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The process of wound healing is a complex, multi-phase phenomenon crucial for optimal tissue regeneration. Traditional drug delivery systems often target specific phases of wound repair, neglecting the dynamic interplay among the stages. This limitation highlights the need for comprehensive delivery systems that cater to the holistic needs of wound healing, enhancing tissue regeneration efficiency. Herein, we explored the utility of platelet-derived extracellular vesicles (pEVs) as carriers for the phototherapeutic diferuloylmethane (DIF), resulting in a formulation termed DIF@pEVs, which is designed to sequentially address the distinct phases of wound healing. Initially, upon exposure to light, administered DIF@pEVs generate photodynamic therapy-derived reactive oxygen species during the early inflammatory phase. This generation of ROS aims to modulate the inflammatory response, induce the protective mechanisms of heat shock proteins, and kickstart the tissue regeneration process. Following this initial phase, the remaining DIF and pEVs persist in promoting tissue repair and regeneration. Ultimately, it reduces inflammation, speeds up the healing process, and promotes vascular and follicular formation in a model of burn wound skin damage, thereby supporting skin regeneration. The deployment of DIF@pEVs represents an advancement in regenerative medicine, providing a precise, versatile approach to fostering regeneration across a wide range of clinical scenarios.
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Thrombotic cardiovascular diseases are a prevalent factor contributing to both physical impairment and mortality. Thrombolysis and ischemic mitigation have emerged as leading contemporary therapeutic approaches for addressing the consequences of ischemic injury and reperfusion damage. Herein, an innovative cellular-cloaked spermatozoon-driven microcellular submarine (SPCS), comprised of multimodal motifs, was designed to integrate nano-assembly thrombolytics with an immunomodulatory ability derived from innate magnetic hyperthermia. Rheotaxis-based navigation was utilized to home to and cross the clot barrier, and finally accumulate in ischemic vascular organs, where the thrombolytic motif was "switched-on" by the action of thrombus magnetic red blood cell-driven magnetic hyperthermia. In a murine model, the SPCS system combining innate magnetic hyperthermia demonstrated the capacity to augment delivery efficacy, produce nanotherapeutic outcomes, exhibit potent thrombolytic activity, and ameliorate ischemic tissue damage. These findings underscore the multifaceted potential of our designed approach, offering both thrombolytic and ischemia-mitigating effects. Given its extended therapeutic effects and thrombus-targeting capability, this biocompatible SPCS system holds promise as an innovative therapeutic agent for enhancing efficacy and preventing risks after managing thrombosis.
Subject(s)
Ischemia , Spermatozoa , Thrombosis , Animals , Male , Mice , Ischemia/therapy , Spermatozoa/drug effects , Thrombosis/drug therapy , Thrombolytic Therapy/methods , Hyperthermia, Induced/methods , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/therapeutic use , Fibrinolytic Agents/chemistry , Humans , Mice, Inbred C57BLABSTRACT
Background and Objectives: The efficacy of tranexamic acid (TXA) in reducing perioperative blood loss during total knee arthroplasty (TKA) is well established. However, the potential synergistic blood-conservation effect of topical fibrin sealant (Tisseel@) remains unclear. This study aims to assess the effectiveness of the combination of Tisseel and TXA during TKA. Materials and Methods: A single-blinded, prospective, randomized controlled trial was conducted with 100 patients (100 knees) undergoing primary TKA. Participants were randomly assigned to either the TXA group (n = 50), receiving intravenous (IV) TXA, or the Tisseel@ + TXA group (n = 50), receiving intra-articular Tisseel@ combined with IV TXA. The primary outcomes included blood transfusion rate, decrease in Hb level, calculated blood loss, and estimated total postoperative blood loss. Secondary outcomes involved assessing clinical differences between the groups. Results: The transfusion rate was zero in both groups. The average estimated blood loss in the Tisseel@ + TXA group was 0.463 ± 0.2422 L, which was similar to that of the TXA group at 0.455 ± 0.2522 L. The total calculated blood loss in the Tisseel@ + TXA group was 0.259 ± 0.1 L, compared with the TXA group's 0.268 ± 0.108 L. The mean hemoglobin reduction in the first 24 h postoperatively was 1.57 ± 0.83 g/dL for the Tisseel@ + TXA group and 1.46 ± 0.82 g/dL for the TXA-only group. The reduction in blood loss in the topical Tisseel@ + TXA group was not significantly different from that achieved in the TXA-only group. The clinical results of TKA up to the 6-week follow-up were comparable between the groups. Conclusions: The combination of the topical fibrin sealant Tisseel@ and perioperative IV TXA administration, following the described protocol, demonstrated no significant synergistic blood-conservation effect in patients undergoing TKR.
