PKCδ regulates the vascular biology in diabetic atherosclerosis.

Diabetes mellitus, known for its complications, especially vascular complications, is becoming a globally serious social problem. Atherosclerosis has been recognized as a common vascular complication mechanism in diabetes. The diacylglycerol (DAG)-protein kinase C (PKC) pathway plays an important role in atherosclerosis. PKCs can be divided into three subgroups: conventional PKCs (cPKCs), novel PKCs (nPKCs), and atypical PKCs (aPKCs). The aim of this review is to provide a comprehensive overview of the role of the PKCδ pathway, an isoform of nPKC, in regulating the function of endothelial cells, vascular smooth muscle cells, and macrophages in diabetic atherosclerosis. In addition, potential therapeutic targets regarding the PKCδ pathway are summarized. Video Abstract.

The Role of TGF-ß Signaling in Saphenous Vein Graft Failure after Peripheral Arterial Disease Bypass Surgery.

Saphenous vein bypass grafting is an effective technique used to treat peripheral arterial disease (PAD). However, restenosis is the major clinical challenge for the graft vessel among people with PAD postoperation. We hypothesize that there is a common culprit behind arterial occlusion and graft restenosis. To investigate this hypothesis, we found TGF-ß, a gene specifically upregulated in PAD arteries, by bioinformatics analysis. TGF-ß has a wide range of biological activities and plays an important role in vascular remodeling. We discuss the molecular pathway of TGF-ß and elucidate its mechanism in vascular remodeling and intimal hyperplasia, including EMT, extracellular matrix deposition, and fibrosis, which are the important pathways contributing to stenosis. Additionally, we present a case report of a patient with graft restenosis linked to the TGF-ß pathway. Finally, we discuss the potential applications of targeting the TGF-ß pathway in the clinic to improve the long-term patency of vein grafts.

Cervical vagal nerve schwannoma induced arrhythmia: a rare case report and literature review.

BACKGROUND: Schwannomas are benign tumors deriving from the sheath of cranial and peripheral nerves. The vagus nerve is comprised of a complex neuro-endocrine-immune network that maintains homeostasis, most tracts of it play a role in parasympathetic activity. We present an example of a rare cervical vagal schwannoma case accompanied by arrhythmia. CASE PRESENTATION: A 35-year-old female patient with a left cervical vagus schwannoma and ventricular arrhythmia underwent schwannoma resection in the operating room. The patient's suppressed heart rate increased after tumor removal, and the cardiac rhythm returned to normal postoperatively. Pathological examination demonstrated the diagnosis of schwannoma. CONCLUSIONS: This case explains the link between the vagus nerve and the cardiovascular system, proving that a damaged cervical vagus nerve can inhibit the heart rate and lead to arrhythmias, and eventually requiring surgical intervention.

The Anatomy of the Temporal and Zygomatic Branches of the Facial Nerve: Application to Crow's Feet Wrinkles.

BACKGROUND: Advances in the understanding of wrinkling crow's feet while improving the safety and efficacy of botulinum toxin type A injection has pointed to drug dispersion in the lateral orbital wrinkles as a cause of adverse events of botulinum toxin type A injection. The purpose of this study is to identify the distribution of temporal and zygomatic branches of facial nerve in the orbicularis oculi muscles. METHODS: Anatomical dissection of cadavers was performed in 31 cadavers, 13 females and 18 males, with ages ranging from 20 to 60 years, which of all had been embalmed by 10% formalin solution. The facial nerve was identified within subcutaneous tissue close periorbital region and both traced proximal and distal. Its temporal branch, zygomatic branch, facial and muscular entrance were located and accurately measured relative to established surface landmarks. RESULTS: Dissection of the facial nerve revealed 2 to 6 entrances of the temporal branch into the orbicularis oculi and 1 to 5 entrances of the zygomatic branch into the orbicularis oculi. Concerning the measurements of neural entering points, distance and angle from orbicularis oculi muscle to lateral ocular angle, a distribution map of its muscular entrance and their patterns of distribution were constructed. According to the dense area of the coordinate map, there were 3 points determined as the muscular entrance points to established surface landmarks. CONCLUSIONS: An anatomical dissection of cadavers was performed to identify the distribution of temporal and zygomatic branches of the facial nerve in the orbicularis oculi. According to the dense area of the coordinate map, the surface landmarks of 3 points were established as the muscular entrance of the facial nerve (MEF).

