The etiology of most cases of idiopathic bile acid malabsorption （IBAH） is unknown. In this study, a Swedish family with bile acid malabsorption in three consecutive generations was screened for mutations in the ile...The etiology of most cases of idiopathic bile acid malabsorption （IBAH） is unknown. In this study, a Swedish family with bile acid malabsorption in three consecutive generations was screened for mutations in the ileal apical sodium-bile acid cotransporter gene （ASBT; gene symbol, SLC10A2） and in the genes for several of the nuclear receptors known to be important for ASBT expression： the farnesoid X receptor （FXR） and peroxisome proliferator activated receptor alpha （PPARα）. The patients presented with a clinical history of idiopathic chronic watery diarrhea, which was responsive to cholestyramine treatment and consistent with IBAH. Bile acid absorption was determined using ^75Se-homocholic acid taurine （SeHCAT）; bile acid synthesis was estimated by measuring the plasma levels of 7α-hydroxy-4-cholesten-3-one （C4）. The ASBT, FXR, and PPARα genes in the affected and unaffected family members were analyzed using single stranded conformation polymorphism （SSCP）, denaturing HPLC, and direct sequencing. No ASBT mutations were identified and the ASBT gene did not segregate with the bile acid malabsorption phenotype. Similarly, no mutations or polymorphisms were identified in the FXR or PPARα genes associated with the bile acid malabsorption phenotype. These studies indicate that the intestinal bile acid malabsorption in these patients cannot be attributed to defects in ASBT. In the absence of apparent ileal disease, alternative explanations such as accelerated transit through the small intestine may be responsible for the IBAM.展开更多
目的建立乳酸-羟基乙酸共聚物(25:75)(PLGA)相对分子质量(Mr)及其分布的测定方法。方法采用TSK gel G3000HHR色谱柱,以四氢呋喃为流动相,流速1.0mL/min,柱温40℃,示差折光检测器。结果凝胶排阻色谱法测定PLGA Mr及其分布系数,有良好的...目的建立乳酸-羟基乙酸共聚物(25:75)(PLGA)相对分子质量(Mr)及其分布的测定方法。方法采用TSK gel G3000HHR色谱柱,以四氢呋喃为流动相,流速1.0mL/min,柱温40℃,示差折光检测器。结果凝胶排阻色谱法测定PLGA Mr及其分布系数,有良好的线性、准确性及重复性。结论此法简便快速,结果准确,重复性好,可作为PLGA Mr及其分布的测定方法。展开更多
SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic.As part of the innate immune response to viral infe...SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic.As part of the innate immune response to viral infection, type Ⅰ interferons(IFN-Ⅰ) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes(ISGs), that collectively foster an antiviral state.We report here the identification of a group of type Ⅰ interferon suppressed genes,including fatty acid synthase(FASN), which are involved in lipid metabolism.Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection.More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern.Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type Ⅰ interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.展开更多
基金Supported by grants from the Swedish Research Council, the Karolinska Institutet and the Swedish Society of Medicine (to CE) and National Institutes of Health grants DK-47987 (to PAD)
文摘The etiology of most cases of idiopathic bile acid malabsorption （IBAH） is unknown. In this study, a Swedish family with bile acid malabsorption in three consecutive generations was screened for mutations in the ileal apical sodium-bile acid cotransporter gene （ASBT; gene symbol, SLC10A2） and in the genes for several of the nuclear receptors known to be important for ASBT expression： the farnesoid X receptor （FXR） and peroxisome proliferator activated receptor alpha （PPARα）. The patients presented with a clinical history of idiopathic chronic watery diarrhea, which was responsive to cholestyramine treatment and consistent with IBAH. Bile acid absorption was determined using ^75Se-homocholic acid taurine （SeHCAT）; bile acid synthesis was estimated by measuring the plasma levels of 7α-hydroxy-4-cholesten-3-one （C4）. The ASBT, FXR, and PPARα genes in the affected and unaffected family members were analyzed using single stranded conformation polymorphism （SSCP）, denaturing HPLC, and direct sequencing. No ASBT mutations were identified and the ASBT gene did not segregate with the bile acid malabsorption phenotype. Similarly, no mutations or polymorphisms were identified in the FXR or PPARα genes associated with the bile acid malabsorption phenotype. These studies indicate that the intestinal bile acid malabsorption in these patients cannot be attributed to defects in ASBT. In the absence of apparent ileal disease, alternative explanations such as accelerated transit through the small intestine may be responsible for the IBAM.
文摘目的建立乳酸-羟基乙酸共聚物(25:75)(PLGA)相对分子质量(Mr)及其分布的测定方法。方法采用TSK gel G3000HHR色谱柱,以四氢呋喃为流动相,流速1.0mL/min,柱温40℃,示差折光检测器。结果凝胶排阻色谱法测定PLGA Mr及其分布系数,有良好的线性、准确性及重复性。结论此法简便快速,结果准确,重复性好,可作为PLGA Mr及其分布的测定方法。
基金supported by the Research Funds from US National Institute of Health funds (AI069120, AI158154, and AI149718)the UCLA AIDS Institute and UCLA David Geffen School of Medicine-Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Award ProgramTumor Immunology Training Grant (T32CA912036A1, USA)
文摘SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic.As part of the innate immune response to viral infection, type Ⅰ interferons(IFN-Ⅰ) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes(ISGs), that collectively foster an antiviral state.We report here the identification of a group of type Ⅰ interferon suppressed genes,including fatty acid synthase(FASN), which are involved in lipid metabolism.Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection.More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern.Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type Ⅰ interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.
