Structural and functional reorganization of inhibitory synapses by activity-dependent cleavage of neuroligin-2.

Recent evidence has demonstrated that the transsynaptic nanoscale organization of synaptic proteins plays a crucial role in regulating synaptic strength in excitatory synapses. However, the molecular mechanism underlying this transsynaptic nanostructure in inhibitory synapses still remains unclear and its impact on synapse function in physiological or pathological contexts has not been demonstrated. In this study, we utilized an engineered proteolysis technique to investigate the effects of acute cleavage of neuroligin-2 (NL2) on synaptic transmission. Our results show that the rapid cleavage of NL2 led to impaired synaptic transmission by reducing both neurotransmitter release probability and quantum size. These changes were attributed to the dispersion of RIM1/2 and GABAA receptors and a weakened spatial alignment between them at the subsynaptic scale, as observed through superresolution imaging and model simulations. Importantly, we found that endogenous NL2 undergoes rapid MMP9-dependent cleavage during epileptic activities, which further exacerbates the decrease in inhibitory transmission. Overall, our study demonstrates the significant impact of nanoscale structural reorganization on inhibitory transmission and unveils ongoing modulation of mature GABAergic synapses through active cleavage of NL2 in response to hyperactivity.

Activation of the PERK-CHOP signaling pathway during endoplasmic reticulum stress contributes to olanzapine-induced dyslipidemia.

Olanzapine (OLZ) is a widely prescribed antipsychotic drug with a relatively ideal effect in the treatment of schizophrenia (SCZ). However, its severe metabolic side effects often deteriorate clinical therapeutic compliance and mental rehabilitation. The peripheral mechanism of OLZ-induced metabolic disorders remains abstruse for its muti-target activities. Endoplasmic reticulum (ER) stress is implicated in cellular energy metabolism and the progression of psychiatric disorders. In this study, we investigated the role of ER stress in the development of OLZ-induced dyslipidemia. A cohort of 146 SCZ patients receiving OLZ monotherapy was recruited, and blood samples and clinical data were collected at baseline, and in the 4th week, 12th week, and 24th week of the treatment. This case-control study revealed that OLZ treatment significantly elevated serum levels of endoplasmic reticulum (ER) stress markers GRP78, ATF4, and CHOP in SCZ patients with dyslipidemia. In HepG2 cells, treatment with OLZ (25, 50 µM) dose-dependently enhanced hepatic de novo lipogenesis accompanied by SREBPs activation, and simultaneously triggered ER stress. Inhibition of ER stress by tauroursodeoxycholate (TUDCA) and 4-phenyl butyric acid (4-PBA) attenuated OLZ-induced lipid dysregulation in vitro and in vivo. Moreover, we demonstrated that activation of PERK-CHOP signaling during ER stress was a major contributor to OLZ-triggered abnormal lipid metabolism in the liver, suggesting that PERK could be a potential target for ameliorating the development of OLZ-mediated lipid dysfunction. Taken together, ER stress inhibitors could be a potentially effective intervention against OLZ-induced dyslipidemia in SCZ.

Assessment of the Clinical Utility of the FilmArrayTM Gastrointestinal Panel for Detecting Gastrointestinal Pathogens.

BACKGROUND: Gastrointestinal infections present a significant public health concern as they lead to diverse clinical presentations and healthcare challenges. The rapid and accurate identification of causative pathogens is imperative for effective patient management. This study aimed to assess the clinical utility of the FilmArrayTM Gastrointestinal (GI) Panel for detecting gastrointestinal pathogens. METHODS: Between November 1, 2022, and December 31, 2023, we analysed gastrointestinal specimens collected from a cohort of patients aged 21 to 91 at Asia University Hospital. These specimens were analyzed using the FilmArrayTM GI Panel. RESULTS: The study included 76 patients for whom the FilmArrayTM GI assay was conducted, with 40 (52.6%) showing positive results. Among the positive specimens, 23 (57.5%) had a single pathogen, while the remaining 17 (42.5%) had multiple pathogens. The remaining 36 (47.4%) specimens showed no pathogens. The overall positivity rate of the specimens was 52.6%. The most frequently detected pathogens included Salmonella, Clostridium difficile (toxin A/B), and Enteropathogenic Escherichia coli (EPEC). CONCLUSIONS: This study underscores the clinical value of the FilmArrayTM GI assay as a rapid and reliable tool for diagnosing gastrointestinal infections. Its capacity to detect multiple pathogens simultaneously enhances diagnostic accuracy and gives information to use in clinical decision-making. We strongly recommend its integration into clinical practice to expedite the diagnosis and management of gastrointestinal infections, ultimately leading to improved patient care and healthcare efficiency.