Subject(s)
Antifibrinolytic Agents , Arthroplasty, Replacement, Knee , Tranexamic Acid , Humans , Tranexamic Acid/pharmacology , Tranexamic Acid/therapeutic use , Fibrin Tissue Adhesive/pharmacology , Fibrin Tissue Adhesive/therapeutic use , Antifibrinolytic Agents/pharmacology , Antifibrinolytic Agents/therapeutic use , Arthroplasty, Replacement, Knee/adverse effects , Prospective Studies , Blood Loss, Surgical/prevention & controlABSTRACT
BACKGROUND: This study investigated the use of ultrasound-guided extracorporeal shock wave lithotripsy (ESWL) to break stones in the genitourinary tract and prevent genitourinary injury. Our goals were to achieve accurate focusing and minimal X-ray exposure for the benefit of the patients. METHODS: The LiteMed LM-9200 lithotripter with ultrasonography and fluoroscopy was used for two different procedures: autoaimed and autoperiodical. These procedures enabled dual focusing on stone localization and tracking. RESULTS: Out of 108 patients who underwent autoperiodical procedures, 29 had no gross hematuria. Among the 335 patients who received autoaimed procedures, 194 had no gross hematuria. The average duration of X-ray exposure during autoperiodical and autoaimed procedures was 120 and 50â s, respectively. CONCLUSION: The ultrasound-guided ESWL with minimal X-ray exposure was found to be useful in treating genitourinary upper-tract urolithiasis in the autoaimed procedure. Patients who underwent the autoaimed procedure experienced less gross hematuria compared to those who underwent the autoperiodical procedure.
Subject(s)
Lithotripsy , Urolithiasis , Humans , Hematuria/etiology , X-Rays , Taiwan/epidemiology , Urolithiasis/diagnostic imaging , Urolithiasis/therapy , Urolithiasis/etiology , Lithotripsy/adverse effects , Lithotripsy/methods , Ultrasonography , Ultrasonography, InterventionalABSTRACT
The combination of mirror therapy (MT) and neuromuscular electrical stimulation (NMES) has been devised as an intervention method in stroke rehabilitation; however, few studies have investigated its efficacy in lower extremity motor function recovery. In this systematic review and meta-analysis, we examined the effectiveness of combined MT and NMES therapy in improving poststroke walking speed, spasticity, balance and other gait parameters. Randomized controlled trials (RCTs) were selected from PubMed, Cochrane Library, EMBASE, and Scopus databases. In total, six RCTs which involving 181 participants were included. Our findings indicate that MT combined with NMES elicits greater improvement relative to control group in walking speed (SMD = 0.67, 95% confidence interval [CI] 0.26-1.07, P = 0.001), Berg Balance Scale (SMD = 0.72; 95% CI 0.31-1.13; P = 0.0007), cadence (SMD = 0.59, 95% CI 0.02-1.16, P = 0.04), step length (SMD = 0.94, 95% CI 0.35-1.53, P = 0.002), and stride length (SMD = 0.95, 95% CI 0.36-1.54, P = 0.002) but not in modified Ashworth scale (SMD = - 0.40, 95% CI - 1.05 to 0.26, P = 0.23). Our findings suggest that MT combined with NMES may be a suitable supplemental intervention to conventional therapy in stroke survivors.
Subject(s)
Electric Stimulation Therapy , Stroke Rehabilitation , Stroke , Humans , Mirror Movement Therapy , Recovery of Function , Stroke Rehabilitation/methods , Stroke/therapy , Electric Stimulation Therapy/methods , Lower Extremity , Electric StimulationABSTRACT
Due to their non-toxic function in biological systems, Iron oxide NPs (IO-NPs) are very attractive in biomedical applications. The magnetic properties of IO-NPs enable a variety of biomedical applications. We evaluated the usage of IO-NPs for anticancer effects. This paper lists the applications of IO-NPs in general and the clinical targeting of IO-NPs. The application of IONPs along with photothermal therapy (PTT), photodynamic therapy (PDT), and magnetic hyperthermia therapy (MHT) is highlighted in this review's explanation for cancer treatment strategies. The review's study shows that IO-NPs play a beneficial role in biological activity because of their biocompatibility, biodegradability, simplicity of production, and hybrid NPs forms with IO-NPs. In this review, we have briefly discussed cancer therapy and hyperthermia and NPs used in PTT, PDT, and MHT. IO-NPs have a particular effect on cancer therapy when combined with PTT, PDT, and MHT were the key topics of the review and were covered in depth. The IO-NPs formulations may be uniquely specialized in cancer treatments with PTT, PDT, and MHT, according to this review investigation.
