Role of low-density lipoprotein electronegativity and sexual dimorphism in contributing early ventricular tachyarrhythmias following ST-elevation myocardial infarction.

Background: Early ventricular tachycardia/fibrillation (VT/VF) in patients with ST-elevation myocardial infarction (STEMI) has higher morbidity and mortality. This study examines gender-differentiated risk factors and underlying mechanisms for early onset VT/VF in STEMI. Methods: We analyzed data from 2,964 consecutive STEMI patients between January 1, 2008 and December 31, 2021. Early VT/VF was defined as occurrence of spontaneous VT/VF of ≥30 s or requirement of immediate cardioversion/defibrillation within the first 48 h after symptoms. An ex vivo ischemic-reperfusion experiments were conducted in 8-week-old ApoE-/- mice fed a high-fat diet to explore the underlying mechanisms of early VT/VF. Results: In 255 of out 2,964 STEMI patients who experienced early VT/VF, the age was younger (58.6 ± 13.8 vs. 61.0 ± 13.0 years old, P = 0.008) with a male predominance. The plasma levels of L5, the most electronegative subclass of low-density lipoprotein, was higher in early VT/VF patients compared to those without early VT/VF (n = 21, L5: 14.1 ± 22.6% vs. n = 46, L5: 4.3 ± 9.9%, P = 0.016). In the experimental setup, all male mice (n = 4) developed VT/VF post sham operation, whereas no such incidence was observed in the female mice (n = 3). Significantly, male mice exhibited considerably slower cardiac conduction velocity as compared to their female counterparts in whole heart preparations (25.01 ± 0.93 cm/s vs.42.32 ± 5.70 cm/s, P < 0.001), despite analogous action potential durations. Furthermore, isolated ventricular myocytes from male mice showed a distinctly lower sodium current density (-29.20 ± 3.04 pA/pF, n = 6) in comparison to female mice (-114.05 ± 6.41 pA/pF, n = 6, P < 0.001). This decreased sodium current density was paralleled by a reduced membrane expression of Nav1.5 protein (0.38 ± 0.06 vs. 0.89 ± 0.09 A.U., P < 0.001) and increased cytosolic Nav1.5 levels (0.59 ± 0.06 vs. 0.29 ± 0.04 A.U., P = 0.001) in male mice. Furthermore, it was observed that the overall expressions of sorting nexin 27 (SNX27) and vacuolar protein sorting 26 (VPS26) were significantly diminished in male mice as compared to female littermates (0.91 ± 0.15 vs. 1.70 ± 0.28, P = 0.02 and 0.74 ± 0.09 vs. 1.57 ± 0.13, P < 0.01, respectively). Conclusions: Our findings reveal that male STEMI patients with early VT/VF are associated with elevated L5 levels. The gender-based discrepancy in early VT/VF predisposition might be due to compromised sodium channel trafficking, possibly linked with increased LDL electronegativity.

Three-dimensional evaluation of skeletal stability after surgery-first bimaxillary surgery for class III asymmetry in 70 consecutive patients.

Background/purpose: Skeletal stability after orthognathic surgery is essential for positive treatment outcome. This study evaluated the stability of osteotomy segments after surgery-first bimaxillary surgery for class III asymmetry. Materials and methods: Seventy adults with class III asymmetry consecutively corrected through surgery-first Le Fort I and bilateral sagittal split osteotomies were investigated. Cone-beam computed tomography before treatment (T0), 1-week after surgery (T1), and after all treatment (T2, ≥1-year after surgery) was used to assess surgical movement (T0 to T1) and skeletal stability (T1 to T2) regarding the translation and rotation of the maxillary, mandibular distal, and proximal segments. Results: At T1, the maxillary segment had moved forward and upward, turned to the deviated side, and rotated downward (all P < 0.01). The distal segment of mandible had moved forward and upward and rotated upward (all P < 0.001). The deviated proximal segment had moved upward, tilted to the opposite side, and rotated upward (all P < 0.001). The opposite proximal segment had moved upward and tilted to the deviated side (both P < 0.01). At T2, significant relapse occurred in the mandible. The distal segment moved forward and upward and rotated upward (all P < 0.001). The deviated proximal segment moved upward, tilted to the opposite side, and rotated upward (all P < 0.001). The opposite proximal segment moved upward and tilted to the deviated side (both P < 0.01). Conclusion: Clinically significant relapse of class III asymmetry was discovered on the mandibular distal and opposite proximal segments.

