Various studies have attempted to understand HIV infection under a diverse range of stimulants including cytokine stimulation. Pro-inflammatory cytokines, such as TNF-α, have been shown to reactivate HIV latency by i...Various studies have attempted to understand HIV infection under a diverse range of stimulants including cytokine stimulation. Pro-inflammatory cytokines, such as TNF-α, have been shown to reactivate HIV latency by inducing NF-κB mediated activation of the HIV LTR (long terminal repeats) that contain κB transcriptional binding sites. Interferon-alpha (IFN-α), an anti-viral cytokine, is not well studied as an inducer of HIV activation. However, previous work from our group has shown that HIV can block IFN-α signaling in CD4+ T cells presumably to allow for further viral replication. Initially using HEK 293T cells, we moved to CD4+ T cells lines to develop a system to determine how stimulation with different cytokines impacts signaling within T cell lines. We confirmed that in our system TNF-α triggers activation of NF-κB driven reporters but not in the presence of HIV. In addition, we show that the presence of HIV blocks IFN-α signaling. Taken together, our system demonstrates that HIV by TNF-α, will continue to block IFN-α signaling preventing it from impacting HIV activation. This system can now be used to screen for cytokine based and other molecule activators that may be influenced by the presence of HIV.展开更多
Type 2 diabetes mellitus(T2DM)increases the risk of many lethal and debilitating conditions.Among them,foot ulceration due to neuropathy,vascular disease,or trauma affects the quality of life of millions in the United...Type 2 diabetes mellitus(T2DM)increases the risk of many lethal and debilitating conditions.Among them,foot ulceration due to neuropathy,vascular disease,or trauma affects the quality of life of millions in the United States and around the world.Physiological wound healing is stalled in the inflammatory phase by the chronicity of inflammation without proceeding to the resolution phase.Despite advanced treatment,diabetic foot ulcers(DFUs)are associated with a risk of amputation.Thus,there is a need for novel therapies to address chronic inflammation,decreased angiogenesis,and impaired granulation tissue formation contributing to the non-healing of DFUs.Studies have shown promising results with resolvins(Rv)and anti-inflammatory therapies that resolve inflammation and enhance tissue healing.But many of these studies have encountered difficulty in the delivery of Rv in terms of efficiency,tissue targetability,and immunogenicity.This review summarized the perspective of optimizing the therapeutic application of Rv and cytokines by pairing them with exosomes as a novel strategy for targeted tissue delivery to treat non-healing chronic DFUs.The articles discussing the T2DM disease state,current research on Rv for treating inflammation,the role of Rv in enhancing wound healing,and exosomes as a delivery vehicle were critically reviewed to find support for the proposition of using Rv and exosomes in combination for DFUs therapy.The literature reviewed suggests the beneficial role of Rv and exosomes and exosomes loaded with antiinflammatory agents as promising therapeutic agents in ulcer healing.展开更多
With the Food and Drug Administration designation in 2017 of 3,4-methylenedioxymethamphetamine(MDMA)as a breakthrough therapy in post-traumatic stress disorder and psilocybin in treatment-resistant depression,psychede...With the Food and Drug Administration designation in 2017 of 3,4-methylenedioxymethamphetamine(MDMA)as a breakthrough therapy in post-traumatic stress disorder and psilocybin in treatment-resistant depression,psychedelic drugs have continued to garner the attention of researchers and clinicians for their promise of unmatched,rapid improvement in a multitude of psychiatric conditions.Classic psychedelic drugs including psilocybin,lysergic acid diethylamide,and ayahuasca,as well as non-classic drugs such as MDMA and ketamine,are currently being investigated for a potential therapeutic role in trauma,depressive disorders,and other psychopathologies.However,psilocybin and MDMA each have a functional profile well-suited for integration with psychotherapy.The present review focuses on psilocybin and MDMA in psychedelic-assisted therapy(PAT),as these studies compose most of the literature pool.In this review,we discuss the current and future uses of psychedelic drugs,with an emphasis on the role of MDMA and psilocybin in PAT in the setting of trauma and related comorbidities on the efficacy of psychedelic drugs across multiple psychiatric disorders.The article concludes with thoughts for future research,such as incorporating wearables and standardization of symptom scales,therapy styles,and assessment of adverse drug reactions.展开更多