Subject(s)
Hyperthermia, Induced , Nanoparticles , Neoplasms , Photochemotherapy , Ferric Compounds , Magnetic Phenomena , Neoplasms/drug therapyABSTRACT
Thrombotic vascular disorders, specifically thromboembolisms, have a significant detrimental effect on public health. Despite the numerous thrombolytic and antithrombotic drugs available, their efficacy in penetrating thrombus formations is limited, and they carry a high risk of promoting bleeding. Consequently, the current medication dosage protocols are inadequate for preventing thrombus formation, and higher doses are necessary to achieve sufficient prevention. By integrating phototherapy with antithrombotic therapy, this study addresses difficulties related to thrombus-targeted drug delivery. We developed self-assembling nanoparticles (NPs) through the optimization of a co-assembly engineering process. These NPs, called DIP-FU-PPy NPs, consist of polypyrrole (PPy), dipyridamole (DIP), and P-selectin-targeted fucoidan (FU) and are designed to be delivered directly to thrombi. DIP-FU-PPy NPs are proposed to offer various potentials, encompassing drug-loading capability, targeted accumulation in thrombus sites, near-infrared (NIR) photothermal-enhanced thrombus management with therapeutic efficacy, and prevention of rethrombosis. As predicted, DIP-FU-PPy NPs prevented thrombus recurrence and emitted visible fluorescence signals during thrombus clot penetration with no adverse effects. Our co-delivery nano-platform is a simple and versatile solution for NIR-phototherapeutic multimodal thrombus control.
Subject(s)
Nanoparticles , Thrombosis , Dipyridamole/pharmacology , Nanoparticles/therapeutic use , P-Selectin , Phototherapy/methods , Polymers , Pyrroles , Thrombosis/drug therapy , AnimalsABSTRACT
Traditional thrombolytic therapeutics for vascular blockage are affected by their limited penetration into thrombi, associated off-target side effects, and low bioavailability, leading to insufficient thrombolytic efficacy. It is hypothesized that these limitations can be overcome by the precisely controlled and targeted delivery of thrombolytic therapeutics. A theranostic platform is developed that is biocompatible, fluorescent, magnetic, and well-characterized, with multiple targeting modes. This multimodal theranostic system can be remotely visualized and magnetically guided toward thrombi, noninvasively irradiated by near-infrared (NIR) phototherapies, and remotely activated by actuated magnets for additional mechanical therapy. Magnetic guidance can also improve the penetration of nanomedicines into thrombi. In a mouse model of thrombosis, the thrombosis residues are reduced by ≈80% and with no risk of side effects or of secondary embolization. This strategy not only enables the progression of thrombolysis but also accelerates the lysis rate, thereby facilitating its prospective use in time-critical thrombolytic treatment.