Surgery-First Orthognathic Approach for Correction of Dentofacial Deformity in Unilateral Cleft Lip and Palate.

BACKGROUND: Although several studies have reported the advantages of the surgery-first approach for orthognathic correction of class III deformity, there is no report of the success of this approach for patients with cleft lip and palate. Therefore, the purpose of this study was to evaluate the stability and outcome of bimaxillary surgery for cleft-related dentofacial deformity using a surgery-first approach. METHODS: Forty-one patients with unilateral cleft lip and palate who consecutively underwent Le Fort I and bilateral sagittal split osteotomies for skeletal class III deformity were included. Cone-beam computed tomographic scans before surgery, 1 week after surgery, and after orthodontic treatment were used to measure the surgical and postsurgical changes in jaw position by landmarks, and outcomes of jaw protrusion and relation, incisor angle and occlusion, and menton deviation after treatment. Self-report questionnaires regarding satisfaction with overall appearance of the face and seven facial regions were administered after treatment. RESULTS: A clinically insignificant relapse was found in the maxilla (<1 mm) and mandible (<2 mm). There was a significant improvement in the jaw protrusion and relation, incisor angle and occlusion, and menton deviation. Responses from the self-report questionnaires completed after treatment indicated that patient satisfaction was high. CONCLUSION: These findings demonstrate surgical-orthodontic treatment with a surgery-first approach can successfully improve cleft-related dentofacial deformity in patients with unilateral cleft lip and palate. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Surgical occlusion setup and skeletal stability of correcting cleft-associated class III deformity using surgery-first bimaxillary surgery.

BACKGROUND: This study aimed to assess the three-dimensional (3D) quantitative characteristics of the surgical occlusion setup in surgery-first cleft orthognathic surgery, and to evaluate its influence on post-surgical skeletal stability. METHODS: This prospective study was comprised of 35 patients with unilateral cleft lip and palate and class III deformity who consecutively underwent two-jaw surgery with surgery-first approach. Digitized dental models were analyzed to quantify the 3D characteristics of the final surgical occlusion setup. Cone-beam computed tomography was used to measure the 3D surgical skeletal movement and post-surgical skeletal stability. The correlation between skeletal stability and surgical occlusal contact or surgical skeletal movement was also evaluated. RESULTS: The surgical occlusion setup had a large incisor overjet and positive overbite, and buccal cross bite and open bite on second molars. Occlusal contact on three segments was present in 51.4% of the patients, and the average number for tooth contact was 4.3 teeth. No correlation was found between maxillary or mandibular stability and surgical occlusal contact. However, a significant correlation was found between maxillary and mandibular stability and the surgical skeletal movement. CONCLUSIONS: The surgical occlusion for correction of cleft-associated class III deformity using the surgery-first approach was characterized with large overjet and positive overbite, and posterior cross bite and open bite. On average, there was occlusal contact on four to five teeth; half of surgical occlusion setups had contact on three segments. The post-surgical skeletal stability was not related to the surgical occlusal contact but to the surgical skeletal movement.

A Common East Asian aldehyde dehydrogenase 2*2 variant promotes ventricular arrhythmia with chronic light-to-moderate alcohol use in mice.

Chronic heavy alcohol use is associated with lethal arrhythmias. Whether common East Asian-specific aldehyde dehydrogenase deficiency (ALDH2*2) contributes to arrhythmogenesis caused by low level alcohol use remains unclear. Here we show 59 habitual alcohol users carrying ALDH2 rs671 have longer QT interval (corrected) and higher ventricular tachyarrhythmia events compared with 137 ALDH2 wild-type (Wt) habitual alcohol users and 57 alcohol non-users. Notably, we observe QT prolongation and a higher risk of premature ventricular contractions among human ALDH2 variants showing habitual light-to-moderate alcohol consumption. We recapitulate a human electrophysiological QT prolongation phenotype using a mouse ALDH2*2 knock-in (KI) model treated with 4% ethanol, which shows markedly reduced total amount of connexin43 albeit increased lateralization accompanied by markedly downregulated sarcolemmal Nav1.5, Kv1.4 and Kv4.2 expressions compared to EtOH-treated Wt mice. Whole-cell patch-clamps reveal a more pronounced action potential prolongation in EtOH-treated ALDH2*2 KI mice. By programmed electrical stimulation, rotors are only provokable in EtOH-treated ALDH2*2 KI mice along with higher number and duration of ventricular arrhythmia episodes. The present research helps formulate safe alcohol drinking guideline for ALDH2 deficient population and develop novel protective agents for these subjects.

