum), has long been used to treat chronic inflammatory diseases. However, AE's underlying mechanisms in periodontal inflammation have not been fully elucidated. Acidic mammalian chitinase (AMCase) is a potential biomarker involved in bone remodeling. This study aimed to evaluate AE's effect on periodontitis in rats and investigate AMCase expression. METHODS: Eighteen Sprague-Dawley rats were separated into the following groups: healthy (group 1), disease (group 2), vehicle (group 3), AE high-dose (group 4), and AE low-dose (group 5). Porphyromonas gingivalis ligatures were placed in rats (groups 2-5) for 7 days. Groups 4 and 5 were then treated with AE for an additional 14 days. Saliva was collected from all groups, and probing pocket depth was measured in succession. Periodontal pocket tissues were subjected to histomorphometric analysis after the rats were sacrificed. Bone marrow-derived macrophages and murine macrophages were stimulated with receptor activator of nuclear factor-κB ligand (RANKL) and treated with different concentrations of AE. AMCase expression was detected from the analysis of saliva, periodontal pocket tissues, and differentiated osteoclasts. RESULTS: Among rats with P. gingivalis-induced periodontitis, the alveolar bone resorption levels and periodontal pocket depth were significantly reduced after treatment with AE. AMCase protein expression was significantly higher in the disease group than in the healthy control (P<0.05). However, AE inhibited periodontal inflammation by downregulating AMCase expression in saliva and periodontal pocket tissue. AE significantly reduced RANKL-stimulated osteoclastogenesis by modulating AMCase (P<0.05). CONCLUSIONS: AE decreases alveolar bone loss and periodontal inflammation, suggesting that this natural anthraquinone has potential value as a novel therapeutic agent against periodontal disease.
RESUMO
BACKGROUND: In lipopolysaccharide-induced RAW264.7 cells, Aster tataricus (AT) inhibits the nuclear factor kappa-light-chain-enhancer of activated B cells and MAPKs pathways and critical pathways of osteoclast development and bone resorption. OBJECTIVES: This study examined how aster saponin A2 (AS-A2) isolated from AT affects the processes and function of osteoclastogenesis induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in RAW264.7 cells and bone marrow macrophages (BMMs). METHODS: The cell viability, tartrate-resistant acid phosphatase staining, pit formation assay, polymerase chain reaction, and western blot were carried out to determine the effects of AS-A2 on osteoclastogenesis. RESULTS: In RAW264.7 and BMMs, AS-A2 decreased RANKL-initiated osteoclast differentiation in a concentration-dependent manner. In AS-A2-treated cells, the phosphorylation of ERK1/2, JNK, and p38 protein expression were reduced considerably compared to the control cells. In RAW264.7 cells, AS-A2 suppressed the RANKL-induced activation of osteoclast-related genes. During osteoclast differentiation, AS-A2 suppressed the transcriptional and translational expression of NFATc1 and c-Fos. AS-A2 inhibited osteoclast development, reducing the size of the bone resorption pit area. CONCLUSION: AS-A2 isolated from AT appears to be a viable therapeutic therapy for osteolytic illnesses, such as osteoporosis, Paget's disease, and osteogenesis imperfecta.
Assuntos
Reabsorção Óssea , Saponinas , Animais , Células da Medula Óssea/metabolismo , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Reabsorção Óssea/veterinária , Diferenciação Celular , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/farmacologia , Mitógenos/metabolismo , Mitógenos/farmacologia , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Fatores de Transcrição NFATC/farmacologia , Osteoclastos/metabolismo , Osteogênese/fisiologia , Ligante RANK/metabolismo , Ligante RANK/farmacologia , Saponinas/farmacologia , Transdução de SinaisRESUMO
The Himalayan red panda (Ailurus fulgens), a recently confirmed distinct species in the red panda genus, is distributed in Nepal, India, Bhutan, and south Tibet. Nepal represents the westernmost distribution of the Himalayan red panda. This study aims to determine important habitat features influencing the distribution of red panda and recommend possible habitat corridors. This manuscript described current potential habitat of 3,222 km2 with the relative abundance of 3.34 signs/km in Nepal. Aspect, canopy cover, bamboo cover, and distance to water were the important habitat attributes. It suggested five potential corridors in western Nepal. Overall, the study has important implications for conservation of the Himalayan red panda in western distribution range.