Expression Changes of NMDA and AMPA Receptor Subunits in the Hippocampus in rats with Diabetes Induced by Streptozotocin Coupled with Memory Impairment.

Cognitive impairment in diabetes (CID) is a severe chronic complication of diabetes mellitus (DM). It has been hypothesized that diabetes can lead to cognitive dysfunction due to expression changes of excitatory neurotransmission mediated by N-methyl-D-aspartate receptors (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR); however, the pathogenesis involved in this has not been fully understood, especially at early phase of DM. Here, we sought to determine the cognitive changes and aim to correlate this with the expression changes of NMDAR and AMPAR of glutamate signaling pathways in the rat hippocampus from early phase of DM and in the course of the disease progression. By Western blot analysis and immunofluorescence labeling, the hippocampus in diabetic rats showed a significant increase in protein expression NMDAR subunits NR1, NR2A and NR2B and AMPAR subunit GluR1. Along with this, behavioral test by Morris water maze showed a significant decline in their performance when compared with the control rats. It is suggested that NR1, NR2A, NR2B and GluR1are involved in learning and memory and that their expression alterations maybe correlated with the occurrence and development of CID in diabetic rats induced by streptozotocin.

An Anatomic Study of the Keyhole Supra-Tentorium to Infra-Tentorium Endoscope Approach.

To provide anatomic basis for the retrosigmoid supra-tentorium to infra-tentorium keyhole approach and to explore the feasibility, 60 skulls were observed and measured to demonstrate the position relations among related bony landmarks, 12 cadaveric heads were dissected and measured for localization of the keyhole and the incision through tentorium. For giving the angle and depth for endoscopic approach, 40 adult volunteers were performed head MRI scan and the pictures were measured and analyzed. The surface projection of sigmoid and transverse sinus can be positioned by mastoidale, external occipital protuberance, and anterior end of parietomastoid suture (AEPMS) on body. There is a safe trigone of cerebellar tentorium (STCT) among inner edge of upper curve of sigmoid sinus, entrance of tentorial sinus/vein and midpoint of posterior edge of temporal arcuate eminence. 15 mm superior to the midpoint between asterion and AEPMS can be recognized as the central point of the keyhole. Magnetic resonance imaging pictures show there is potential subarachnoid space for endoscopic approach from the indicated keyhole to pontocerebellar trigone. This study demonstrated endoscopy can arrive at pontocerebellar trigone through the STCT and the keyhole supra-tentorium to infra-tentorium endoscope approach is feasible in anatomy and will contribute to excise lesions involving both supra- and infra-tentorial structures.

Local knockdown of Nav1.6 relieves pain behaviors induced by BmK I.

Voltage-gated sodium channels (VGSCs) in peripheral nociceptive sensory neurons are critical to transmit pain signals. BmK I purified from the venom of scorpion Buthus martensi Karsch (BmK) has been demonstrated to be the primary contributor of envenomation-associated pain. However, the role of distinct VGSCs such as Nav1.6 in the induction and maintenance of pain behaviors induced by BmK I was ambiguous. Herein, using molecular and behavioral approaches we investigated the mRNA and protein expression profiles of Nav1.6 in rat DRG after intraplantar injection of BmK I and tested the pain behaviors after knockdown of Nav1.6 in BmK I-treated rats. It was shown that during induction and maintenance of pain responses induced by BmK I, the expression of Nav1.6 in DRG was found to be significantly increased at both mRNA and protein levels. The percentage of co-localization of Nav1.6 and Isolectin B4, a molecular marker of small diameter non-peptidergic DRG neurons, was increased at the maintenance phase of pain responses. Furthermore, spontaneous pain and mechanical allodynia, but not thermal hyperalgesia induced by BmK I, were significantly alleviated after knockdown of Nav1.6. These data strongly suggest that Nav1.6 plays an indispensable role in the peripheral pain hypersensitivity induced by BmK I.