Free Water MR Imaging of White Matter Microstructural Changes is a Sensitive Marker of Amyloid Positivity in Alzheimer's Disease.

BACKGROUND: Extracellular free water (FW) resulting from white matter degeneration limits the sensitivity of diffusion tensor imaging (DTI) in predicting Alzheimer's disease (AD). PURPOSE: To evaluate the sensitivity of FW-DTI in detecting white matter microstructural changes in AD. To validate the effectiveness of FW-DTI indices to predict amyloid-beta (Aß) positivity in mild cognitive impairment (MCI) subtypes. STUDY TYPE: Retrospective. POPULATION: Thirty-eight Aß-negative cognitively healthy (CH) controls (68.74 ± 8.28 years old, 55% female), 15 Aß-negative MCI patients (MCI-n) (68.87 ± 8.83 years old, 60% female), 29 Aß-positive MCI patients (MCI-p) (73.03 ± 7.05 years old, 52% female), and 29 Aß-positive AD patients (72.93 ± 9.11 years old, 55% female). FIELD STRENGTH/SEQUENCE: 3.0T; DTI, T1 -weighted, T2 -weighted, T2 star-weighted angiography, and Aß PET (18 F-florbetaben or 11 C-PIB). ASSESSMENT: FW-corrected and standard diffusion indices were analyzed using trace-based spatial statistics. Area under the curve (AUC) in distinguishing MCI subtypes were compared using support vector machine (SVM). STATISTICAL TESTS: Chi-squared test, one-way analysis of covariance, general linear regression analyses, nonparametric permutation tests, partial Pearson's correlation, receiver operating characteristic curve analysis, and linear SVM. A P value <0.05 was considered statistically significant. RESULTS: Compared with CH/MCI-n/MCI-p, AD showed significant change in tissue compartment indices of FW-DTI. No difference was found in the FW index among pair-wise group comparisons (the minimum FWE-corrected P = 0.114). There was a significant association between FW-DTI indices and memory and visuospatial function. The SVM classifier with tissue radial diffusivity as an input feature had the best classification performance of MCI subtypes (AUC = 0.91), and the classifying accuracy of FW-DTI was all over 89.89%. DATA CONCLUSION: FW-DTI indices prove to be potential biomarkers of AD. The classification of MCI subtypes based on SVM and FW-DTI indices has good accuracy and could help early diagnosis. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Down-regulated TINAGL1 in fibroblasts impairs wound healing in diabetes.

Matricellular proteins, a group of extracellular matrix (ECM) proteins, are key regulators of skin repair and their dysregulation impairs wound healing in diabetes. Tubulointerstitial nephritis antigen like 1 (TINAGL1) is a new member of matricellular protein family, and the understanding of its functional role is still relatively limited. In the current study, we detected the expression of TINAGL1 in diabetic skin wound tissues through RT-PCR, ELISA and Western blot analysis, investigated the contribution of TINAGL1 to wound healing through cutaneous administration of recombinant TINAGL1 protein, and characterized its regulation by hyperglycemia through RNA-seq and signal pathway inhibition assay. We showed that TINAGL1 expression has dynamic change and reaching a peak on day-9 after wound during the wound healing process in wild-type (WT) mice. Interestingly, decreased TINAGL1 expression is detected in skin tissues of diabetic patients and mice after wound. Then, we found that high glucose (HG), an important factor that impairs wound healing, reduces the expression of TINAGL1 in fibroblasts through JNK pathway. Notably, the histology analysis, Masson trichrome assay and IHC assay showed that exogenous TINAGL1 promotes wound healing in diabetic mice by accelerating the formation of granulation tissues. Our study provides evidence that TINAGL1 has an essential role in diabetic wound healing, and meanwhile, indicates that manipulation of TINAGL1 might be a possible therapeutic approach.