Comparison of regional soft tissue changes after bimaxillary rotational surgery between class III deformity with overbite and open bite: A 3D imaging analysis.

BACKGROUND: This prospective study aimed to compare regional soft tissue changes between patients with class III overbite and open bite deformities treated with bimaxillary surgery involving clockwise and counter-clockwise mandibular setback, respectively. MATERIAL AND METHODS: Class III deformity adults receiving Le Fort I and bilateral sagittal split osteotomies were grouped according to the incisal occlusion: overbite (n = 30) and open bite (n = 30). Combined cone-beam CT scans and 3D facial photographs preoperative and at least 1-year postoperative were taken to assess the soft tissue changes. RESULTS: Postoperative changes for the overbite and open bite groups included anterior repositioning of nose (-0.8 ± 1.2 mm and -1.1 ± 1.1 mm, respectively) and cheek (-1.9 ± 1.3 mm and -1.7 ± 2.6 mm, respectively), posterior repositioning of chin (5.2 ± 4.0 mm and 4.9 ± 3.2 mm, respectively), and medial (-1.7 ± 2.0 mm and -1.9 ± 2.1 mm, respectively) and posterior (2.7 ± 1.4 mm and 2.8 ± 2.3 mm, respectively) repositioning of bilateral angles. Posterior (1.2 ± 2.0 mm and 5.1 ± 3.3 mm) and inferior (-1.4 ± 2.2 mm and -2.4 ± 2.7 mm) repositioning of upper lip and lower lip occurred in overbite group. Inferior (-2.3 ± 2.4 mm) and superior (3.7 ± 3.4 mm) repositioning of chin occurred in the overbite and open bite groups, respectively. CONCLUSIONS: Treatment of class III overbite and open bite deformities with bimaxillary rotational surgery resulted in comparable regional soft tissue changes, except for upper lip, lower lip and chin.

PD-L1 and AKT Overexpressing Adipose-Derived Mesenchymal Stem Cells Enhance Myocardial Protection by Upregulating CD25+ T Cells in Acute Myocardial Infarction Rat Model.

This study explores the synergistic impact of Programmed Death Ligand 1 (PD-L1) and Protein Kinase B (Akt) overexpression in adipose-derived mesenchymal stem cells (AdMSCs) for ameliorating cardiac dysfunction after myocardial infarction (MI). Post-MI adult Wistar rats were allocated into four groups: sham, MI, ADMSC treatment, and ADMSCs overexpressed with PD-L1 and Akt (AdMSC-PDL1-Akt) treatment. MI was induced via left anterior descending coronary artery ligation, followed by intramyocardial AdMSC injections. Over four weeks, cardiac functionality and structural integrity were assessed using pressure-volume analysis, infarct size measurement, and immunohistochemistry. AdMSC-PDL1-Akt exhibited enhanced resistance to reactive oxygen species (ROS) in vitro and ameliorated MI-induced contractile dysfunction in vivo by improving the end-systolic pressure-volume relationship and preload-recruitable stroke work, together with attenuating infarct size. Molecular analyses revealed substantial mitigation in caspase3 and nuclear factor-κB upregulation in MI hearts within the AdMSC-PDL1-Akt group. Mechanistically, AdMSC-PDL1-Akt fostered the differentiation of normal T cells into CD25+ regulatory T cells in vitro, aligning with in vivo upregulation of CD25 in AdMSC-PDL1-Akt-treated rats. Collectively, PD-L1 and Akt overexpression in AdMSCs bolsters resistance to ROS-mediated apoptosis in vitro and enhances myocardial protective efficacy against MI-induced dysfunction, potentially via T-cell modulation, underscoring a promising therapeutic strategy for myocardial ischemic injuries.

