Acute pancreatitis(AP)is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available.One of the pharmacological targets that merits further research is the ne...Acute pancreatitis(AP)is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available.One of the pharmacological targets that merits further research is the neurokinin 1 receptor(NK1R),which is found on pancreatic acinar cells and responds to the neuropeptide substance P(SP)that participates in AP.Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development,the regulatory mechanism remains unclear.In this study,we found that following activation of NK1R by SP,b-arrestin1,a scaffold protein of NK1R,down-regulated transcription of Adss,Adsl,and Ampd in the purine nucleotide cycle,thereby inhibiting mitochondrial function through fumarate depletion.Interestingly,we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure.It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels.Our study not only provides new therapeutic strategies,leading compounds,and drug translation possibilities for AP,but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.展开更多
Root hairs(RHs)are mixed tip-and non-tip-growing protrusions derived from root epidermal cells that play essential roles in nutrient and water uptake,root anchorage,and interactions with soil microorganisms.Nutrient a...Root hairs(RHs)are mixed tip-and non-tip-growing protrusions derived from root epidermal cells that play essential roles in nutrient and water uptake,root anchorage,and interactions with soil microorganisms.Nutrient availability and temperature are critical and interconnected factors for sustained plant growth,but the molecular mechanisms that underlie their perception and downstream signaling pathways remain unclear.Here,we show that moderately low temperature(10◦C)induces a strong RH elongation response mediated by several molecular components of the auxin pathway.Specifically,auxin biosynthesis mediated by TAA1/YUCCAs,auxin transport via PIN2,PIN4,and AUX1,and auxin signaling regulated by TIR1/AFB2 in conjunction with specific ARFs(ARF6/ARF8 and ARF7,but not ARF19)contribute to the RH response under moderately low temperature.These findings establish the auxin biosynthesis and signaling pathway as a central regulatory process driving RH growth under moderate low-temperature conditions in roots.Our work underscores the importance of moderately low temperature as a stimulus that interacts with complex nutritional signaling originating from the growth medium and the plant nutritional status;this process has the potential to be fine-tuned for future biotechnological applications to enhance nutrient uptake.展开更多
Unnecessary exposure to ionizing radiation(IR)often causes acute and chronic oxidative damages to normal cells and organs,leading to serious physiological and even life-threatening consequences.Amifostine(AMF)is a val...Unnecessary exposure to ionizing radiation(IR)often causes acute and chronic oxidative damages to normal cells and organs,leading to serious physiological and even life-threatening consequences.Amifostine(AMF)is a validated radioprotectant extensively applied in radiation and chemotherapy medicine,but the short half-life limits its bioavailability and clinical applications,remaining as a great challenge to be addressed.DNAassembled nanostructures especially the tetrahedral framework nucleic acids(tFNAs)are promising nanocarriers with preeminent biosafety,low biotoxicity,and high transport efficiency.The tFNAs also have a relative long-term maintenance for structural stability and excellent endocytosis capacity.We therefore synthesized a tFNA-based delivery system of AMF for multi-organ radioprotection(tFNAs@AMF,also termed nanosuit).By establishing the mice models of accidental total body irradiation(TBI)and radiotherapy model of Lewis lung cancer,we demonstrated that the nanosuit could shield normal cells from IR-induced DNA damage by regulating the molecular biomarkers of anti-apoptosis and anti-oxidative stress.In the accidental total body irradiation(TBI)mice model,the nanosuit pretreated mice exhibited satisfactory alteration of superoxide dismutase(SOD)activities and malondialdehyde(MDA)contents,and functional recovery of hematopoietic system,reducing IRinduced pathological damages of multi-organ and safeguarding mice from lethal radiation.More importantly,the nanosuit showed a selective radioprotection of the normal organs without interferences of tumor control in the radiotherapy model of Lewis lung cancer.Based on a conveniently available DNA tetrahedron-based nanocarrier,this work presents a high-efficiency delivery system of AMF with the prolonged half-life and enhanced radioprotection for multi-organs.Such nanosuit pioneers a promising strategy with great clinical translation potential for radioactivity protection.展开更多
Biophotonics is an emerging multidisciplinary research area, embracing all light-based technologies applied to the life sciences and medicine [1-6]. The expression itself is the combination of the Greek syllables ＂b...Biophotonics is an emerging multidisciplinary research area, embracing all light-based technologies applied to the life sciences and medicine [1-6]. The expression itself is the combination of the Greek syllables ＂bios＂ standing for life and ＂phos＂ standing for light. Photonics is the technical term for all methodologies and technologies utilizing photons over the whole spectrum from X-ray over the ultraviolet, visible and the infrared to the terahertz region, and its interaction with any matter. Beyond this definition, biophotonics is a scientific discipline of remarkable societal importance. As a part of photonics, it has proved to be an important enabling technology for accelerated progress in medicine and biotechnology. It can do so, because it originated at the interface of the most innovative academic disciplines of the last century, i.e., photonics, biotechnology and nanotechnologies. This field of research brings together scientists from different professions, such as physicists, biologists, pharmacists, medical doctors, etc. To work on common projects, they need to understand the ideas and the techniques of their counterparts.展开更多
基金supported by the National Natural Science Foundation of China(No.82104598 to Chenxia Han,No.82274321 to Qing Xia,No.82170905 to Dan Du)Project of Sichuan Provincial Administration of Traditional Chinese Medicine(2023ZD04 to Qing Xia,China).