Retrospective Study of Lower Respiratory Tract Infections in the Intensive Care Unit Detected by the FilmArray Pneumonia Panel.

BACKGROUND: Lower respiratory tract infections (LRIs) are an important public health concern and a leading cause of death from infection worldwide. The current study aims to evaluate the distribution of viral and bacterial pathogens in lower respiratory tract specimens. METHODS: Between April 2022 and December 2022, specimens from lower respiratory tract from patients aged between 37 and 85 years in an intensive care unit (ICU) of Asia University Hospital were analysed by the FilmArrayTM pneumonia panel (PP) assay. RESULTS: There were 54 patients for whom the FilmArrayTM PP assay was analysed, and 25 (46.3%) of them showed positive results. Among the 54 specimens, 12 (22.2%, 12/54) had a single pathogen, 13 (24.1%, 13/54) had multiple pathogens, and 29 (53.7%, 29/54) had no pathogens. The overall positive rate of the specimens was 46.3% (25/54). CONCLUSIONS: The FilmArrayTM PP assay may act as a feasible diagnostic tool for LRIs in ICUs.

A pH-responsive metal-organic framework for the co-delivery of HIF-2α siRNA and curcumin for enhanced therapy of osteoarthritis.

The occurrence of osteoarthritis (OA) is highly correlated with the reduction of joint lubrication performance, in which persistent excessive inflammation and irreversible destruction of cartilage dominate the mechanism. The inadequate response to monotherapy methods, suboptimal efficacy caused by undesirable bioavailability, short retention, and lack of stimulus-responsiveness, are few unresolved issues. Herein, we report a pH-responsive metal-organic framework (MOF), namely, MIL-101-NH2, for the co-delivery of anti-inflammatory drug curcumin (CCM) and small interfering RNA (siRNA) for hypoxia inducible factor (HIF-2α). CCM and siRNA were loaded via encapsulation and surface coordination ability of MIL-101-NH2. Our vitro tests showed that MIL-101-NH2 protected siRNA from nuclease degradation by lysosomal escape. The pH-responsive MIL-101-NH2 gradually collapsed in an acidic OA microenvironment to release the CCM payloads to down-regulate the level of pro-inflammatory cytokines, and to release the siRNA payloads to cleave the target HIF-2α mRNA for gene-silencing therapy, ultimately exhibiting the synergetic therapeutic efficacy by silencing HIF-2α genes accompanied by inhibiting the inflammation response and cartilage degeneration of OA. The hybrid material reported herein exhibited promising potential performance for OA therapy as supported by both in vitro and in vivo studies and may offer an efficacious therapeutic strategy for OA utilizing MOFs as host materials.

Research progress and hot spot analysis related to oxidative stress and osteoarthritis: a bibliometric analysis.

BACKGROUND: Osteoarthritis, a common degenerative osteochondral disease, has a close relationship between its mechanism of occurrence and oxidative stress. However, there are relatively few relevant studies in this field, and a more mature research system has not yet been formed. METHODS: By searching the Web of Science (WOS) database, we obtained 1 412 publications in the field of osteoarthritis and oxidative stress. The search results were then analyzed bibliometrically using Citespace and VOSviewer, including a study of publication trends in the field, analysis of core authors, analysis of countries and institutions with high contributions, analysis of core journals, and to identify research trends and hot spots in the field, we performed keyword clustering. RESULTS: We collected 1 412 publications on the field of osteoarthritis and oxidative stress from 1998-2022. By analyzing the publication trends in the field, we noted an exponential increase in the number of publications per year since 2014. We then identified the core authors in the field (Blanco, Francisco J., Loeser, Richard F., Vaamonde-garcia, et.al) as well as the countries (China, USA, Italy et.al) and institutions (Xi An Jiao Tong Univ, Wenzhou Med Univ, Zhejiang Univ et.al). The OSTEOARTHRITIS AND CARTILAGE and INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES contain a large number of research papers in this field, and through keyword co-occurrence analysis, we counted 3 227 keywords appearing in the field of osteoarthritis and oxidative stress. These keywords were clustered into 9 groups, representing 9 different research hotspots. CONCLUSIONS: Research in the field of osteoarthritis and oxidative stress has been developing since 1998 and is now maturing, but there is an urgent need to strengthen international academic exchanges and discuss the future focus of research development in the field of osteoarthritis and oxidative stress.