Shegan Mahuang Decoction May Reduce Airway Inflammation in Neutrophilic Asthmatic Mice by Improving the Mitochondrial Function of Bronchoalveolar Lavage Fluid Exosomes.

Asthma is a common pulmonary disease mainly caused by the infiltration of neutrophils. There is a limit to the therapeutic effects of the available asthma drugs on neutrophilic asthma. Shegan Mahuang Decoction (SMD) is one of the representative traditional Chinese medicine (TCM) prescriptions for asthma, and it can effectively relieve the clinical symptoms of patients. However, the effect of SMD on the treatment of neutrophilic asthma remains unknown. In this study, a mouse model of neutrophilic asthma induced by lipopolysaccharide (LPS)/ovalbumin (OVA) was established, and the effect of a modified SMD prescription on the model was evaluated. After treatment, SMD was demonstrated to be therapeutically effective on asthmatic mice via airway resistance detection and lung pathology and was able to affect cytokine levels in vivo. Further experiments verified that SMD regulated the expression of mitochondrial function proteins in bronchoalveolar lavage fluid (BALF) exosomes. The results demonstrate that SMD confers a therapeutic effect on a neutrophilic asthma mouse model, and it may reduce neutrophil airway inflammation by regulating myeloid-derived regulatory cell (MDRC) function and airway exosome mitochondrial function.

Acute and Subacute Toxicity of Fluorescent Gold Nanoclusters Conjugated with α-Lipoic Acid.

Fluorescent gold nanoclusters conjugated with α-lipoic acid (FANC) is a promising biocompatible fluorescent nanomaterial with a high potential for drug development. However, there is still no FANC-related research on toxicology, which is very important for future research and the development of healthy food supplements or drugs. This study uses oral administration of FANC to determine the most appropriate dose range in ICR mice for further evaluation. The in vivo acute and subacute toxicity study was conducted by oral administration of FANC to male and female ICR mice. Animal survival, body weight, daily food consumption, hematological profile, organ coefficient, serum biochemistry profile, and histopathological changes were analyzed. FANC did not show any form of morbidity or mortality at acute and subacute toxicity in both male and female ICR mice. Animal behavior, daily food consumption, hematological profile, organ coefficient, and histopathology showed no treatment-related malignant changes at single and repeated doses. Furthermore, serum glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), and creatinine (CRE) levels showed no significant malignant changes, which indicated that FANC does not cause liver and renal damage. The only change observed in this study was the change in body weight. The body weight of the FANC-treated group was slightly decreased in female mice but increased in male mice; however, the body weight decreases were below the threshold of concern, and there was no dose-response effect. In conclusion, no observed adverse effect level (NOAEL) in repeated doses was considered in 20 µM/100 µL/25 g male and female ICR mice.

Effect of the prosthetic index on stress distribution in Morse taper connection implant system and peri-implant bone: a 3D finite element analysis.

BACKGROUND: The combination of a prosthetic index with Morse taper connection was developed, with the purpose of making prosthetic procedures more precise. However, the presence of the index may compromise the mechanical performance of the abutment. The aim of this study is to evaluate the effect of prosthetic index on stress distribution in implant-abutment-screw system and peri-implant bone by using the 3D finite element methodology. METHODS: Two commercial dental implant systems with different implant-abutment connections were used: the Morse taper connection with platform switching (MT-PS) implant system and the internal hex connection with platform matching (IH-PM) implant system. Meanwhile, there are two different designs of Morse taper connection abutment, namely, abutments with or without index. Consequently, three different models were developed and evaluated: (1) MT-PS indexed, (2) MT-PS non-indexed, and (3) IH-PM. These models were inserted into a bone block. Vertical and oblique forces of 100 N were applied to each abutment to simulate occlusal loadings. RESULTS: For the MT-PS implant system, the maximum stress was always concentrated in the abutment neck under both vertical and oblique loading. Moreover, the maximum von Mises stress in the neck of the MT-PS abutment with index even exceed the yield strength of titanium alloy under the oblique loading. For the IH-PM implant system, however, the maximum stress was always located at the implant. Additionally, the MT-PS implant system has a significantly higher stress level in the abutment neck and a lower stress level around the peri-implant bone compared to the IH-PM implant system. The combined average maximum stress from vertical and oblique loads is 2.04 times higher in the MT-PS indexed model, and 1.82 times for the MT-PS non-indexed model than that of the IH-PM model. CONCLUSIONS: MT-PS with index will cause higher stress concentration on the abutment neck than that of without index, which is more prone to mechanical complications. Nevertheless, MT-PS decreases stress within cancellous bone and may contribute to limiting crestal bone resorption.