Functional up-regulation of Nav1.8 sodium channel on dorsal root ganglia neurons contributes to the induction of scorpion sting pain.

BmK I, purified from the venom of scorpion Buthus martensi Karsch (BmK), is a receptor site-3-specific modulator of voltage-gated sodium channels (VGSCs) and can induce pain-related behaviors in rats. The tetrodotoxin-resistant (TTX-R) sodium channel Nav1.8 contributes to most of the sodium current underlying the action potential upstroke in dorsal root ganglia (DRG) neurons and may serve as a critical ion channel targeted by BmK I. Herein, using electrophysiological, molecular, and behavioral approaches, we investigated whether the aberrant expression of Nav1.8 in DRG contributes to generation of pain induced by BmK I. The expression of Nav1.8 was found to be significantly increased at both mRNA and protein levels following intraplantar injection of BmK I in rats. In addition, the current density of TTX-R Nav1.8 sodium channel is significantly increased and the gating kinetics of Nav1.8 is also altered in DRG neurons from BmK I-treated rats. Furthermore, spontaneous pain and mechanical allodynia, but not thermal hyperalgesia induced by BmK I, are significantly alleviated through either blockade of the Nav1.8 sodium channel by its selective blocker A-803467 or knockdown of the Nav1.8 expression in DRG by antisense oligodeoxynucleotide (AS-ODN) targeting Nav1.8 in rats. Finally, BmK I was shown to induce enhanced pain behaviors in complete freund's adjuvant (CFA)-inflamed rats, which was partly due to the over-expression of Nav1.8 in DRG. Our results suggest that functional up-regulation of Nav1.8 channel on DRG neurons contributes to the development of BmK I-induced pain in rats.

Brain natriuretic peptide suppresses pain induced by BmK I, a sodium channel-specific modulator, in rats.

BACKGROUND: A previous study found that brain natriuretic peptide (BNP) inhibited inflammatory pain via activating its receptor natriuretic peptide receptor A (NPRA) in nociceptive sensory neurons. A recent study found that functional NPRA is expressed in almost all the trigeminal ganglion (TG) neurons at membrane level suggesting a potentially important role for BNP in migraine pathophysiology. METHODS: An inflammatory pain model was produced by subcutaneous injection of BmK I, a sodium channel-specific modulator from venom of Chinese scorpion Buthus martensi Karsch. Quantitative PCR, Western Blot, and immunohistochemistry were used to detect mRNA and protein expression of BNP and NPRA in dorsal root ganglion (DRG) and dorsal horn of spinal cord. Whole-cell patch clamping experiments were conducted to record large-conductance Ca2+-activated K+ (BKCa) currents of membrane excitability of DRG neurons. Spontaneous and evoked pain behaviors were examined. RESULTS: The mRNA and protein expression of BNP and NPRA was up-regulated in DRG and dorsal horn of spinal cord after BmK I injection. The BNP and NPRA was preferentially expressed in small-sized DRG neurons among which BNP was expressed in both CGRP-positive and IB4-positive neurons while NPRA was preferentially expressed in CGRP-positive neurons. BNP increased the open probability of BKCa channels and suppressed the membrane excitability of small-sized DRG neurons. Intrathecal injection of BNP significantly inhibited BmK-induced pain behaviors including both spontaneous and evoked pain behaviors. CONCLUSIONS: These results suggested that BNP might play an important role as an endogenous pain reliever in BmK I-induced inflammatory pain condition. It is also suggested that BNP might play a similar role in other pathophysiological pain conditions including migraine.