RESUMO
Panax ginseng has a wide range of activities including a neuroprotective effect, skin protective effects, enhanced DNA repairing, anti-diabetic activity, and protective effects against vascular inflammation. In the present study, we sought to discover the inhibitory effects of a mixture of natural products containing Panax ginseng, Ziziphus jujube, Rubi fructus, Artemisiae asiaticae and Scutellaria baicalensis (PZRAS) on osteoclastogenesis and bone remodeling, as neither the effects of a mixture containing Panax ginseng extract, nor its molecular mechanism on bone inflammation, have been clarified yet. PZRAS upregulated the levels of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSH-R) and glutathione peroxidase (GSH-Px) and reduced malondialdehyde (MDA) in LPS-treated RAW264.7 cells. Moreover, treatment with PZRAS decreased the production of IL-1ß and TNF-α. PZRAS also inhibited osteoclast differentiation through inhibiting osteoclastspecific genes like MMP-2, 9, cathepsin K, and TRAP in RANKL-treated RAW264.7 cells. Additionally, PZRAS has inhibitory functions on the RANKL-stimulated activation of ERK and JNK, which lead to a decrease in the expression of NFATc1 and c-Fos. In an in vivo study, bone resorption induced by LPS was recovered by treatment with PZRAS in bone volume per tissue volume (BV/TV) compared to control. Furthermore, the ratio of eroded bone surface of femurs was significantly increased in LPStreated mice compared to vehicle group, but this ratio was significantly reversed in PZRAS-treated mice. These results suggest that PZRAS could prevent or treat disorders with abnormal bone loss.
Assuntos
Reabsorção Óssea/prevenção & controle , Inflamação/prevenção & controle , Osteogênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Catepsina K/genética , Catepsina K/metabolismo , Diferenciação Celular/efeitos dos fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolissacarídeos/toxicidade , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ligante RANK/genética , Ligante RANK/metabolismo , Células RAW 264.7 , Fosfatase Ácida Resistente a Tartarato/genética , Fosfatase Ácida Resistente a Tartarato/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
An imbalance between bone resorption and bone formation leads to several kinds of bone diseases such as rheumatoid arthritis, osteoporosis and Paget's disease. The imbalance between bone formations relative to bone resorption is responsible in bone remodeling. Several studies have suggested that macrolactin A (MA) has potent anti-inflammatory, anti-cancer and anti-angiogenic effects in various cell types. We investigate whether macrolactin A (MA) could inhibit bone loss and enhance bone formation. We used bone marrow monocytes/macrophages (BMMs) cells to study osteoclast activity and MC3T3-E1 cells to study osteoblast activity. MA suppressed tartrate resistant acid phosphatase (TRAP) positive multinucleated cells in a concentration-dependent manner, as well as at a specific time point. MA markedly reduced bone resorption activity and F-actin ring formation. Moreover, MA markedly suppressed receptor activator of nuclear factor k-B ligand (RANKL)-induced osteoclastogenic marker genes and transcription factors in-vitro. MA repressed osteoclast differentiation via activation of the phosphoinositide kinase-3/Akt, extracellular signal-regulated kinase 1/2 (ERK 1/2), c-Jun N-terminal kinase (JNK), nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) and c-Fos signaling pathways. MA enhanced pre-osteoblast cell differentiation on mineralization activity, alkaline phosphatase (ALP) activity, and the expression of osteoblastogenic markers including osterix, RUNX-2, SMAD4, BMP-2, and ALP. Importantly, MA repressed lipopolysaccharide (LPS)-induced inflammatory bone loss in mice as shown by TRAP staining of femurs and µCT analysis. Therefore, MA could be a promising candidate for the inhibition and management of osteoporosis, arthritis, and bone lytic diseases.