Impact of Pain, Agitation, and Delirium Bundle on Delirium and Cognitive Function.

BACKGROUND: Differences in short-term cognitive function between mechanically ventilated patients treated with multicomponent interventions and those receiving routine nursing care have not been established because of the lack of follow-up in previous studies. PURPOSE: This study was designed to evaluate the effects of the pain, agitation, and delirium (PAD) care bundle on delirium occurrence and clinical outcomes, specifically in terms of short-term cognitive function, in mechanically ventilated patients. METHODS: Data on 243 patients with mechanical ventilation were analyzed from January 2017 to February 2019. The eligible patients were divided randomly into two groups. The control group ( n = 120) received usual care, whereas the intervention group ( n = 123) received the PAD bundle, including pain monitoring and management, light sedation and daily awakening, early mobility, sleep promotion, and delirium monitoring. The incidence and duration of delirium, ventilator time, and intensive care unit (ICU) length of stay were compared between the two groups. Upon discharge from the ICU and at 3 and 6 months after discharge, cognitive function was assessed using the Montreal Cognitive Assessment scale and compared between the two groups. RESULTS: The incidence of delirium was reduced significantly in the intervention group, and significant decreases in the duration of delirium, ventilator time, and ICU length of stay were found. Cognitive impairment in the intervention group was significantly lower at the 3-month follow-up assessment. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The PAD bundle was shown to be associated with a lower incidence of delirium and improved clinical outcomes. Short-term cognitive impairment occurred in fewer patients who were managed with the PAD bundle after ICU discharge. Our findings indicate that the PAD bundle has the potential to improve clinical outcomes. The administrative staff of ICUs should use strategies, such as interdisciplinary teamwork, to facilitate the buy-in and implementation of interventions.

Is the pattern of mandibular asymmetry in mild craniofacial microsomia comparable to non-syndromic class II asymmetry?

OBJECTIVES: To compare the characteristics of mandibular asymmetry in patients with unilateral craniofacial microsomia (CFM) and class II asymmetry. MATERIALS AND METHODS: Pretreatment cone-beam computed tomography of consecutive adults with Pruzansky-Kaban type I and IIA CFM (CFM group) was analyzed by 3D cephalometry. Fourteen mandibular landmarks and two dental landmarks were identified. The mandibular size and positional asymmetry were calculated by using landmark-based linear and volumetric measurements, in terms of asymmetry ratios (affected/non-affected side) and absolute differences (affected - non-affected side). Results were compared with non-syndromic class II with matched severity of chin deviation (Class II group). Statistical analyses included independent t test, paired t test, chi-square test, and ANOVA. RESULTS: CFM group (n, 21; mean age, 20.4 ± 2.5 years) showed significantly larger size asymmetry in regions of mandibular body, ramus, and condyle compared to Class II group (n, 21; mean age, 27.8 ± 5.9 years) (p < 0.05). The curvature of mandibular body was asymmetric in CFM. Regarding the positional asymmetry of mandibular body, while a comparable transverse shift and a negligible yaw rotation were found among the two groups, the roll rotation in CFM was significantly greater as well as the occlusal (6.06° vs. 4.17°) and mandibular (7.84° vs. 2.80°) plane cants (p < 0.05). CONCLUSIONS: Mild CFM showed significantly more severe size asymmetry and roll rotation in mandible than non-CFM class II asymmetry. CLINICAL RELEVANCE: To improve the mandibular size and positional asymmetry in CFM, adjunct hard tissue augmentation or reduction in addition to OGS orthodontics with a meticulous roll and yaw planning is compulsory, which is expected to be distinct from treating non-CFM class II asymmetry.

Three-Dimensional Analysis of the Condylar Hypoplasia and Facial Asymmetry in Craniofacial Microsomia Using Cone-Beam Computed Tomography.