It is widely assumed that fetal ischemic brain injury during labor derives almost exclusively from severe, systemic hypoxemia with marked neonatal depression and acidemia. Severe asphyxia, however, is one of several c...It is widely assumed that fetal ischemic brain injury during labor derives almost exclusively from severe, systemic hypoxemia with marked neonatal depression and acidemia. Severe asphyxia, however, is one of several causes of perinatal neurological injury and may not be the most common;most neonates diagnosed with hypoxic-ischemic encephalopathy do not have evidence of severe asphyxia. Sepsis, direct brain trauma, and drug or toxin exposure account for some cases, while mechanical forces of labor and delivery that increase fetal intracranial pressure sufficiently to impair brain perfusion may also contribute. Because of bony compliance and mobile suture lines, the fetal skull changes shape and redistributes cerebrospinal fluid during labor according to constraints imposed by contractions, and bony and soft tissue elements of the birth canal as the head descends. These accommodations, including the increase in intracranial pressure, are adaptive and necessary for efficient descent of the head while safeguarding cerebral blood flow. Autonomic reflexes mediated through central receptors normally provide ample protection of the brain from the considerable pressure exerted on the skull. On occasion, those forces, which are transmitted intracranially, may overcome the various adaptive anatomical, cardiovascular, metabolic, and neurological mechanisms that maintain cerebral perfusion and oxygen availability, resulting in ischemic brain injury. Accepting the notion of a potentially adverse impact of fetal head compression suggests that avoidance of excessive uterine activity and of relentless pushing without steady progress in descent may offer protection for the fetal brain during parturition. Excessive head compression should be considered in the differential diagnosis of ischemic encephalopathy.展开更多
Microglia are the resident macrophages of the central nervous system.Microglia possess varied morphologies and functions.Under normal physiological conditions,microglia mainly exist in a resting state and constantly m...Microglia are the resident macrophages of the central nervous system.Microglia possess varied morphologies and functions.Under normal physiological conditions,microglia mainly exist in a resting state and constantly monitor their microenvironment and survey neuronal and synaptic activity.Through the C1 q,C3 and CR3"Eat Me"and CD47 and SIRPα"Don't Eat Me"complement pathways,as well as other pathways such as CX3 CR1 signaling,resting microglia regulate synaptic pruning,a process crucial for the promotion of synapse formation and the regulation of neuronal activity and synaptic plasticity.By mediating synaptic pruning,resting microglia play an important role in the regulation of experience-dependent plasticity in the barrel cortex and visual cortex after whisker removal or monocular deprivation,and also in the regulation of learning and memory,including the modulation of memory strength,forgetfulness,and memory quality.As a response to brain injury,infection or neuroinflammation,microglia become activated and increase in number.Activated microglia change to an amoeboid shape,migrate to sites of inflammation and secrete proteins such as cytokines,chemokines and reactive oxygen species.These molecules released by microglia can lead to synaptic plasticity and learning and memory deficits associated with aging,Alzheimer's disease,traumatic brain injury,HIV-associated neurocognitive disorder,and other neurological or mental disorders such as autism,depression and post-traumatic stress disorder.With a focus mainly on recently published literature,here we reviewed the studies investigating the role of resting microglia in synaptic plasticity and learning and memory,as well as how activated microglia modulate disease-related plasticity and learning and memory deficits.By summarizing the function of microglia in these processes,we aim to provide an overview of microglia regulation of synaptic plasticity and learning and memory,and to discuss the possibility of microglia manipulation as a therapeutic to ameliorate cognitive deficits associated with aging,Alzheimer's disease,traumatic brain injury,HIV-associated neurocognitive disorder,and mental disorders.展开更多
Colorectal cancer(CRC)is the third leading cause of cancer deaths worldwide and the fourth most common cancer diagnosed among men and women in the United States.Considering the risk factors of CRC,dietary therapy has ...Colorectal cancer(CRC)is the third leading cause of cancer deaths worldwide and the fourth most common cancer diagnosed among men and women in the United States.Considering the risk factors of CRC,dietary therapy has become one of the most effective approaches in reducing CRC morbidity and mortality.The use of probiotics is increasing in popularity for both the prevention and treatment of a variety of diseases.As the most common types of microbes used as probiotics,lactic acid bacteria(LAB)are comprised of an ecologically diverse group of microorganisms united by formation of lactic acid as the primary metabolite of sugar metabolism.LAB have been successfully used in managing diarrhea,food allergies,and inflammatory bowel disease.LAB also demonstrated a host of properties in preventing colorectal cancer development by inhibiting initiation or progression through multiple pathways.In this review,we discuss recent insights into cellular and molecular mechanisms of LAB in CRC prevention including apoptosis,antioxidant DNA damages,immune responses,and epigenetics.The emerging experimental findings from clinical trials as well as the proposed mechanisms of gut microbiota in carcinogenesis will also be briefly discussed.展开更多
The field of gastroenterology has recently seen a surge in wearable technology to monitor physical activity,sleep quality,pain,and even gut activity.The past decade has seen the emergence of wearable devices including...The field of gastroenterology has recently seen a surge in wearable technology to monitor physical activity,sleep quality,pain,and even gut activity.The past decade has seen the emergence of wearable devices including Fitbit,Apple Watch,AbStats,and ingestible sensors.In this review,we discuss current and future devices designed to measure sweat biomarkers,steps taken,sleep efficiency,gastric electrical activity,stomach pH,and intestinal contents.We also summarize several clinical studies to better understand wearable devices so that we may assess their potential benefit in improving healthcare while also weighing the challenges that must be addressed.展开更多
Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy r...Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced cytokines, in patients with suspected PANDAS/CANS.展开更多
A high-performance liquid chromatography-electrospray ionization tandem mass spectrometric （HPLC- ESI-MS/MS） method was developed for the quantification of MHl148-clorgyline amide （NMl-amide）, a novel tumor-target...A high-performance liquid chromatography-electrospray ionization tandem mass spectrometric （HPLC- ESI-MS/MS） method was developed for the quantification of MHl148-clorgyline amide （NMl-amide）, a novel tumor-targeting monoamine oxidase A inhibitor, in mouse plasma. The method was validated in terms of sensitivity, precision, accuracy, recovery and stability and then applied to a pharmacokinetic study of NMl-amide in mice following intravenous administration. NMl-amide together with the internal standard （IS）, MHI-148, was extracted by protein precipitation using acetonitrile. Multiple reaction monitoring was used for quantification of NMl-amide by detecting m/z transition of 491.2-361.9, and 685.3-258.2 for NMl-amide and the IS, respectively. The lower limit of quantification （LLOQ） of the HPLC- MS/MS method for NMl-amide was 0.005 μg/mL and the linear calibration curve was acquired with R2〉 0.99 in the concentration range of 0.005-2μg/mL. The intra- and inter-day precisions of the assay were assessed by percentage of the coefficient of variations, which was within 9.8% at LLOQ and 14.0% for other quality control samples, whereas the mean accuracy ranged from 86.8% to 113.2%. The samples were stable under storage and experimental conditions. This method was successfully applied to a pharmacokinetic study in mice following intravenous administration of 5 mg/kg NMl-amide.展开更多
As the population across the globe continues to dramatically increase,the prevalence of cognitive impairment and dementia will inevitably increase as well,placing increasing burden on families and health care systems....As the population across the globe continues to dramatically increase,the prevalence of cognitive impairment and dementia will inevitably increase as well,placing increasing burden on families and health care systems.Technological advancements over the past decade provide potential benefit in not only relieving caregiver burden of caring for a loved one with dementia,but also enables individuals with dementia to age in place.Technological devices have served to improve functioning,tracking and mobility.Similarly,smartphones,tablets and the ubiquitous world wide web have facilitated the dissemination of health information to previously hard to reach populations largely through use of various social media platforms.In this review,we discuss the current and future uses of technology via devices and social media to promote healthy aging in individuals with dementia,and also limitations and challenges to consider in the future.展开更多
Hepatocellular carcinoma,the most common primary liver cancer,in an immunogenic tumor with a poor prognosis because these tumors are diagnosed at late stages.Although,surgical resection,ablation,liver transplant,and l...Hepatocellular carcinoma,the most common primary liver cancer,in an immunogenic tumor with a poor prognosis because these tumors are diagnosed at late stages.Although,surgical resection,ablation,liver transplant,and locoregional therapies are available for early stages;however,there are yet no effective treatment for advanced and recurrent tumors.Immune checkpoint inhibitor therapy and adoptive cell transfer therapy has gained the popularity with some positive results because these therapies overcome anergy and systemic immune suppression.However,still there is a lack of an effective treatment and thus there is an unmet need of a novel treatment.At present,the focus of the research is on oncolytic viral therapy and combination therapy where therapies including radiotherapy,immune checkpoint therapy,adoptive cell transfer therapy,and vaccines are combined to get an additive or synergistic effect enhancing the immune response of the liver with a cytotoxic effect on tumor cells.This review discusses the recent key development,the basis of drug resistance,immune evasion,immune tolerance,the available therapies based on stage of the tumor,and the ongoing clinical trials on immune checkpoint inhibitor therapy,adoptive cell transfer therapy,oncolytic viral vaccine therapy,and combination therapy.展开更多
Purpose: The purpose of this study was to evaluate the change in corneal wavefront aberrations in young adults who have been fit with multifocal soft contact lenses for myopia progression control. Findings have been a...Purpose: The purpose of this study was to evaluate the change in corneal wavefront aberrations in young adults who have been fit with multifocal soft contact lenses for myopia progression control. Findings have been analyzed for statistical significance and clinical relevance and compared to reportedly successful Orthokeratology outcomes. Methods: The dominant eye of 40 participants (27 women, 13 men;mean age 27.3 ± 3.2 years;range 23 to 39 years) was fit with Proclear Multifocal center distance lenses (Coopervision, Pleasanton, USA) having a variety of distance powers and reading additions. Refractive errors were limited to a range of –6.00 D up to +1.00 D of sphere, and no greater than –1.00 D of cylinder. Corneal wavefront