Assuntos
Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Macrolídeos/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteoporose/prevenção & controle , Células 3T3 , Animais , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Regulação da Expressão Gênica , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoporose/induzido quimicamente , Osteoporose/metabolismo , Osteoporose/patologia , Transdução de SinaisRESUMO
The Himalayan red panda is an endangered mammal endemic to Eastern Himalayan and South Western China. Data deficiency often hinders understanding of their spatial distribution and habitat use, which is critical for species conservation planning. We used sign surveys covering the entire potential red panda habitat over 22,453 km2 along the mid-hills and high mountains encompassing six conservation complexes in Nepal. To estimate red panda distribution using an occupancy framework, we walked 1,451 km along 446 sampled grid cells out of 4,631 grid cells in the wet season of 2016. We used single-species, single-season models to make inferences regarding covariates influencing detection and occupancy. We estimated the probability of detection and occupancy based on model-averaging techniques and drew predictive maps showing site-specific occupancy estimates. We observed red panda in 213 grid cells and found covariates such as elevation, distance to water sources, and bamboo cover influencing the occupancy. Red panda detection probability [Formula: see text] estimated at 0.70 (0.02). We estimated red panda site occupancy (sampled grid cells) and landscape occupancy (across the potential habitat) [Formula: see text] at 0.48 (0.01) and 0.40 (0.02) respectively. The predictive map shows a site-specific variation in the spatial distribution of this arboreal species along the priority red panda conservation complexes. Data on their spatial distribution may serve as a baseline for future studies and are expected to aid in species conservation planning in priority conservation complexes.
Assuntos
Ailuridae/fisiologia , Animais , Conservação dos Recursos Naturais , Ecossistema , Nepal , Estações do AnoRESUMO
Vascular calcification increases the risk of morbidity and mortality in patients with cardiovascular diseases, chronic kidney diseases, and diabetes. However, viable therapeutic methods to target vascular calcification are limited. Aloe-emodin (AE), an anthraquinone is a natural compound found in the leaves of Aloe-vera. In this study, we investigated the underlying mechanism of AE in the calcification of vascular smooth muscle cells (VSMCs) and murine thoracic aorta. We demonstrate that AE repressed not only the phenotypes of Ca2+ induced calcification but also level of calcium in VSMCs. AE has no effect on cell viability in VSMC cells. Alizarin red, von Kossa stainings and calcium quantification showed that Ca2+ induced vascular calcification is significantly decreased by AE in a concentration-dependent manner. In contrast, AE attenuated Ca2+ induced calcification through inhibiting osteoblast differentiation genes such as SMAD4, collagen 1α, osteopontin (OPN), Runt-related transcription factor (RUNX-2) and Osterix. AE also suppressed Ca2+ induced osteoblast-related protein expression including collagen 1α, bone morphogenic protein 2 (BMP-2), RUNX-2 and smooth muscle actin (SMA). Furthermore, Alizarin red, von Kossa stainings and calcium quantification showed that AE significantly inhibited the calcification of ex vivo ring formation in murine thoracic aorta, and markedly inhibited vitamin D3 induced medial aorta calcification in vivo. Taken together, our findings suggest that AE may have therapeutic potential for the prevention of vascular calcification program.
Assuntos
Antraquinonas/farmacologia , Calcificação Fisiológica/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Animais , Aorta Torácica/citologia , Proteína Morfogenética Óssea 2/metabolismo , Cálcio/metabolismo , Masculino , Camundongos Endogâmicos ICR , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/fisiologia , Osteogênese/efeitos dos fármacos , Proteína Smad4/genéticaRESUMO
Red panda Ailurus fulgens, an endangered habitat specialist, inhabits a narrow distribution range in bamboo abundance forests along mountain slopes in the Himalaya and Hengduan Mountains. However, their habitat use may be different in places with different longitudinal environmental gradients, climatic regimes, and microclimate. This study aimed to determine the habitat variables affecting red panda distribution across different longitudinal gradients through a multivariate analysis. We studied habitat selection patterns along the longitudinal gradient in Nepal's Himalaya which is grouped into the eastern, central, and western complexes. We collected data on red panda presence and habitat variables (e.g., tree richness, canopy cover, bamboo abundance, water availability, tree diameter, tree height) by surveys along transects throughout the species' potential range. We used a multimodal inference approach with a generalized linear model to test the relative importance of environmental variables. Although the study showed that bamboo abundance had a major influence, habitat selection was different across longitudinal zones. Both canopy cover and species richness were unimportant in eastern Nepal, but their influence increased progressively toward the west. Conversely, tree height showed a decreasing influence on habitat selection from Eastern to Western Nepal. Red panda's habitat selection revealed in this study corresponds to the uneven distribution of vegetation assemblages and the dry climatic gradient along the eastern-western Himalayas which could be related to a need to conserve energy and thermoregulate. This study has further highlighted the need of importance of bamboo conservation and site-specific conservation planning to ensure long-term red panda conservation.