Association Study of Pleural Mesothelioma and Oncogenic Simian Virus 40 in the Crocidolite-Contaminated Area of Dayao County, Yunnan Province, Southwest China.

Background: In Dayao County, Chuxiong Yi Autonomous Prefecture, Yunnan Province, Southwest China, 5% of the surface is scattered with blue asbestos, which has a high incidence of pleural mesothelioma (PMe). Simian virus 40 (SV40) is a small circular double-stranded DNA polyomavirus that can cause malignant transformation of normal cells of various human and animal tissue types and promote tumor growth. In this study, we investigate whether oncogenic SV40 is associated with the occurrence of PMe in the crocidolite-contaminated area of Dayao County, Yunnan Province, Southwest China. Methods: Tumor tissues from 51 patients with PMe (40 of whom had a history of asbestos exposure) and pleural tissues from 12 non-PMe patients (including diseases such as pulmonary maculopathy and pulmonary tuberculosis) were collected. Three pairs of low-contamination risk primers (SVINT, SVfor2, and SVTA1) were used to detect the gene fragment of SV40 large T antigen (T-Ag) by polymerase chain reaction (PCR). The presence of SV40 T-Ag in PMe tumor tissues and PMe cell lines was detected by Western blotting and immunohistochemical staining with SV40-related antibodies (PAb 101 and PAb 416). Results: PCR, Western blotting, and immunohistochemical staining results showed that the Met5A cell line was positive for SV40 and contained the SV40 T-Ag gene and protein. In contrast, the various PMe cell lines NCI-H28, NCI-H2052, and NCI-H2452 were negative for SV40. PCR was negative for all three sets of low-contamination risk primers in 12 non-PMe tissues and 51 PMe tissues. SV40 T-Ag was not detected in 12 non-PMe tissues or 51 PMe tissues by immunohistochemical staining. Conclusion: Our data suggest that the occurrence of PMe in the crocidolite-contaminated area of Yunnan Province may not be related to SV40 infection and that crocidolite exposure may be the main cause of PMe. The Clinical Trial Registration number: 2020-YXLL20.

Synaptotagmins family affect glucose transport in retinal pigment epithelial cells through their ubiquitination-mediated degradation and glucose transporter-1 regulation.

BACKGROUND: Synaptotagmins (SYTs) are a family of 17 membrane transporters that function as calcium ion sensors during the release of Ca2+-dependent neurotransmitters and hormones. However, few studies have reported whether members of the SYT family play a role in glucose uptake in diabetic retinopathy (DR) through Ca2+/glucose transporter-1 (GLUT1) and the possible regulatory mechanism of SYTs. AIM: To elucidate the role of the SYT family in the regulation of glucose transport in retinal pigment epithelial cells and explore its potential as a therapeutic target for the clinical management of DR. METHODS: DR was induced by streptozotocin in C57BL/6J mice and by high glucose medium in human retinal pigment epithelial cells (ARPE-19). Bioinformatics analysis, reverse transcriptase-polymerase chain reaction, Western blot, flow cytometry, ELISA, HE staining, and TUNEL staining were used for analysis. RESULTS: Six differentially expressed proteins (SYT2, SYT3, SYT4, SYT7, SYT11, and SYT13) were found between the DR and control groups, and SYT4 was highly expressed. Hyperglycemia induces SYT4 overexpression, manipulates Ca2+ influx to induce GLUT1 fusion with the plasma membrane, promotes abnormal expression of the glucose transporter GLUT1 and excessive glucose uptake, induces ARPE-19 cell apoptosis, and promotes DR progression. Parkin deficiency inhibits the proteasomal degradation of SYT4 in DR, resulting in SYT4 accumulation and enhanced GLUT1 fusion with the plasma membrane, and these effects were blocked by oe-Parkin treatment. Moreover, dysregulation of the myelin transcription factor 1 (Myt1)-induced transcription of SYT4 in DR further activated the SYT4-mediated stimulus-secretion coupling process, and this process was inhibited in the oe-MYT1-treated group. CONCLUSION: Our study reveals the key role of SYT4 in regulating glucose transport in retinal pigment epithelial cells during the pathogenesis of DR and the underlying mechanism and suggests potential therapeutic targets for clinical DR.