measurements were performed over 6 mm diameters with a Zeiss Atlas 9000 corneal topographer (Zeiss Meditec, Dublin, USA) prior to, and following lens fitting. Data were converted into rectangular Fourier optics terms M, J0, J45 and RMS values for each reading addition were statistically analyzed. Following evaluation of statistical significance and clinical relevance, results were compared to published data from successful Orthokeratology treatments. Results: Statistically significant changes in higher order aberrations were detected for lenses of all reading additions. Lens groups with higher Add-powers demonstrated stronger changes with increased significance. Final RMS values relating to 2nd, 3rd and 4th Zernike Orders reached clinical significance with a wavefront error of 0.10 μm, the equivalent of 0.25D. Moreover, as Add-powers increased, 3rd and 4th order aberrations likewise showed an increase. Pre-fitting astigmatism values accounted for the highest recorded aberrations and remained predominantly unchanged. Conclusion: Proclear Multifocal center-distance contact lenses were found to increase higher order wavefront aberrations in a manner dependent on their Add-power. In comparison to successful Orthokeratology outcomes, the amounts of resulting aberrations are notably different.展开更多
Purpose: Reasons for the lack of success for contact lens patients range from poor fit, to discomfort or to a less than optimum wearing schedule. This project was a preliminary investigation of customized soft toric c...Purpose: Reasons for the lack of success for contact lens patients range from poor fit, to discomfort or to a less than optimum wearing schedule. This project was a preliminary investigation of customized soft toric contact lenses as an alternative for unsuccessful contact lens patients or potential drop-outs. Methods: Fifteen healthy non-compromised, previously unsuccessful contact lens wearing patients (13 women, 2 men) with ages from 21 to 33 years (25.1 ± 2.7 years) were the subjects for this study. They were empirically fitted with 15 astigmatic and 5 spherical customized SpecialEyes soft contact lenses. Visual acuities, comfort, lens movement, and rotation were evaluated. Results: Patients fitted with customized SpecialEyes soft contact lenses had statistically significant better visual acuities than with Phoropter Manifest Refraction. The lenses used in this study centered well and moved no more than 1 mm upon each blink. Lens rotation was less than 10 degrees for all toric lenses. Patients gave very positive vision and comfort ratings. Conclusion: This preliminary study supports the application of a software program to empirically design and manufacture Special Eyes custom soft lenses based upon corneal topographical parameters and subjective manifest refraction for those patients who either have challenging corneal parameters, high sphero-cylindrical prescriptions, or are currently dissatisfied with their contact lenses and are potential drop-outs.展开更多
Background: Degraded peripheral vision has been hypothesized to be a stimulus for the development of foveal refractive error. Contact lenses have been widely used to correct central vision, but their impacts on periph...Background: Degraded peripheral vision has been hypothesized to be a stimulus for the development of foveal refractive error. Contact lenses have been widely used to correct central vision, but their impacts on peripheral vision are still unknown. The purpose of this study was to use optical model software to evaluate the peripheral optics of rigid gas permeable (RGP) and soft contact lenses (SCLs) in isolation. This will better assist us in understanding their peripheral optical performances on human eyes. Methods: An optical design software package (Zemax EE) was used to model peripheral optics of Menicon RGP lens and Acuvue 2 SCLs. Profiles of sphero-cylindrical power and major higher-order aberrations were computed in 10osteps out to 40o off-axis eccentricity for –3.0 D central focal power contact lens. The results of optical modeling were analyzed and compared with previously published experimental data. Results: –3.0 D RGP lenses and SCLs had –1.4 D and –2.0 D dioptric power at 40o eccentricity, respectively. The reduced dioptric power in the periphery of the analyzed contact lenses quantitatively matched with the reduced amount of hyperopic field curvature found from experimental data when these contact lenses fitted on human eyes. Cylindrical power increased to 0.3 D ~ 0.4 D at 40o eccentricity for both lens types. In addition, both contact lens types produced higher order aberrations, namely 1.2 μm coma and 0.15 μm spherical aberration at 40o eccentricity. Conclusions: Compared to SCLs, RGP lenses with equal focal power had less dioptric power in the periphery. Both RGP lenses and SCLs produced the same amount of major higher-order aberrations with increasing of the field angle. Some of these results can be used to predict and understand the peripheral optical performance of contact lenses on human eyes.展开更多