Expression Pattern of ALOXE3 in Mouse Brain Suggests Its Relationship with Seizure Susceptibility.

Arachidonic acid (AA), a polyunsaturated fatty acid, is involved in the modulation of neuronal excitability in the brain. Arachidonate lipoxygenase 3 (ALOXE3), a critical enzyme in the AA metabolic pathway, catalyzes the derivate of AA into hepoxilins. However, the expression pattern of ALOXE3 and its role in the brain has not been described until now. Here we showed that the levels of Aloxe3 mRNA and protein kept increasing since birth and reached the highest level at postnatal day 30 in the mouse hippocampus and temporal cortex. Histomorphological analyses indicated that ALOXE3 was enriched in adult hippocampus, somatosensory cortex and striatum. The distribution was restricted to the neurites of function-specific subregions, such as mossy fibre connecting hilus and CA3 neurons, termini of Schaffer collateral projections, and the layers III and IV of somatosensory cortex. The spatiotemporal expression pattern of ALOXE3 suggests its potential role in the modulation of neural excitability and seizure susceptibility. In fact, decreased expression of ALOXE3 and elevated concentration of AA in the hippocampus was found after status epilepticus (SE) induced by pilocarpine. Local overexpression of ALOXE3 via adeno-associated virus gene transfer restored the elevated AA level induced by SE, alleviated seizure severities by increasing the latencies to myclonic switch, clonic convulsions and tonic hindlimb extensions, and decreased the mortality rate in the pilocarpine-induced SE model. These results suggest that the expression of ALOXE3 is a crucial regulator of AA metabolism in brain, and potentially acts as a regulator of neural excitability, thereby controlling brain development and seizure susceptibility.

Hesperetin derivative decreases CCl4 -induced hepatic fibrosis by Ptch1-dependent mechanisms.

Hepatic fibrosis (HF), a continuous wound-healing response of the liver to repeated injuries, is characterized by abnormal extracellular matrix (ECM) accumulation. Hepatic stellate cells (HSCs) are considered a major cell type for ECM production. However, recent evidence indicates the lack of effective treatments for HF. Hesperetin, a Traditional Chinese Medicine monomer, has been isolated from the fruit peel of Citrusaurantium L. (Rutaceae). Growing evidence suggests the partial function of hesperetin in HF treatment. A hesperetin derivative (HD) was synthesized in our laboratory to increase the bioavailability and the water solubility of hesperetin. In this study, we detected the functions of HD in a mouse model of CCl4 -induced HF and transforming growth factor-ß1-stimulated HSC-T6 cells, in vivo and in vitro. HD reduced histological damage and CCl4 -induced HF. Moreover, HD interference was associated with the activation of indicators in HSC-T6 cells, showing that HD is involved in HSCs activation in HF. Mechanistically, the Hedgehog pathway is involved in the HD treatment of HF, and HD may attenuate the aberrant expression of patched1. In conclusion, the studies indicate that HD may function as a potential antifibrotic Traditional Chinese Medicine monomer in HF therapy.

Interaction between hepatokines and metabolic diseases.

Metabolic diseases are broadly defined as diseases caused by problems in metabolic function, including central obesity, insulin resistance, lipid glucose abnormalities, and elevated blood pressure. As an important metabolic organ, the liver plays a key role in regulating many physiological processes such as systemic glucose and lipid metabolism. Numerous studies in recent years have shown that the liver can synthesize and secrete a variety of hepatokines, including FGF21, Fetuin-A and ANGPTL8, which regulate the metabolism in an autocrine/paracrine manner. Intervention of hepatokines expression may contribute to the prevention, diagnosis and treatment of metabolic diseases. However, further studies are needed to be investigated as the mechanism of hepatokines and metabolic homeostasis is still elusive. In this review, we summarize the relationships between hepatokines and metabolic diseases in order to provide new strategies for the treatment of metabolic diseases.