RESUMO
Red pandas are known to be highly susceptible to endoparasites, which can have a prominent impact on the population dynamics of this endangered species. There are very limited published reports on prevalence and risk of parasites in wild populations of red panda, especially localized reports. This study attempts to provide an in-depth insight of the status of endoparasites in red pandas, which is critical for strengthening conservation efforts. A total of 272 fecal samples were collected through systematic sampling across the red panda distribution range in Nepal and coprological examination was completed using standard techniques. It was followed by an estimation of prevalence and mean intensity of parasites, as well as statistical analysis, which was carried out using R statistical software. Parasite prevalence was documented in 90.80% (n = 247) out of 272 samples examined which includes seven different species along with three genera of parasites belonging to Protozoans (3 species), Cestodes (1 genus, 1 species) and Nematodes (2 genera, 3 species). Nematodes predominated in all infected samples (87.62%). Prevalence of Ancyclostoma duodenale (n = 227, 70.06%), having a mean intensity of 3.45 ± 2.88 individuals per sample, was observed, followed by Ascaris lumbricoides (n = 19, 5.86%) and Entamoeba histolytica (n = 24, 7.41%). Eight variables for assessing the determinants of infestation were tested: protected areas; non-protected areas; aspect; elevation; slope; and distance to water sources, herding stations, and settlements. Only the settlement displayed significant association (ß = -1534e-04, t = - 2.192, p = 0.0293) though each parasite species displayed dissimilar association with different variables. This study indicates the urgent need of improving existing herding practice through habitat zonation, rotational grazing, medication of livestock, and prohibition of open defecation within and around red panda habitat.
RESUMO
In Nepal, the red panda (Ailurus fulgens) has been sparsely studied, although its range covers a wide area. The present study was carried out in the previously untapped Chitwan-Annapurna Landscape (CHAL) situated in central Nepal with an aim to explore current distributional status and identify key habitat use. Extensive field surveys conducted in 10 red panda range districts were used to estimate species distribution by presence-absence occupancy modeling and to predict distribution by presence-only modeling. The presence of red pandas was recorded in five districts: Rasuwa, Nuwakot, Myagdi, Baglung and Dhading. The predictive distribution model indicated that 1,904.44 km2 of potential red panda habitat is available in CHAL with the protected area covering nearly 41% of the total habitat. The habitat suitability analysis based on the probability of occurrence showed only 16.58% (A = 315.81 km2) of the total potential habitat is highly suitable. Red Panda occupancy was estimated to be around 0.0667, indicating nearly 7% (218 km2) of the total habitat is occupied with an average detection probability of 0.4482±0.377. Based on the habitat use analysis, altogether eight variables including elevation, slope, aspect, proximity to water sources, bamboo abundance, height, cover, and seasonal precipitation were observed to have significant roles in the distribution of red pandas. In addition, 25 tree species were documented from red panda sign plots out of 165 species recorded in the survey area. Most common was Betula utilis followed by Rhododendron spp. and Abies spectabilis. The extirpation of red pandas in previously reported areas indicates a need for immediate action for the long-term conservation of this species in CHAL.
Assuntos
Ecossistema , Dinâmica Populacional , Ursidae/fisiologia , Animais , Geografia , Nepal , ProbabilidadeRESUMO
BACKGROUND: The environmental matrices (water, air, and surfaces) play a vital role as reservoirs of Legionella spp. and Pseudomonas aeruginosa (Pseudomonas spp.). Hence, hospital environment control procedures are effective measures for reducing nosocomial infections. AIMS: This study was carried out to explore the profiles of microorganisms in air culture at various wards/units of a tertiary care hospital in Nepal. METHODS: A descriptive cross-sectional study was carried out at various wards/units of a tertiary care hospital in Nepal between January and September 2015 to explore the microbiological burden in inanimate objects. Each week one ward or unit was selected for the study. Bed, tap, the entire room, trolley, computer, phone, rack handles, table, chair, door, stethoscope, oxygen mask, gown, cupboard handles, and wash basins were selected for air culture testing. Ten different wards/units and 77 locations/pieces of equipment were selected for air culture by employing a simple random sampling technique. Information about the organisms was entered into the Statistical Package for the Social Sciences (SPSS) Version 22 (IBM: Armonk, NY) and descriptive analyses were carried out. RESULTS: Staphylococcus aureus (S. aureus), Micrococcus, coagulase negative staphylococcus (CONS), Bacillus, Pseudomonas aeruginosa, yeast, and Acinetobacter were the most commonly detected organisms. In the postoperative ward, S. aureus was the most frequently detected microorganism. Micrococcus was detected in four out of 10 locations. In the x-ray unit, S. aureus was detected in three out of four locations. CONCLUSION: S. aureus, Micrococcus, CONS, Bacillus, Pseudomonas, yeast, and Acinetobacter were the most common organisms detected.