Subject(s)
Thrombolytic Therapy , Thrombosis , Mice , Animals , Precision Medicine , Fibrinolytic Agents/chemistry , Fibrinolytic Agents/therapeutic use , Thrombosis/diagnostic imaging , Thrombosis/drug therapy , Magnetic PhenomenaABSTRACT
Due to the mortality associated with thrombosis and its high recurrence rate, there is a need to investigate antithrombotic approaches. Noninvasive site-specific thrombolysis is a current approach being used; however, its usage is characterized by the following limitations: low targeting efficiency, poor ability to penetrate clots, rapid half-life, lack of vascular restoration mechanisms, and risk of thrombus recurrence that is comparable to that of traditional pharmacological thrombolysis agents. Therefore, it is vital to develop an alternative technique that can overcome the aforementioned limitations. To this end, a cotton-ball-shaped platelet (PLT)-mimetic self-assembly framework engineered with a phototherapeutic poly(3,4-ethylenedioxythiophene) (PEDOT) platform has been developed. This platform is capable of delivering a synthetic peptide derived from hirudin P6 (P6) to thrombus lesions, forming P6@PEDOT@PLT nanomotors for noninvasive site-specific thrombolysis, effective anticoagulation, and vascular restoration. Regulated by P-selectin mediation, the P6@PEDOT@PLT nanomotors target the thrombus site and subsequently rupture under near-infrared (NIR) irradiation, achieving desirable sequential drug delivery. Furthermore, the movement ability of the P6@PEDOT@PLT nanomotors under NIR irradiation enables effective penetration deep into thrombus lesions, enhancing bioavailability. Biodistribution analyses have shown that the administered P6@PEDOT@PLT nanomotors exhibit extended circulation time and metabolic capabilities. In addition, the photothermal therapy/photoelectric therapy combination can significantly augment the effectiveness (ca. 72%) of thrombolysis. Consequently, the precisely delivered drug and the resultant phototherapeutic-driven heat-shock protein, immunomodulatory, anti-inflammatory, and inhibitory plasminogen activator inhibitor-1 (PAI-1) activities can restore vessels and effectively prevent rethrombosis. The described biomimetic P6@PEDOT@PLT nanomotors represent a promising option for improving the efficacy of antithrombotic therapy in thrombus-related illnesses.
Subject(s)
Thrombosis , Tissue Plasminogen Activator , Humans , Tissue Plasminogen Activator/pharmacology , Biomimetics , Tissue Distribution , Thrombosis/drug therapy , Thrombolytic Therapy/methodsABSTRACT
Mental simulation practices, such as motor imagery, action observation, and guided imagery, have been an intervention of interest in neurological and musculoskeletal rehabilitation. Application of such practices to postoperative patients in orthopedics, particularly after total knee arthroplasty, has resulted in favorable physical function outcomes. In this systematic review and meta-analysis, we wish to determine the effectiveness of mental simulation practices with standard physical therapy compared to standard physical therapy alone in patients who underwent total knee arthroplasty in terms of postoperative pain, physical functions, and patient-reported outcome measures. We identified randomized controlled trials from inception to August 28, 2021, by using the PubMed, Cochrane Library, EMBASE, and Scopus databases. Data collection was completed on August 28, 2021. Finally, eight articles (249 patients) published between 2014 and 2020 were included. The meta-analysis revealed that mental simulation practices caused more favorable results in pain [standardized mean difference = -0.42, 95% confidence interval (CI) (-0.80 to -0.04), P = 0.03], range of motion [0.55, 95% CI (0.06-1.04), P = 0.03], maximal strength of quadriceps [1.21, 95% CI (0.31-2.12), P = 0.009], and 36-Item Short-Form Survey [0.53, 95% CI (0.14-0.92), P = 0.007]. Our data suggest that mental simulation practices may be considered adjunctive to standard physiotherapy after total knee arthroplasty in patients with knee osteoarthritis.
Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Arthroplasty, Replacement, Knee/adverse effects , Humans , Physical Therapy Modalities , Randomized Controlled Trials as Topic , Range of Motion, ArticularABSTRACT
BACKGROUND: To assess clinical and functional outcomes of patients aged 40 years or older receiving PCL reconstruction surgery. METHODS: All patients older than 40 years with isolated PCL rupture who underwent PCL reconstruction surgery were enrolled into the retrospective study. Associated meniscal injuries, osteochondral lesions, postoperative complications, and the rate of return to the preinjury level of activity were extracted. Outcomes included International Knee Documentation Committee (IKDC) subjective score, Lysholm score, and Tegner activity score. The minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) were used to evaluate the clinically relevant value of PCL reconstruction in this population. RESULTS: In total, 41 patients with a mean age of 51.7 years were included. The mean follow-up time was 32.8 months. Associated lesions included meniscal injuries (48.8%) and osteochondral lesions (97.6%). Improvement in the IKDC score (from 46.5 preoperatively to 79.0 postoperatively, p < 0.0001), Lysholm score (from 65.5 to 88.3, p < 0.0001), and Tegner activity score (from 2.3 to 4.0, p < 0.0001) was recorded. The clinically relevant value based on the MCID showed that 34 of 41 patients (82.9%) had a ΔIKDC score exceeding 16.8; all patients (100%) showed a ΔLysholm score exceeding 8.9; and 35 of 41 patients (85.4%) showed a ΔTegner activity score exceeding 0.5. Regarding the PASS, none of the patients had an IKDC score exceeding 75.9 preoperatively, whereas 27 of 41 patients (65.9%) had a score of more than 75.9 postoperatively. All patient had ≥ grade II knee instability preoperatively. Postoperatively, 36 patients (87.8%) had no significant joint translation, and 5 patients (12.2%) had grade I instability. Twenty-one patients (51.2%) returned to their preinjury level of activity. Five patients (12.2%) developed Ahlbäck grade I radiographic osteoarthritis. No rerupture or other major perioperative complications were reported. CONCLUSIONS: PCL reconstruction is a reliable surgery for middle-aged patients suffering from persistent instability even after failed conservative treatment, with significant improvement in patient-reported outcomes that exceeded MCID in the majority of patients, restoration of subjective instability, and approximately half of the patients returned to preinjury activity levels. LEVEL OF EVIDENCE: Level IV, therapeutic case series.
Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Joint Instability , Posterior Cruciate Ligament Reconstruction , Posterior Cruciate Ligament , Adult , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Reconstruction/adverse effects , Follow-Up Studies , Humans , Joint Instability/surgery , Knee Joint/surgery , Middle Aged , Posterior Cruciate Ligament/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
Rapid, accessible, and highly accurate biosensors for the detection of addictive and abused drugs are needed to reduce the adverse personal and societal impacts of addiction. Modern sensors that utilize next-generation technologies, e.g., nanobiotechnology and nanoarchitectonics, have triggered revolutionary progress in the field as they allow accurate detection and tracking of trace levels of major classes of drugs. This paper reviews advances in the field of biosensors for the detection of commonly abused drugs, both prescribed such as codeine and morphine, and illegal narcotics like cocaine.
Subject(s)
Biosensing Techniques , Cocaine , Illicit Drugs , MorphineABSTRACT
Nootkatone is one of the major active ingredients of Alpiniae oxyphyllae, which has been used as both food and medicinal plants for the treatment of diarrhea, ulceration, and enuresis. In this study, we aimed to investigate whether nootkatone treatment ameliorated the progression of chronic kidney diseases (CKD) and clarified its underlying mechanisms in an obstructive nephropathy (unilateral ureteral obstructive; UUO) mouse model. Our results revealed that nootkatone treatment preventively decreased the pathological changes and significantly mitigated the collagen deposition as well as the protein expression of fibrotic markers. Nootkatone could also alleviate oxidative stress-induced injury, inflammatory cell infiltration, and renal cell apoptotic death in the kidneys of UUO mice. These results demonstrated for the first time that nootkatone protected against the progression of CKD in a UUO mouse model. It may serve as a potential therapeutic candidate for CKD intervention.
Subject(s)
Apoptosis/drug effects , Inflammation/drug therapy , Polycyclic Sesquiterpenes/pharmacology , Renal Insufficiency, Chronic/drug therapy , Alpinia/chemistry , Animals , Disease Models, Animal , Fibrosis/drug therapy , Fibrosis/metabolism , Inflammation/metabolism , Kidney/metabolism , Kidney/pathology , Male , Mice , Mice, Inbred C57BL , Oxidative Stress/drug effects , Renal Insufficiency, Chronic/metabolismABSTRACT
BACKGROUND: Despite its widespread use, the use of prostate-specific antigen (PSA) alone as a screening biomarker for prostate cancer (PCa) leads often to unwarranted prostate biopsy, over-diagnosis, and consequently, over-treatment, because of its limited specificity. There are reports that the apoptosis inhibitor of macrophage (AIM), secreted mainly by macrophages and epithelial cells, is upregulated during inflammation and facilitates immune recognition of cancerous cells by blocking human regulator of complement activation. OBJECTIVE: These controversies around the PSA utility necessitate a reexamination of its use as a screening tool. More so, despite the suggested implication of AIM in anticancer immunosurveillance, there is a dearth of information on its role in therapy response, disease progression, and clinical outcomes of patients with PCa. These inform the present study to probe the nature and role of AIM/PSA signaling in anticancer immunity and prognosis in PCa. METHODS: A combination of bioinformatics-aided statistical analyses, gene function annotation, and immune infiltrate analyses, coupled with tissue staining, and function assays, namely migration, invasion, and clonogenicity assays, we employed. RESULTS: We demonstrated that AIM and PSA expression levels are inversely correlated in PCa clinical samples and cell lines, with AIMlowPSAhigh defining PCa, compared to AIMhighPSAlow in normal samples. Concomitant aberrant PSA and significantly suppressed AIM expression levels positively correlated with high-grade disease and characterized by advanced stage prostate cancer, regardless of mutation status. We found that a high PSA/AIM ratio is associated with disease recurrence in patients with prostate cancer but is equivocal for overall survival. In addition, PSA-associated AIM suppression is implicated in the enhanced 'metastability' of PCa and a high AIM/PSA ratio is associated with strong castration-induced regression. CRISPR-mediated AIM knockout was associated with higher PSA expression while ectopic expression of AIM significantly attenuated the migration and invasive capability of PC3 and DU145 cells. Interestingly, compared to normal samples, we observed that AIM, biomarkers of T-cell activation and M1 phenotype markers are co-suppressed in PCa samples. CONCLUSION: Herein, we demonstrate that AIM/CD5L binds to PSA and that a high PSA/AIM ratio defines advanced stage PCa (regardless of mutation status), is implicated in enhanced metastability, and associated with disease recurrence, while a high AIM/PSA ratio is associated with strong castration-induced regression. More so, the ectopic expression of AIM significantly enhances the anticancer effect of Pembrolizumab and elicits an increased CD8+ T-cell count in AIMhiPSAloPDL1+ PCa cases that are respondent to Pembrolizumab treatment.