PURPOSE: To assess the condylar hypoplasia and its correlation with craniofacial deformities in adults with unilateral craniofacial microsomia (CFM). METHODS: Pretreatment cone-beam computed tomography scans of consecutive adults (mean age: 20.4 ± 3.0 years; range: 17.3 to 31.4 years) with Pruzansky-Kaban type I and IIA CFM were reconstructed in 3D. Both condyles were segmented. Asymmetry ratios (affected side/contralateral side) of condylar volume were calculated to indicate the extent of condylar hypoplasia. 3D cephalometry was performed to quantify the maxillomandibular morphology and facial asymmetry. The correlations in between were assessed by using Pearson's or Spearman's correlation coefficients. RESULTS: Thirty-six subjects were enrolled, consisting of 22 subjects with Pruzansky-Kaban type I and 14 subjects with type IIA. The condyles in type IIA group were significantly more hypoplastic in height (asymmetry ratio: 40.69 vs 59.95%, P = .006) and volume (18.16 vs 47.84%, P < .001) compared to type I group. Type IIA group had a significantly smaller SNB value than type I group (72.94° vs 77.41°, P = .012), and a significantly greater facial asymmetry (P < .05). The hypoplastic extent of condylar volume and Pruzansky-Kaban types were significantly correlated with SNB (r = 0.457 and ρ = -0.411, respectively), upper incisor deviation (r = -0.446 and ρ = 0.362), chin deviation (r = -0.477 and ρ = 0.527), upper occlusal plane cant (r = -0.672 and ρ = 0.631), and mandibular plane cant (r = -0.557 and ρ = 0.357, P < .05). CONCLUSION: For unilateral CFM adults, greater condylar hypoplasia in volume along with more severe mandibular retrusion and facial asymmetry objectively indicated a higher scale of Pruzansky-Kaban classification (type IIA). These quantitative distinctions are expected to enhance the diagnostic reliability of CFM.

Inhibition of chondrocyte apoptosis in a rat model of osteoarthritis by exosomes derived from miR­140­5p­overexpressing human dental pulp stem cells.

Osteoarthritis (OA) is a common joint disorder, and the restoration of the impaired cartilage remains a main concern for researchers and clinicians. MicroRNAs (miRNAs or miRs) play crucial roles in the pathogenesis of OA. The present study examined the therapeutic efficacy of exosomal­miR­140­5p for the treatment of OA using dental pulp stem cells (DPSCs). The findings indicated that the exosomal burden of miR­140­5p was substantially increased following the transfection of DPSCs with miR­140­5p mimic. The administration of DPSC­derived exosomes promoted chondrocyte­related mRNA expression, including aggrecan, Col2α1 and Sox9, in interleukin (IL)­1ß­treated human chondrocytes. This effect was substantially enhanced by miR­140­5p­enriched exosomes. The results further revealed that miR­140­5p­enriched exosomes induced a more significant reduction in IL­1ß­induced chondrocyte apoptosis than the DPSC­derived exosomes. Mechanistically, it was found that miR­140­enriched DPSC­derived exosomes exerted anti­apoptotic effects, probably by regulating the expression levels of apoptosis­related proteins. Furthermore, multiple administrations of miR­140­5p­enriched exosomes substantially improved knee joint conditions in a rat model of OA. Collectively, the data of the present study suggest that exosomes derived from genetically modified DPSCs may prove to be a potential strategy for the treatment of OA.

Nanomedicine and Early Cancer Diagnosis: Molecular Imaging using Fluorescence Nanoparticles.