Functional assessment of cryopreserved clinical grade hESC-RPE cells as a qualified cell source for stem cell therapy of retinal degenerative diseases.

The biosafety and efficiency of transplanting retinal pigment epithelial (RPE) cells derived from both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have been evaluated in phase I and phase II clinical trials. For further large-scale application, cryopreserved RPE cells must be used; thus, it is highly important to investigate the influence of cryopreservation and thawing on the biological characteristics of hESC-RPE cells and their post-transplantation vision-restoring function. Here, via immunofluorescence, qPCR, transmission electron microscopy, transepithelial electrical resistance, and enzyme-linked immunosorbent assays (ELISAs), we showed that cryopreserved hESC-RPE cells retained the specific gene expression profile, morphology, ultrastructure, and maturity-related functions of induced RPE cells. Additionally, cryopreserved hESC-RPE cells exhibited a polarized monolayer, tight junction, and gap junction structure and an in vitro nanoparticle phagocytosis capability similar to those of induced hESC-RPE cells. However, the level of pigment epithelium-derived factor (PEDF) secretion was significantly decreased in cryopreserved hESC-RPE cells. Royal College of Surgeons rats with cryopreserved hESC-RPE cells engrafted into the subretinal space exhibited a significant decrease in the b-wave amplitude compared with rats engrafted with induced hESC-RPE cells at 4 weeks post transplantation. However, the difference disappeared at 8 weeks and 12 weeks post operation. No significant difference in the outer nuclear layer (ONL) thickness was observed between the two groups. Our data showed that even after cryopreservation and thawing, cryopreserved hESC-RPE cells are still qualified as a donor cell source for cell-based therapy of retinal degenerative diseases.

Valproate-Induced Epigenetic Upregulation of Hypothalamic Fto Expression Potentially Linked with Weight Gain.

Valproate (VPA), a widely-used antiepileptic drug, is a selective inhibitor of histone deacetylase (HDAC) that play important roles in epigenetic regulation. The patient with different diseases receiving this drug tend to exhibit weight gain and abnormal metabolic phenotypes, but the underlying mechanisms remain largely unknown. Here we show that VPA increases the Fto mRNA and protein expression in mouse hypothalamic GT1-7 cells. Interestingly, VPA promotes histone H3/H4 acetylation and the FTO expression which could be reversed by C646, an inhibitor for histone acetyltransferase. Furthermore, VPA weakens the FTO's binding and enhances the binding of transcription factor TAF1 to the Fto promoter, and C646 leads to reverse effect of the VPA, suggesting an involvement of the dynamic of histone H3/H4 acetylation in the regulation of FTO expression. In addition, the mice exhibit an increase in the food intake and body weight at the beginning of 2-week treatment with VPA. Simultaneously, in the hypothalamus of the VPA-treated mice, the FTO expression is upregulated and the H3/H4 acetylation is increased; further the FTO's binding to the Fto promoter is decreased and the TAF1's binding to the promoter is enhanced, suggesting that VPA promotes the assembly of the basal transcriptional machinery of the Fto gene. Finally, the inhibitor C646 could restore the effects of VPA on FTO expression, H3/H4 acetylation, body weight, and food intake; and loss of FTO could reverse the VPA-induced increase of body weight and food intake. Taken together, this study suggests an involvement of VPA in the epigenetic upregulation of hypothalamic FTO expression that is potentially associated with the VPA-induced weight gain.

Rapid Cobas Liat SARS-CoV-2 Assay in Comparison with the Laboratory-Developed Real-Time RT-PCR Test.