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IMPORTANCE: Passive surveillance systems are susceptible to the under-reporting of adverse events (AE) and a lack of information pertaining to vaccinated populations. Conventional active surveillance focuses on predefined AEs. Advanced data mining tools could be used to identify unusual clusters of potential AEs after vaccination. OBJECTIVE: To assess the feasibility of a novel tree-based statistical approach to the identification of AE clustering following the implementation of a varicella vaccination program among one-year-olds. SETTING AND PARTICIPANTS: This nationwide safety surveillance was based on data from the Taiwan National Health Insurance database and National Immunization Information System for the period 2004 through 2014. The study population was children aged 12-35 months who received the varicella vaccine. EXPOSURE: First-dose varicella vaccine. OUTCOMES AND MEASURES: All incident ICD-9-CM diagnoses (emergency or inpatient departments) occurring 1-56 days after the varicella vaccination were classified within a hierarchical system of diagnosis categories using Multi-Level Clinical Classifications Software. A self-controlled tree-temporal data mining tool was then used to explore the incidence of AE clustering with a variety of potential risk intervals. The comparison interval consisted of days in the 56-day follow-up period that fell outside the risk interval. RESULTS: Among 1,194,189 varicella vaccinees with no other same-day vaccinations, nine diagnoses with clustering features were categorized into four safety signals: fever on days 1-6 (attributable risk [AR] 38.5 per 100,000, p < 0.001), gastritis and duodenitis on days 1-2 (AR 5.9 per 100,000, p < 0.001), acute upper respiratory infection on days 1-5 (AR 11.0 per 100,000, p = 0.006), and varicella infection on days 1-9 (AR 2.7 per 100,000, p < 0.001). These safety profiles and their corresponding risk intervals have been identified in previous safety surveillance studies. CONCLUSIONS: Unexpected clusters of AEs were not detected after the mass administration of childhood varicella vaccines in Taiwan. The tree-temporal statistical method is a feasible approach to the safety surveillance of vaccines in populations of young children.
Subject(s)
Chickenpox Vaccine , Chickenpox , Chickenpox/epidemiology , Chickenpox/prevention & control , Chickenpox Vaccine/adverse effects , Child, Preschool , Humans , Immunization Programs , Infant , Vaccination/adverse effects , Vaccines, Attenuated/adverse effectsABSTRACT
The low vessel density and oxygen concentration in hypoxia are the main causes of reduced efficiency of anticancer therapeutics and can stimulate the tumor's relapse. Research showed that macrophages could cross the blood-vessel barriers and reach the hypoxic regions of tumors. Using macrophages in a drug delivery system has been a promising method for tumor targeting in recent years. In this work, we successfully modified monocyte chemoattractant protein-1 (MCP-1) and iron-based metal-organic framework (MIL-100(Fe)) on the photothermal agent, gold nanorods (GNRs) (i.e., MCP-1/GNR@MIL-100(Fe)), to increase cellular uptake and biocompatibility. The results of TEM, UV-vis, and FTIR all confirmed that we'd synthesized MCP-1/GNR@MIL-100(Fe) successfully, and the MCP-1/GNR@MIL-100(Fe) also showed good biocompatibility. A transwell migration assay illustrated that our material attracted macrophages, and the material uptake amount was increased by 1.5 times after MCP-1 functionalization. It also indicated that the macrophages have a tumor-targeting ability. In the in vivo experiment, we subcutaneously implanted U251 MG cells in nude mice as a xenograft model to demonstrate the photothermal activity of MCP-1/GNR@MIL-100(Fe). With successive NIR treatment, the tumor growth could be controlled, and the tumor volume still remained below 100 mm3 after laser treatment. MCP-1/GNR@MIL-100(Fe) combined with the laser treatment showed an excellent antitumor efficacy from the histology of tumor tissues, survival rates, and bioluminescence imaging.