Incorporating nanotechnology into fluorescent imaging and magnetic resonance imaging (MRI) has shown promising potential for accurate diagnosis of cancer at an earlier stage than the conventional imaging modalities. Molecular imaging (MI) aims to quantitatively characterize, visualize, and measure the biological processes or living cells at molecular and genetic levels. MI modalities have been exploited in different applications including noninvasive determination and visualization of diseased tissues, cell trafficking visualization, early detection, treatment response monitoring, and in vivo visualization of living cells. High-affinity molecular probe and imaging modality to detect the probe are the two main requirements of MI. Recent advances in nanotechnology and allied modalities have facilitated the use of nanoparticles (NPs) as MI probes. Within the extensive group of NPs, fluorescent NPs play a prominent role in optical molecular imaging. The fluorescent NPs used in molecular and cellular imaging can be categorized into three main groups including quantum dots (QDs), upconversion, and dyedoped NPs. Fluorescent NPs have great potential in targeted theranostics including cancer imaging, immunoassay- based cells, proteins and bacteria detections, imaging-guided surgery, and therapy. Fluorescent NPs have shown promising potentials for drug and gene delivery, detection of the chromosomal abnormalities, labeling of DNA, and visualizing DNA replication dynamics. Multifunctional NPs have been successfully used in a single theranostic modality integrating diagnosis and therapy. The unique characteristics of multifunctional NPs make them potential theranostic agents that can be utilized concurrently for diagnosis and therapy. This review provides the state of the art of the applications of nanotechnologies in early cancer diagnosis focusing on fluorescent NPs, their synthesis methods, and perspectives in clinical theranostics.

Partitioned Extracts of Bauhinia championii Induce G0/G1 Phase Arrest and Apoptosis in Human Colon Cancer Cells.

Bauhinia championii (Benth.) is one of the commonly used herbs in Taiwan. The stem of this plant has been used to treat epigastria pain and rheumatoid arthritis. However, the antitumor activities of this herb have never been reported. This study aims to investigate the mechanism of anticancer activity of the extracts from B. championii (BC). BC was fractionated with a series of organic solvents, including n-hexane (H), ethyl acetate (EA), 1-butanol (B), and water (W). We first investigated the effects of BC-H, BC-EA, BC-B and BC-W partitioned fraction on cell viability. In HCT 116 colon cancer cell lines, BC-EA showed the highest inhibition of cell viability and changed the morphology of cells. With dose- and time-dependent manners, BC-EA inhibited the proliferation of HCT 116 cells by inducing apoptosis and G0/G1 phase arrest of cell cycle. To determine the underlying mechanisms, down-regulated CDK2, Cyclin D, and Cyclin E and up-regulated p16, p21, and p53 may account for the cell cycle arrest, while the apoptotic effect of BC-EA may attribute to increased intracellular Ca2+, loss of mitochondria membrane potential (ΔΨm), increase of Bax, Bak, puma, and AIF, and decrease of Bcl-2. Furthermore, the inactivation of Ras signaling pathway by BC-EA also contributed to its apoptotic effect on HCT 116. Our study demonstrates that BC-EA not only inhibits cell growth but also induces apoptosis through inhibiting Ras signal pathway and increasing p53 expression levels. We suggest that BC-EA may be a new dietary supplement and a useful tool to search for therapeutic candidates against colon cancer.

Three-dimensional characterization of mandibular asymmetry in craniofacial microsomia.

OBJECTIVES: This study aimed to investigate the three-dimensional (3D) mandibular asymmetry in craniofacial microsomia (CFM) and its association with the Pruzansky-Kaban classification system. MATERIALS AND METHODS: Cone-beam computed tomography images of 48 adult CFM cases were collected. The asymmetry of the mandibular body and ramus was analyzed with 3D landmarks. The mirrored mandibular model was registered on the original model, yielding a color-coded distance map and an average distance (i.e., asymmetry score) to quantify the overall mandibular asymmetry. RESULTS: The lengths of the mandibular body and ramus were significantly shorter on the affected than the contralateral side (p < 0.001). The ANB (p = 0.009), body and ramal lengths (both p < 0.001), and body and ramal length asymmetry (both p < 0.05) were significantly different between mild (types I/IIA) and severe (types IIB/III) cases. The mandibular asymmetry score correlated with mandibular body length asymmetry (r = 0.296, p = 0.046). CFM mandibles showed high variability in shape asymmetry. CONCLUSIONS: CFM patients showed distinct body and ramal length asymmetries. In severe cases, mandibles were smaller, more retruded, and more asymmetric in length. The mandibular shape asymmetry was highly variable regardless of the Pruzansky-Kaban types, being a determinant in the extent of overall mandibular asymmetry. CLINICAL RELEVANCE: The 3D morphologic analysis provides better insights into real mandibular asymmetry. Although the Pruzansky-Kaban classification was applied, high individual variability of the mandibular morphology still existed within the types. Therefore, individualized analyses and treatment plans for CFM patients are highly recommended.