BACKGROUND: The objective of this study was to compare the validity of two different assays for the detection of SARS-CoV-2. METHODS: We collected 50 nasopharyngeal swabs in universal transport medium from the emergency department of Asia University Hospital for the detection of SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR). The samples for the Liat SARS-CoV-2 influenza A/B test were stored at -70℃ after SARS-CoV-2 testing using the RT-PCR in order to assess method comparison. RESULTS: In this study, the Limit of detection (LOD) of the cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test is 12 copies/µL and the assay obtained 100% positive agreement and negative percent agreement with RT-PCR. CONCLUSIONS: In summary, a prefect agreement exists between the detection of SARS-CoV-2 conducted with the cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test and the RT-PCR. The cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test is a reliable method for the detection of SARS-CoV-2, and it only requires 20 minutes to obtain the results. On the other hand, the cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test is accurate, easy to use, and provides a faster turnaround time than testing performed in the high-throughput platform.

Comparison of Manual and Automated Nucleic Acid Extraction Methods in Virus Transport Medium.

BACKGROUND: The implementation of an automated nucleic acid extraction system has many advantages over the manual methods. The purpose of this study was to evaluate the validity of two different methods for nucleic acid extraction in virus transport medium. METHODS: We collected 20 nasopharyngeal swabs in viral transport medium from the emergency department of the Asia University Hospital for the detection of SARS-CoV-2. The performance of the MaelstromTM 8 (Taiwan Advanced Nanotech) and the QIAamp Viral RNA Mini Kit (Qiagen) were compared for the extraction of nucleic acid from viral transport medium. The extracts were used for the validation of the RNA extraction procedures. The RNase P target was amplified in a one-step reverse transcription-quantitative PCR (RT-qPCR) reaction, as internal control for the extraction method. RESULTS: In this study, the agreement between the two methods was good and Pearson's correlation coefficient (r) was 0.919 (p < 0.001). The mean cycle threshold value of the two methods was 29.1. CONCLUSIONS: Overall, the performance values of the MaelstromTM 8 and the QIAamp Viral RNA Mini Kit were comparable to each other. In summary, the MaelstromTM 8 provides a standardized procedure, avoidance of sample-to-sample cross contaminations, is easy to use, improves turnaround time and requires less hands-on time as compared to the manual extraction method. The MaelstromTM 8 is more suitable for clinical laboratories that carry small or medium-sized samples for nucleic acid extraction.

Analytical Performance of the VIDAS® BRAHMS Procalcitonin Assay and Beckman Coulter Unicel® DXI Procalcitonin Assay in a Stat Laboratory.

BACKGROUND: The objective of this study was to compare the validity of two different procalcitonin assays. METHODS: We collected 63 plasma samples from a stat laboratory. The plasma values of procalcitonin ranged from 0.01 to 98.1 µg/L when tested on the Access® platform and from < 0.05 to 98.5 µg/L when tested on the VIDAS® platform. The patients included 28 females ranging in age from 8 to 98 years of age (68 ± 22.6 years) and 35 males ranging in age from 35 to 90 years of age (69.2 ± 13.4 years). RESULTS: In this study, the agreement between the two methods was good and Pearson's correlation coefficient (r) was 0.989 (p < 0.001). CONCLUSIONS: In summary, a high correlation exists between quantitative procalcitonin measurements conducted with the VIDAS® BRAHMS and the Beckman Coulter Unicel® DXI assays. The VIDAS® BRAHMS procalcitonin assay is a reliable method for determining the levels of procalcitonin in plasma, but requires manual operation, hands-on technical expertise, and time. On the other hand, the Beckman Coulter Unicel® DXI assay is fully automated and may increase laboratory efficiency, and reduce the overall turnaround time.

Ebselen alleviates testicular pathology in mice with Zika virus infection and prevents its sexual transmission.