Under warm temperatures,plants adjust their morphologies for environmental adaption via precise gene expression regulation.However,the function and regulation of alternative polyadenylation(APA),an important fine-tuni...Under warm temperatures,plants adjust their morphologies for environmental adaption via precise gene expression regulation.However,the function and regulation of alternative polyadenylation(APA),an important fine-tuning of gene expression,remains unknown in plant thermomorphogenesis.In this study,we found that SUMOylation,a critical post-translational modification,is induced by a long-term treat-ment at warm temperatures via a SUMO ligase SIZ1 in Arabidopsis.Disruption of SIZ1 altered the global usage of polyadenylation signals and affected the APA dynamic of thermomorphogenesis-related genes.CPSF100,a key subunit of the CPSF complex for polyadenylation regulation,is SUMOylated by SIZ1.Importantly,we demonstrated that SUMOylation is essential for the function of CPSF1oo in genome-wide polyadenylation site choice during thermomorphogenesis.Further analyses revealed that the SUMO conjugation on CPSF100 attenuates its interaction with two isoforms of its partner CPSF30,increasing the nuclear accumulation of CPsF1oo for polyadenylation regulation.In summary,our study uncovers a regulatory mechanism of APA via SiZ1-mediated SUMOylation in plant thermomorpho-genesis.展开更多
目的观察糖尿病患者白细胞端粒酶活性变化,并分析外周血白细胞端粒酶活性的影响因素。方法以1型糖尿病(T1DM)患者40例为A组,2型糖尿病(T2DM)患者80例为B组,健康体检者50例为对照组。抽取各组外周静脉血5 m L,离心后提取白细胞,采用荧光...目的观察糖尿病患者白细胞端粒酶活性变化,并分析外周血白细胞端粒酶活性的影响因素。方法以1型糖尿病(T1DM)患者40例为A组,2型糖尿病(T2DM)患者80例为B组,健康体检者50例为对照组。抽取各组外周静脉血5 m L,离心后提取白细胞,采用荧光定量PCR法检测各组白细胞中端粒酶活性。采用多元线性回归分析法分析T2DM患者白细胞中端粒酶活性的影响因素。结果 A、B、C组外周血白细胞端粒酶活性(Ct值)分别为31.64±1.03、32.22±0.75、33.19±0.95,组间两两比较,P均<0.05。性别、吸烟状况与T2DM患者外周血白细胞端粒酶活性有关(P均<0.05)。结论糖尿病患者外周血白细胞端粒酶活性升高,且T1DM患者白细胞端粒酶升高更明显。性别、吸烟状况是T2DM患者外周血白细胞端粒酶活性的影响因素。展开更多
文摘Various studies have attempted to understand HIV infection under a diverse range of stimulants including cytokine stimulation. Pro-inflammatory cytokines, such as TNF-α, have been shown to reactivate HIV latency by inducing NF-κB mediated activation of the HIV LTR (long terminal repeats) that contain κB transcriptional binding sites. Interferon-alpha (IFN-α), an anti-viral cytokine, is not well studied as an inducer of HIV activation. However, previous work from our group has shown that HIV can block IFN-α signaling in CD4+ T cells presumably to allow for further viral replication. Initially using HEK 293T cells, we moved to CD4+ T cells lines to develop a system to determine how stimulation with different cytokines impacts signaling within T cell lines. We confirmed that in our system TNF-α triggers activation of NF-κB driven reporters but not in the presence of HIV. In addition, we show that the presence of HIV blocks IFN-α signaling. Taken together, our system demonstrates that HIV by TNF-α, will continue to block IFN-α signaling preventing it from impacting HIV activation. This system can now be used to screen for cytokine based and other molecule activators that may be influenced by the presence of HIV.
基金Supported by the Intramural Grant IMR Rai 12397B from the Western University of Health Sciences,Pomona,Californiathe Grants from the National Institutes of Health,United States,R01 HL144125 and R01 HL147662.
文摘Type 2 diabetes mellitus(T2DM)increases the risk of many lethal and debilitating conditions.Among them,foot ulceration due to neuropathy,vascular disease,or trauma affects the quality of life of millions in the United States and around the world.Physiological wound healing is stalled in the inflammatory phase by the chronicity of inflammation without proceeding to the resolution phase.Despite advanced treatment,diabetic foot ulcers(DFUs)are associated with a risk of amputation.Thus,there is a need for novel therapies to address chronic inflammation,decreased angiogenesis,and impaired granulation tissue formation contributing to the non-healing of DFUs.Studies have shown promising results with resolvins(Rv)and anti-inflammatory therapies that resolve inflammation and enhance tissue healing.But many of these studies have encountered difficulty in the delivery of Rv in terms of efficiency,tissue targetability,and immunogenicity.This review summarized the perspective of optimizing the therapeutic application of Rv and cytokines by pairing them with exosomes as a novel strategy for targeted tissue delivery to treat non-healing chronic DFUs.The articles discussing the T2DM disease state,current research on Rv for treating inflammation,the role of Rv in enhancing wound healing,and exosomes as a delivery vehicle were critically reviewed to find support for the proposition of using Rv and exosomes in combination for DFUs therapy.The literature reviewed suggests the beneficial role of Rv and exosomes and exosomes loaded with antiinflammatory agents as promising therapeutic agents in ulcer healing.
文摘With the Food and Drug Administration designation in 2017 of 3,4-methylenedioxymethamphetamine(MDMA)as a breakthrough therapy in post-traumatic stress disorder and psilocybin in treatment-resistant depression,psychedelic drugs have continued to garner the attention of researchers and clinicians for their promise of unmatched,rapid improvement in a multitude of psychiatric conditions.Classic psychedelic drugs including psilocybin,lysergic acid diethylamide,and ayahuasca,as well as non-classic drugs such as MDMA and ketamine,are currently being investigated for a potential therapeutic role in trauma,depressive disorders,and other psychopathologies.However,psilocybin and MDMA each have a functional profile well-suited for integration with psychotherapy.The present review focuses on psilocybin and MDMA in psychedelic-assisted therapy(PAT),as these studies compose most of the literature pool.In this review,we discuss the current and future uses of psychedelic drugs,with an emphasis on the role of MDMA and psilocybin in PAT in the setting of trauma and related comorbidities on the efficacy of psychedelic drugs across multiple psychiatric disorders.The article concludes with thoughts for future research,such as incorporating wearables and standardization of symptom scales,therapy styles,and assessment of adverse drug reactions.