文摘Acute pancreatitis(AP)is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available.One of the pharmacological targets that merits further research is the neurokinin 1 receptor(NK1R),which is found on pancreatic acinar cells and responds to the neuropeptide substance P(SP)that participates in AP.Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development,the regulatory mechanism remains unclear.In this study,we found that following activation of NK1R by SP,b-arrestin1,a scaffold protein of NK1R,down-regulated transcription of Adss,Adsl,and Ampd in the purine nucleotide cycle,thereby inhibiting mitochondrial function through fumarate depletion.Interestingly,we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure.It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels.Our study not only provides new therapeutic strategies,leading compounds,and drug translation possibilities for AP,but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.
基金supported by grants from ANPCyT(PICT2019-0015 and PICT2021-0514)ANID-Programa Iniciativa Cientifica Milenio(ICN17_022,ICN2021_044)(C.M.)the Fondo Nacional de Desarrollo Cientifico y Tecnologico(1250304)to J.M.E.
文摘Root hairs(RHs)are mixed tip-and non-tip-growing protrusions derived from root epidermal cells that play essential roles in nutrient and water uptake,root anchorage,and interactions with soil microorganisms.Nutrient availability and temperature are critical and interconnected factors for sustained plant growth,but the molecular mechanisms that underlie their perception and downstream signaling pathways remain unclear.Here,we show that moderately low temperature(10◦C)induces a strong RH elongation response mediated by several molecular components of the auxin pathway.Specifically,auxin biosynthesis mediated by TAA1/YUCCAs,auxin transport via PIN2,PIN4,and AUX1,and auxin signaling regulated by TIR1/AFB2 in conjunction with specific ARFs(ARF6/ARF8 and ARF7,but not ARF19)contribute to the RH response under moderately low temperature.These findings establish the auxin biosynthesis and signaling pathway as a central regulatory process driving RH growth under moderate low-temperature conditions in roots.Our work underscores the importance of moderately low temperature as a stimulus that interacts with complex nutritional signaling originating from the growth medium and the plant nutritional status;this process has the potential to be fine-tuned for future biotechnological applications to enhance nutrient uptake.
基金supported by National Natural Science Foundation of China(82370929)Sichuan Science and Technology Program(2022NSFSC0002 and 2024NSFSC3508)+4 种基金Sichuan Province Youth Science and Technology Innovation Team(2022JDTD0021)Research and Develop Program,West China Hospital of Stomatology Sichuan University(RD03202302,RCDWJS2024-1)China Postdoctoral Science Foundation(GZB2023470)Sichuan Province Innovative Talent Funding Project for Postdoctoral Fellows(BX202317)The authors would like to thank Dr.Chenghui Li(Analytical&Testing Center,Sichuan University)for technical assistance in assisting with the particle size analysis.
文摘Unnecessary exposure to ionizing radiation(IR)often causes acute and chronic oxidative damages to normal cells and organs,leading to serious physiological and even life-threatening consequences.Amifostine(AMF)is a validated radioprotectant extensively applied in radiation and chemotherapy medicine,but the short half-life limits its bioavailability and clinical applications,remaining as a great challenge to be addressed.DNAassembled nanostructures especially the tetrahedral framework nucleic acids(tFNAs)are promising nanocarriers with preeminent biosafety,low biotoxicity,and high transport efficiency.The tFNAs also have a relative long-term maintenance for structural stability and excellent endocytosis capacity.We therefore synthesized a tFNA-based delivery system of AMF for multi-organ radioprotection(tFNAs@AMF,also termed nanosuit).By establishing the mice models of accidental total body irradiation(TBI)and radiotherapy model of Lewis lung cancer,we demonstrated that the nanosuit could shield normal cells from IR-induced DNA damage by regulating the molecular biomarkers of anti-apoptosis and anti-oxidative stress.In the accidental total body irradiation(TBI)mice model,the nanosuit pretreated mice exhibited satisfactory alteration of superoxide dismutase(SOD)activities and malondialdehyde(MDA)contents,and functional recovery of hematopoietic system,reducing IRinduced pathological damages of multi-organ and safeguarding mice from lethal radiation.More importantly,the nanosuit showed a selective radioprotection of the normal organs without interferences of tumor control in the radiotherapy model of Lewis lung cancer.Based on a conveniently available DNA tetrahedron-based nanocarrier,this work presents a high-efficiency delivery system of AMF with the prolonged half-life and enhanced radioprotection for multi-organs.Such nanosuit pioneers a promising strategy with great clinical translation potential for radioactivity protection.
文摘Biophotonics is an emerging multidisciplinary research area, embracing all light-based technologies applied to the life sciences and medicine [1-6]. The expression itself is the combination of the Greek syllables ＂bios＂ standing for life and ＂phos＂ standing for light. Photonics is the technical term for all methodologies and technologies utilizing photons over the whole spectrum from X-ray over the ultraviolet, visible and the infrared to the terahertz region, and its interaction with any matter. Beyond this definition, biophotonics is a scientific discipline of remarkable societal importance. As a part of photonics, it has proved to be an important enabling technology for accelerated progress in medicine and biotechnology. It can do so, because it originated at the interface of the most innovative academic disciplines of the last century, i.e., photonics, biotechnology and nanotechnologies. This field of research brings together scientists from different professions, such as physicists, biologists, pharmacists, medical doctors, etc. To work on common projects, they need to understand the ideas and the techniques of their counterparts.