RESUMO
The interplay between bacterial antimicrobial susceptibility, phylogenetics and patient outcome is poorly understood. During a typhoid clinical treatment trial in Nepal, we observed several treatment failures and isolated highly fluoroquinolone-resistant Salmonella Typhi (S. Typhi). Seventy-eight S. Typhi isolates were genome sequenced and clinical observations, treatment failures and fever clearance times (FCTs) were stratified by lineage. Most fluoroquinolone-resistant S. Typhi belonged to a specific H58 subclade. Treatment failure with S. Typhi-H58 was significantly less frequent with ceftriaxone (3/31; 9.7%) than gatifloxacin (15/34; 44.1%)(Hazard Ratio 0.19, p=0.002). Further, for gatifloxacin-treated patients, those infected with fluoroquinolone-resistant organisms had significantly higher median FCTs (8.2 days) than those infected with susceptible (2.96) or intermediately resistant organisms (4.01)(pS. Typhi clade internationally, but there are no data regarding disease outcome with this organism. We report an emergent new subclade of S. Typhi-H58 that is associated with fluoroquinolone treatment failure.
Assuntos
Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ciprofloxacina/farmacologia , Fluoroquinolonas/uso terapêutico , Genótipo , Salmonella typhi/efeitos dos fármacos , Febre Tifoide/tratamento farmacológico , Técnicas de Tipagem Bacteriana , Ceftriaxona/uso terapêutico , Gatifloxacina , Humanos , Nepal , Salmonella typhi/classificação , Salmonella typhi/isolamento & purificação , Análise de Sequência de DNA , Falha de Tratamento , Febre Tifoide/microbiologiaRESUMO
BACKGROUND: Patients with diabetes mellitus have a high risk of atherothrombotic events. Diabetes contributes for initiation and progression of microvascular and macrovascular complications. Shortened activated partial thromboplastin time (aPTT) values may reflect hypercoaguable state, which is associated with increased thrombotic risk and adverse cardiovascular events. Increased level of fibrinogen is common in type II diabetes. The present study was conducted to study the aPTT and fibrinogen levels in diabetics in a tertiary care Teaching Hospital of Nepal. METHODS: Observational study was performed at out-patients visiting Pathology Department at Tribhuvan University Teaching Hospital from August 5 to September 7, 2012. Research protocol was approved by Institutional Review Board at Tribhuvan University Institute of Medicine. Altogether 90 people who came to the hospital during study period and who met inclusion criteria were selected, out of which 72 were diabetics and 18 were normal controls. Diabetic cases were identified via verbal interview with patients themselves and review of laboratory findings and diagnosis performed by their physicians. Diabetics with a diabetic history of more than one year and stabilized with antidiabetic medicines such as insulin, metformin, glibenclamide, and gliclazide and diabetics with controlled diabetes as revealed by HbA1c in the range 6.2-7% were taken for the study purpose. Data were analyzed with chi square test and Fischer's exact test (when each cell frequency was less than 5) using Statistical Package for Social Sciences 17. RESULTS: Maximum (53; 73.6%) diabetics and all non-diabetics had aPTT in the range 26-40 seconds. Maximum (51; 70.8%) patients had fibrinogen beyond 351 whereas all non-diabetics had fibrinogen in the range 151-350. Mean aPTT values of the diabetic patients and non-diabetic persons were 29.88 ± 4.89 seconds and 32.44 ± 2.25 seconds respectively. Mean fibrinogen values of the diabetic patients and non-diabetic persons were 388.57 ± 60.90 mg/dL and 320.89 ± 10.20 mg/dL respectively. Test data identified in results were statistically significant for aPTT (p value 0.000) and fibrinogen (p value 0.000) between the diabetics and non-diabetics. CONCLUSIONS: Diabetics have an increased level of fibrinogen and relatively shortened aPTT as compared to the non-diabetic patients.