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BACKGROUND: The relationship between apolipoprotein C3 (APOC3) gene polymorphisms and nonalcoholic fatty liver disease (NAFLD) risk has been investigated in many studies, with inconclusive findings. This meta-analysis evaluated the effect of APOC3 promoter region polymorphisms (-455T/C and -482C/T) on NAFLD susceptibility. METHODS: A comprehensive search of eligible studies up to October 2020 was performed on Medline, Embase, Web of Science, and Google Scholar databases. No restriction was imposed on language, publication date, or publication status. Odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated to assess the combined effect sizes. The levels of heterogeneity, sensitivity, subgroup, and publication bias were analyzed subsequently. RESULTS: This meta-analysis included eight studies, consisting of 1,511 patients with NAFLD and 1,900 controls fulfilling the inclusion criteria and exclusion criteria. The pooled analysis showed significant associations between APOC3 -455T/C polymorphism and NAFLD risk in allelic (OR = 1.33; 95% CI = 1.05-1.67), dominant (OR = 1.34; 95% CI = 1.04-1.72), and recessive (OR = 1.60; 95% CI = 1.06-2.40) models. Ethnicity-based stratification showed that -455T/C polymorphism was significantly associated with NAFLD risk in the non-Asian but not in the Asian population. No association was evident between -482C/T polymorphism and NAFLD risk. CONCLUSION: Our findings suggest that APOC3 promoter region polymorphism -455T/C may be associated with NAFLD risk in the non-Asian but not in the Asian population. Additional studies with other functional polymorphisms are needed to discover APOC3 gene effects on NAFLD.
Subject(s)
Apolipoprotein C-III/genetics , Genetic Predisposition to Disease , Non-alcoholic Fatty Liver Disease/genetics , Polymorphism, Single Nucleotide/genetics , HumansABSTRACT
BACKGROUND: The study was to compare the efficacy between IV peramivir and oral oseltamivir treatments in patients with influenza. METHODS: The PubMed, EMBASE, Scopus, ClinicalTrials.gov, and Cochrane Library databases were searched for studies published before January 2020. RESULTS: The meta-analysis was conducted to calculate the pooled effect size by using a random-effects model. Seven randomized controlled trials (RCTs) including 1,138 patients were reviewed. The incidence of total complications revealed no significant difference between 600 mg IV peramivir (P600) and 75 mg oral oseltamivir (O75) treatments (2.8% vs. 4.1%; risk ratio [RR] = 0.70; 95% confidence interval [CI]: 0.36-1.38). The incidence of pneumonia was not significantly different between the P600 and O75 treatment groups (2.2% vs. 2.7%; RR = 0.74; 95% CI: 0.37-1.51). Regarding the time to the alleviation of symptoms, no difference was found in P600 and O75 treatment (MD = -3.00; 95% CI: -11.07 to 5.06). The rate of fever clearance in 24 h and the time to fever resolution were not statistically different between the IV peramivir and oral oseltamivir treatments (at different dosages) groups. CONCLUSIONS: The treatment of influenza with IV peramivir or oral oseltamivir had similar clinical efficacy.