Role of apolipoprotein E in electronegative low-density lipoprotein-induced mitochondrial dysfunction in cardiomyocytes.

OBJECTIVE: L5, a highly electronegative subtype of low-density lipoprotein (LDL), is likely associated with the development of atherosclerosis and cardiovascular diseases. Normal LDL is composed mainly of apolipoprotein (Apo) B, but L5 has additional proteins such as ApoE. We previously demonstrated that L5 induces endothelial cell senescence by increasing mitochondrial reactive oxygen species. In the present study, we examined the effect of L5 on mitochondrial function in cardiomyocytes. METHODS: We used the Seahorse XF24 extracellular flux analyzer to examine the effect of L5 and its components on mitochondrial energy production. The effects of L5 on mitochondrial morphology were examined by immunofluorescence using MitoTracker Green FM and the corresponding probes in H9c2 cardiomyoblasts. Mitochondrial permeability was assessed by using a calcium-induced swelling assay with a voltage-dependent anion-selective channel (VDAC) inhibitor to determine VDAC-dependence both in vitro and in vivo. L5 without ApoE, referred to as △L5, was used to clarify the role of ApoE in L5-induced mitochondrial dysfunction. RESULTS: L5 not only significantly decreased basal (P < 0.05) and maximal respiration (P < 0.01) but also reduced spare respiratory capacity (P < 0.01) in H9c2 cells. Additionally, L5 caused phosphorylation of Drp1 and mitochondrial fission. Recombinant ApoE mimicked the mitochondrial effects of L5, but △L5 did not cause similar effects. After entering cells, ApoE on L5 colocalized with mitochondrial VDAC and caused mitochondria swelling both in vitro and in vivo. This effect was also seen with recombinant ApoE but not △L5. CONCLUSIONS: ApoE may play an important role in electronegative LDL-induced mitochondrial dysfunction through the opening of the mitochondrial permeability transition pore via the interaction of ApoE and VDAC.

Cardiac protection of Bauhinia championii against reperfusion injury.

This study aims to investigate the protective effects of the Bauhinia championii (BC) against ischemia/reperfusion (I/R)-induced injury in an isolated heart model. Langendorff-perfused C57BL/6JNarl mice hearts were performed with 30 minutes ischemia and 60 minutes reperfusion by left anterior descending artery ligation. Before reperfusion, boiling water extracts of BC (10 mg/L) was pretreated for 15 minutes. During reperfusion, BC significantly decreased the occurrence of ventricular arrhythmias by lead II electrocardiogram (ECG). Electrophysiological effect of BC was further determined in isolated ventricular myocytes by whole-cell patch clamp technique. The underlying mechanism may result from its Na+ channel blocking activity characterized with reduced rise slope of action potential and Na+ current density. Moreover, BC dramatically reduced I/R-caused infarct size, which was accessed by 2,3,5-triphenyltetrazolium chloride (TTC) assay. Since BC decreased I/R-induced myoglobin release and oxidation of Ca2+ -calmodulin-dependent protein kinase, inhibition of myocardial necroptosis may account for the protective effects of BC on myocytes lose. This study indicated that BC may prevent I/R induced ventricular arrhythmias and myocyte death by blocking Na+ channels and decreasing necroptosis, respectively. Since most of the available antiarrhythmic remedies have unwanted adverse actions, BC could be a novel candidate for the treatment of myocardial infarction and ventricular arrhythmia.

Recent advances in the use of microcarriers for cell cultures and their ex vivo and in vivo applications.

Microcarriers are 100- to 300-micron support matrices that permit the growth of adherent cells in bioreactor systems. They have a larger surface area to volume ratio in comparison to single cell monolayers, enabling cost-effective cell production and expansion. Microcarriers are composed of a solid matrix that must be separated from expanded cells during downstream processing stages. The detachment method is chosen on the basis of several factors like cell type, microcarrier surface chemistry, cell confluency and degree of aggregation. The development of microcarriers with a range of physiochemical properties permit controlled cell and protein associations that hold utility for novel therapeutics. In this review, we provide an overview of the recent advances in microcarrier cell culture technology. We also discuss its significance as an ex vivo research tool and the therapeutic potential of newly designed microcarrier systems in vivo.