文摘It is widely assumed that fetal ischemic brain injury during labor derives almost exclusively from severe, systemic hypoxemia with marked neonatal depression and acidemia. Severe asphyxia, however, is one of several causes of perinatal neurological injury and may not be the most common;most neonates diagnosed with hypoxic-ischemic encephalopathy do not have evidence of severe asphyxia. Sepsis, direct brain trauma, and drug or toxin exposure account for some cases, while mechanical forces of labor and delivery that increase fetal intracranial pressure sufficiently to impair brain perfusion may also contribute. Because of bony compliance and mobile suture lines, the fetal skull changes shape and redistributes cerebrospinal fluid during labor according to constraints imposed by contractions, and bony and soft tissue elements of the birth canal as the head descends. These accommodations, including the increase in intracranial pressure, are adaptive and necessary for efficient descent of the head while safeguarding cerebral blood flow. Autonomic reflexes mediated through central receptors normally provide ample protection of the brain from the considerable pressure exerted on the skull. On occasion, those forces, which are transmitted intracranially, may overcome the various adaptive anatomical, cardiovascular, metabolic, and neurological mechanisms that maintain cerebral perfusion and oxygen availability, resulting in ischemic brain injury. Accepting the notion of a potentially adverse impact of fetal head compression suggests that avoidance of excessive uterine activity and of relentless pushing without steady progress in descent may offer protection for the fetal brain during parturition. Excessive head compression should be considered in the differential diagnosis of ischemic encephalopathy.
文摘Microglia are the resident macrophages of the central nervous system.Microglia possess varied morphologies and functions.Under normal physiological conditions,microglia mainly exist in a resting state and constantly monitor their microenvironment and survey neuronal and synaptic activity.Through the C1 q,C3 and CR3"Eat Me"and CD47 and SIRPα"Don't Eat Me"complement pathways,as well as other pathways such as CX3 CR1 signaling,resting microglia regulate synaptic pruning,a process crucial for the promotion of synapse formation and the regulation of neuronal activity and synaptic plasticity.By mediating synaptic pruning,resting microglia play an important role in the regulation of experience-dependent plasticity in the barrel cortex and visual cortex after whisker removal or monocular deprivation,and also in the regulation of learning and memory,including the modulation of memory strength,forgetfulness,and memory quality.As a response to brain injury,infection or neuroinflammation,microglia become activated and increase in number.Activated microglia change to an amoeboid shape,migrate to sites of inflammation and secrete proteins such as cytokines,chemokines and reactive oxygen species.These molecules released by microglia can lead to synaptic plasticity and learning and memory deficits associated with aging,Alzheimer's disease,traumatic brain injury,HIV-associated neurocognitive disorder,and other neurological or mental disorders such as autism,depression and post-traumatic stress disorder.With a focus mainly on recently published literature,here we reviewed the studies investigating the role of resting microglia in synaptic plasticity and learning and memory,as well as how activated microglia modulate disease-related plasticity and learning and memory deficits.By summarizing the function of microglia in these processes,we aim to provide an overview of microglia regulation of synaptic plasticity and learning and memory,and to discuss the possibility of microglia manipulation as a therapeutic to ameliorate cognitive deficits associated with aging,Alzheimer's disease,traumatic brain injury,HIV-associated neurocognitive disorder,and mental disorders.
基金Supported by Grant No.NSFC-81272444 to Zhong LNo.PN-II-ID-PCE-2012-4-0608 Nr.48/02.09.2013 to Covasa M
文摘Colorectal cancer(CRC)is the third leading cause of cancer deaths worldwide and the fourth most common cancer diagnosed among men and women in the United States.Considering the risk factors of CRC,dietary therapy has become one of the most effective approaches in reducing CRC morbidity and mortality.The use of probiotics is increasing in popularity for both the prevention and treatment of a variety of diseases.As the most common types of microbes used as probiotics,lactic acid bacteria(LAB)are comprised of an ecologically diverse group of microorganisms united by formation of lactic acid as the primary metabolite of sugar metabolism.LAB have been successfully used in managing diarrhea,food allergies,and inflammatory bowel disease.LAB also demonstrated a host of properties in preventing colorectal cancer development by inhibiting initiation or progression through multiple pathways.In this review,we discuss recent insights into cellular and molecular mechanisms of LAB in CRC prevention including apoptosis,antioxidant DNA damages,immune responses,and epigenetics.The emerging experimental findings from clinical trials as well as the proposed mechanisms of gut microbiota in carcinogenesis will also be briefly discussed.
文摘The field of gastroenterology has recently seen a surge in wearable technology to monitor physical activity,sleep quality,pain,and even gut activity.The past decade has seen the emergence of wearable devices including Fitbit,Apple Watch,AbStats,and ingestible sensors.In this review,we discuss current and future devices designed to measure sweat biomarkers,steps taken,sleep efficiency,gastric electrical activity,stomach pH,and intestinal contents.We also summarize several clinical studies to better understand wearable devices so that we may assess their potential benefit in improving healthcare while also weighing the challenges that must be addressed.
文摘Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced cytokines, in patients with suspected PANDAS/CANS.