Subject(s)
Acids, Carbocyclic/administration & dosage , Guanidines/administration & dosage , Influenza, Human/drug therapy , Oseltamivir/administration & dosage , Administration, Intravenous , Administration, Oral , Antiviral Agents/administration & dosage , Humans , Influenza, Human/virology , Pneumonia/epidemiology , Pneumonia/virology , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Withaferin A is a functional ingredient of a traditional medicinal plant, Withania somnifera, which has been broadly used in India for protecting against chronic diseases. This bioactive steroidal lactone possesses multiple functions such as anti-oxidation, anti-inflammation, and immunomodulation. Chronic kidney disease (CKD) is one of the major health problems worldwide with the high complication, morbidity, and mortality rates. The detailed effects and underlying mechanisms of withaferin A on CKD progression still remain to be clarified. PURPOSE: We aimed to investigate whether withaferin A treatment ameliorates the development of renal fibrosis and its related mechanisms in a CKD mouse model. METHODS: A mouse model of unilateral ureteral obstruction (UUO) was used to mimic the progression of CKD. Male adult C57BL/6J mice were orally administered with 3 mg/kg/day withaferin A for 14 consecutive days after UUO surgery. Candesartan (5 mg/kg/day) was used as a positive control. RESULTS: Both Withaferin A and candesartan treatments significantly ameliorated the histopathological changes and collagen deposition in the UUO kidneys. Withaferin A could significantly reverse the increases in the protein levels of pro-fibrotic factors (fibronectin, transforming growth factor-ß, and α-smooth muscle actin), inflammatory signaling molecules (phosphorylated nuclear factor-κB-p65, interleukin-1ß, and cyclooxygenase-2), and cleaved caspase-3, apoptosis, and infiltration of neutrophils in the UUO kidneys. The protein levels of endoplasmic reticulum (ER) stress-associated molecules (GRP78, GRP94, ATF4, CHOP, phosphorylated eIF2α, and cleaved caspase 12) were increased in the kidneys of UUO mice, which could be significantly reversed by withaferin A treatment. CONCLUSION: Withaferin A protects against the CKD progression that is, at least in part, associated with the moderation of ER stress-related apoptosis, inflammation, and fibrosis in the kidneys of CKD. Withaferin A may serve as a potential therapeutic agent for the development of CKD.
Subject(s)
Apoptosis/drug effects , Endoplasmic Reticulum Stress/drug effects , Kidney/pathology , Nephritis/drug therapy , Withanolides/pharmacology , Animals , Benzimidazoles/pharmacology , Biphenyl Compounds , Disease Models, Animal , Endoplasmic Reticulum Chaperone BiP , Fibrosis , Kidney/drug effects , Kidney/metabolism , Male , Mice, Inbred C57BL , Nephritis/metabolism , Nephritis/pathology , Protective Agents/pharmacology , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/etiology , Signal Transduction/drug effects , Tetrazoles/pharmacology , Ureteral Obstruction/complications , Ureteral Obstruction/pathologyABSTRACT
BACKGROUND: Since 2006, two rotavirus vaccines have been licensed in Taiwan, either as a 2- (RV1) or 3-dose (RV5) schedule administered at ages 2, 4, and 6 months. This study assessed the risk of intussusception and Kawasaki disease (KD) associated with rotavirus vaccines among infants. METHODS: Cases of intussusception and KD in infants aged less than 365 days were identified from the National Health Insurance databases, from 1 January 2007 through 31 December 2014, using the first-ever ICD-9-CM diagnosis codes. Histories of rotavirus vaccination were obtained from the National Immunization Information System. The modified self-controlled case series design included vaccinated cases, and compared incidence rate ratios (IRRs) between the risk period (postvaccination days 1-21 [intussusception] or days 1-28 [KD]) and control period (ages 0-364 days outside the -14 to +21 [intussusception] or +28 [KD] days of vaccination) by each type and dose of vaccine. Conditional Poisson regression models were adjusted for age using age-in-week (7-day) categorization. RESULTS: Overall 2064 intussusception cases and 2079 KD cases were diagnosed in 567,726 recipients (5313 [0.9%] received both RV5 and RV1). An increase in intussusception risk was observed in the 1-7 days (IRR 12.59, 95% confidence interval [CI] 8.07-19.66) and 8-21 days (IRR 1.78, 95% CI 1.00-3.16) post dose 1 of RV1, but not RV5. Risk of KD was higher during the third week post dose 2 of RV5 (IRR 2.33, 95% CI 1.35-4.00), and fourth week post dose 1 of RV1 (IRR 1.98, 95% CI 1.16-3.40). CONCLUSION: Our finding of an increased risk of intussusception associated with RV1 in the first week after dose 1 is consistent with results of previous postlicensure studies. Further research should verify a potentially delayed risk of KD after rotavirus vaccination.