Despite the low case fatality, Zika virus (ZIKV) infection has been associated with microcephaly in infants and Guillain-Barré syndrome. Antiviral and vaccine developments against ZIKV are still ongoing; therefore, in the meantime, preventing the disease transmission is critical. Primarily transmitted by Aedes species mosquitoes, ZIKV also can be sexually transmitted. We used AG129 mice lacking interferon-α/ß and -γ receptors to study the testicular pathogenesis and sexual transmission of ZIKV. Infection of ZIKV progressively damaged mouse testes, increased testicular oxidative stress as indicated by the levels of reactive oxygen species, nitric oxide, glutathione peroxidase 4, spermatogenesis-associated-18 homolog in sperm and pro-inflammatory cytokines including IL-1ß, IL-6, and G-CSF. We then evaluated the potential role of the antioxidant ebselen (EBS) in alleviating the testicular pathology with ZIKV infection. EBS treatment significantly reduced ZIKV-induced testicular oxidative stress, leucocyte infiltration and production of pro-inflammatory response. Furthermore, it improved testicular pathology and prevented the sexual transmission of ZIKV in a male-to-female mouse sperm transfer model. EBS is currently in clinical trials for various diseases. ZIKV infection could be on the list for potential use of EBS, for alleviating the testicular pathogenesis with ZIKV infection and preventing its sexual transmission.

A case of cutaneous pseudolymphoma with a distinctive appearance treated successfully by intralesional interferon alpha-1b and corticosteroids.

Cutaneous pseudolymphoma (CPL) encompasses various forms of benign lymphocytic proliferative dermatoses that mimic the clinical and/or pathological changes of lymphoma. The clinical manifestations of CPL vary due to differences in the pathogenesis, and accordingly, no specific treatment has been identified. Here, we report a case of CPL on the nose, which had a distinctive appearance and was treated successfully using a combination of intralesional interferon alpha-1b and compound betamethasone (betamethasone sodium phosphate and betamethasone dipropionate). This combination may be a good option for localized CPLs at particular anatomical sites.

[Research progresses on PGC-1α, a key energy metabolic regulator].

Disturbance of the energy balance, when the energy intake exceeds its expenditure, is a major risk factor for the development of metabolic syndrome (MS). The peroxisome proliferator activated receptor γ (PPARγ) coactivator-1α (PGC-1α) functions as a key regulator of energy metabolism and has become a hotspot in current researches. PGC-1α sensitively responds to the environmental stimuli and nutrient signals, and further selectively binds to different transcription factors to regulate various physiological processes, including glucose metabolism, lipid metabolism, and circadian clock. In this review, we described the gene and protein structure of PGC-1α, and reviewed its tissue-specific function in the regulation of energy homeostasis in various mammalian metabolic organs, including liver, skeletal muscle and heart, etc. At the meanwhile, we summarized the application of potential small molecule compounds targeting PGC-1α in the treatment of metabolic diseases. This review will provide theoretical basis and potential drug targets for the treatment of metabolic diseases.

Epidemiologic relationship between periodontitis and type 2 diabetes mellitus.

BACKGROUND: To systematically review the epidemiologic relationship between periodontitis and type 2 diabetes mellitus (T2DM). METHODS: Four electronic databases were searched up until December 2018. The manual search included the reference lists of the included studies and relevant journals. Observational studies evaluating the relationship between T2DM and periodontitis were included. Meta-analyses were conducted using STATA. RESULTS: A total of 53 observational studies were included. The Adjusted T2DM prevalence was significantly higher in periodontitis patients (OR = 4.04, p = 0.000), and vice versa (OR = 1.58, p = 0.000). T2DM patients had significantly worse periodontal status, as reflected in a 0.61 mm deeper periodontal pocket, a 0.89 mm higher attachment loss and approximately 2 more lost teeth (all p = 0.000), than those without T2DM. The results of the cohort studies found that T2DM could elevate the risk of developing periodontitis by 34% (p = 0.002). The glycemic control of T2DM patients might result in different periodontitis outcomes. Severe periodontitis increased the incidence of T2DM by 53% (p = 0.000), and this result was stable. In contrast, the impact of mild periodontitis on T2DM incidence (RR = 1.28, p = 0.007) was less robust. CONCLUSIONS: There is an evident bidirectional relationship between T2DM and periodontitis. Further well-designed cohort studies are needed to confirm this finding. Our results suggest that both dentists and physicians need to be aware of the strong connection between periodontitis and T2DM. Controlling these two diseases might help prevent each other's incidence.