基金supported by USC-Taiwan Center for Translational Researchthe Daniel Tsai Family Fund+1 种基金Boyd & Elsie Welin Professorshipby the Department of Defense Prostate Cancer Research Program Grant W81XWH-12-1-0282
文摘A high-performance liquid chromatography-electrospray ionization tandem mass spectrometric （HPLC- ESI-MS/MS） method was developed for the quantification of MHl148-clorgyline amide （NMl-amide）, a novel tumor-targeting monoamine oxidase A inhibitor, in mouse plasma. The method was validated in terms of sensitivity, precision, accuracy, recovery and stability and then applied to a pharmacokinetic study of NMl-amide in mice following intravenous administration. NMl-amide together with the internal standard （IS）, MHI-148, was extracted by protein precipitation using acetonitrile. Multiple reaction monitoring was used for quantification of NMl-amide by detecting m/z transition of 491.2-361.9, and 685.3-258.2 for NMl-amide and the IS, respectively. The lower limit of quantification （LLOQ） of the HPLC- MS/MS method for NMl-amide was 0.005 μg/mL and the linear calibration curve was acquired with R2〉 0.99 in the concentration range of 0.005-2μg/mL. The intra- and inter-day precisions of the assay were assessed by percentage of the coefficient of variations, which was within 9.8% at LLOQ and 14.0% for other quality control samples, whereas the mean accuracy ranged from 86.8% to 113.2%. The samples were stable under storage and experimental conditions. This method was successfully applied to a pharmacokinetic study in mice following intravenous administration of 5 mg/kg NMl-amide.
文摘As the population across the globe continues to dramatically increase,the prevalence of cognitive impairment and dementia will inevitably increase as well,placing increasing burden on families and health care systems.Technological advancements over the past decade provide potential benefit in not only relieving caregiver burden of caring for a loved one with dementia,but also enables individuals with dementia to age in place.Technological devices have served to improve functioning,tracking and mobility.Similarly,smartphones,tablets and the ubiquitous world wide web have facilitated the dissemination of health information to previously hard to reach populations largely through use of various social media platforms.In this review,we discuss the current and future uses of technology via devices and social media to promote healthy aging in individuals with dementia,and also limitations and challenges to consider in the future.
文摘Hepatocellular carcinoma,the most common primary liver cancer,in an immunogenic tumor with a poor prognosis because these tumors are diagnosed at late stages.Although,surgical resection,ablation,liver transplant,and locoregional therapies are available for early stages;however,there are yet no effective treatment for advanced and recurrent tumors.Immune checkpoint inhibitor therapy and adoptive cell transfer therapy has gained the popularity with some positive results because these therapies overcome anergy and systemic immune suppression.However,still there is a lack of an effective treatment and thus there is an unmet need of a novel treatment.At present,the focus of the research is on oncolytic viral therapy and combination therapy where therapies including radiotherapy,immune checkpoint therapy,adoptive cell transfer therapy,and vaccines are combined to get an additive or synergistic effect enhancing the immune response of the liver with a cytotoxic effect on tumor cells.This review discusses the recent key development,the basis of drug resistance,immune evasion,immune tolerance,the available therapies based on stage of the tumor,and the ongoing clinical trials on immune checkpoint inhibitor therapy,adoptive cell transfer therapy,oncolytic viral vaccine therapy,and combination therapy.
文摘Purpose: The purpose of this study was to evaluate the change in corneal wavefront aberrations in young adults who have been fit with multifocal soft contact lenses for myopia progression control. Findings have been analyzed for statistical significance and clinical relevance and compared to reportedly successful Orthokeratology outcomes. Methods: The dominant eye of 40 participants (27 women, 13 men;mean age 27.3 ± 3.2 years;range 23 to 39 years) was fit with Proclear Multifocal center distance lenses (Coopervision, Pleasanton, USA) having a variety of distance powers and reading additions. Refractive errors were limited to a range of –6.00 D up to +1.00 D of sphere, and no greater than –1.00 D of cylinder. Corneal wavefront measurements were performed over 6 mm diameters with a Zeiss Atlas 9000 corneal topographer (Zeiss Meditec, Dublin, USA) prior to, and following lens fitting. Data were converted into rectangular Fourier optics terms M, J0, J45 and RMS values for each reading addition were statistically analyzed. Following evaluation of statistical significance and clinical relevance, results were compared to published data from successful Orthokeratology treatments. Results: Statistically significant changes in higher order aberrations were detected for lenses of all reading additions. Lens groups with higher Add-powers demonstrated stronger changes with increased significance. Final RMS values relating to 2nd, 3rd and 4th Zernike Orders reached clinical significance with a wavefront error of 0.10 μm, the equivalent of 0.25D. Moreover, as Add-powers increased, 3rd and 4th order aberrations likewise showed an increase. Pre-fitting astigmatism values accounted for the highest recorded aberrations and remained predominantly unchanged. Conclusion: Proclear Multifocal center-distance contact lenses were found to increase higher order wavefront aberrations in a manner dependent on their Add-power. In comparison to successful Orthokeratology outcomes, the amounts of resulting aberrations are notably different.
文摘Purpose: Reasons for the lack of success for contact lens patients range from poor fit, to discomfort or to a less than optimum wearing schedule. This project was a preliminary investigation of customized soft toric contact lenses as an alternative for unsuccessful contact lens patients or potential drop-outs. Methods: Fifteen healthy non-compromised, previously unsuccessful contact lens wearing patients (13 women, 2 men) with ages from 21 to 33 years (25.1 ± 2.7 years) were the subjects for this study. They were empirically fitted with 15 astigmatic and 5 spherical customized SpecialEyes soft contact lenses. Visual acuities, comfort, lens movement, and rotation were evaluated. Results: Patients fitted with customized SpecialEyes soft contact lenses had statistically significant better visual acuities than with Phoropter Manifest Refraction. The lenses used in this study centered well and moved no more than 1 mm upon each blink. Lens rotation was less than 10 degrees for all toric lenses. Patients gave very positive vision and comfort ratings. Conclusion: This preliminary study supports the application of a software program to empirically design and manufacture Special Eyes custom soft lenses based upon corneal topographical parameters and subjective manifest refraction for those patients who either have challenging corneal parameters, high sphero-cylindrical prescriptions, or are currently dissatisfied with their contact lenses and are potential drop-outs.
文摘Background: Degraded peripheral vision has been hypothesized to be a stimulus for the development of foveal refractive error. Contact lenses have been widely used to correct central vision, but their impacts on peripheral vision are still unknown. The purpose of this study was to use optical model software to evaluate the peripheral optics of rigid gas permeable (RGP) and soft contact lenses (SCLs) in isolation. This will better assist us in understanding their peripheral optical performances on human eyes. Methods: An optical design software package (Zemax EE) was used to model peripheral optics of Menicon RGP lens and Acuvue 2 SCLs. Profiles of sphero-cylindrical power and major higher-order aberrations were computed in 10osteps out to 40o off-axis eccentricity for –3.0 D central focal power contact lens. The results of optical modeling were analyzed and compared with previously published experimental data. Results: –3.0 D RGP lenses and SCLs had –1.4 D and –2.0 D dioptric power at 40o eccentricity, respectively. The reduced dioptric power in the periphery of the analyzed contact lenses quantitatively matched with the reduced amount of hyperopic field curvature found from experimental data when these contact lenses fitted on human eyes. Cylindrical power increased to 0.3 D ~ 0.4 D at 40o eccentricity for both lens types. In addition, both contact lens types produced higher order aberrations, namely 1.2 μm coma and 0.15 μm spherical aberration at 40o eccentricity. Conclusions: Compared to SCLs, RGP lenses with equal focal power had less dioptric power in the periphery. Both RGP lenses and SCLs produced the same amount of major higher-order aberrations with increasing of the field angle. Some of these results can be used to predict and understand the peripheral optical performance of contact lenses on human eyes.
基金supported by grants from the Major Program of Guangdong Basic and Applied Research(2019B030302006)the National Natural Science Foundation of China(32000449,32270292,32270344,32270752,and 32170593)+3 种基金the China Postdoctoral Science Foundation(2020M672674)the Program for Changjang Scholars,the Natural Science Foundation of Guangdong Province,China(2024A1515011497,2020B1515020007,and 2024A1515011071)the Guangdong Provincial Pearl River Talent Plan(2019QN01N108)the National Science Foundation of USA(2347540).
文摘Under warm temperatures,plants adjust their morphologies for environmental adaption via precise gene expression regulation.However,the function and regulation of alternative polyadenylation(APA),an important fine-tuning of gene expression,remains unknown in plant thermomorphogenesis.In this study,we found that SUMOylation,a critical post-translational modification,is induced by a long-term treat-ment at warm temperatures via a SUMO ligase SIZ1 in Arabidopsis.Disruption of SIZ1 altered the global usage of polyadenylation signals and affected the APA dynamic of thermomorphogenesis-related genes.CPSF100,a key subunit of the CPSF complex for polyadenylation regulation,is SUMOylated by SIZ1.Importantly,we demonstrated that SUMOylation is essential for the function of CPSF1oo in genome-wide polyadenylation site choice during thermomorphogenesis.Further analyses revealed that the SUMO conjugation on CPSF100 attenuates its interaction with two isoforms of its partner CPSF30,increasing the nuclear accumulation of CPsF1oo for polyadenylation regulation.In summary,our study uncovers a regulatory mechanism of APA via SiZ1-mediated SUMOylation in plant thermomorpho-genesis.
文摘目的观察糖尿病患者白细胞端粒酶活性变化,并分析外周血白细胞端粒酶活性的影响因素。方法以1型糖尿病(T1DM)患者40例为A组,2型糖尿病(T2DM)患者80例为B组,健康体检者50例为对照组。抽取各组外周静脉血5 m L,离心后提取白细胞,采用荧光定量PCR法检测各组白细胞中端粒酶活性。采用多元线性回归分析法分析T2DM患者白细胞中端粒酶活性的影响因素。结果 A、B、C组外周血白细胞端粒酶活性(Ct值)分别为31.64±1.03、32.22±0.75、33.19±0.95,组间两两比较,P均<0.05。性别、吸烟状况与T2DM患者外周血白细胞端粒酶活性有关(P均<0.05)。结论糖尿病患者外周血白细胞端粒酶活性升高,且T1DM患者白细胞端粒酶升高更明显。性别、吸烟状况是T2DM患者外周血白细胞端粒酶活性的影响因素。