Posttraumatic arteriovenous fistula of the lower extremity and the pathological characteristic-case series and literature review.

The clinical presentation, treatment history, and outcomes of two patients with posttraumatic arteriovenous fistula (PTAVF) were analyzed and compared with the pathological tissues of patients with hemodialysis arteriovenous fistula (HAVF). A search of the biomedical literature database (PubMed), using the keywords " lower extremity" and "PTAVF," was conducted to obtain results and review the data. Postoperative histological analysis of patients with PTAVF showed differences from that of HAVF. The literature screening and analysis revealed that PTAVF is a chronic progressive process, with 70% of patients diagnosed after 3 months. The choice of treatment revealed that 20% of patients had severe complications and all were treated endovascularly. Due to the abnormal fistula of PTAVF and its specific histopathological features, the disease is not self-limiting. It is unwise to wait for PTAVF to cause "failure." We recommend early and timely cure of this disease by surgery to avoid serious complications.

Impaired dendritic cell maturation and IL-10 production following H. pylori stimulation in gastric cancer patients.

The current study was to investigate the interaction between Helicobacter pylori and human dendritic cells (DCs). Whether impaired DC function can influence the outcome of H. pylori infections. Human monocyte-derived DCs (MDDCs) from five gastric cancer patients and nine healthy controls were stimulated with H. pylori. Maturation markers of MDDC were examined by flow cytometry. IL-10 and TNF-α released by MDDCs and IL-17 produced by T cells were measured by ELISA. Regulatory signaling pathways of IL-10 were examined by ELISA, western blotting, and chromatin immunoprecipitation assay. The results showed that as compared with healthy individuals, the maturation marker CD40 in MDDCs, IL-17A expression from T cells, and IL-10 expression from MDDCs were significantly lower in gastric cancer patients. Blocking DC-SIGN, TLR2, and TLR4 could reverse H. pylori-associated IL-10 production. Activation of the p38 MAPK and NF-kB signaling pathways concomitant with decreased tri-methylated H3K9 and increased acetylated H3 accounted for the effect of H. pylori on IL-10 expression. Furthermore, upregulated IL-10 expression was significantly suppressed in H. pylori-pulsed MDDCs by histone acetyltransferase and methyltransferase inhibitors. Taken together, impaired DC function contributes to the less effective innate and adaptive immune responses against H. pylori seen in gastric cancer patients. H. pylori can regulate IL-10 production through Toll-like and DC-SIGN receptors, activates p-p38 MAPK signaling and the transcription factors NF-kB, and modulates histone modification.

Endovascular therapy for distal hilar renal artery aneurysm: a case report and literature review.

Renal artery aneurysm (RAA), a type of visceral aneurysm with atypical symptoms, is difficult to detect and is usually discovered incidentally by imaging examination. Hilar RAA (HRAA) represents a relatively rare subgroup of RAA that is located in the distal part of the renal artery, close to the renal parenchyma. We reported a 55-year-old woman with an HRAA measuring 19 mm × 20 mm × 20 mm. She underwent endovascular therapy with bare-metal stent implantation with nested coil embolization. She was discharged without complications. The uniqueness of this case is the aneurysm location, which was at the distal right renal artery, making it difficult to preserve the blood supply to the right kidney. The novelty of the minimally invasive technique was that this endovascular treatment not only eliminated the aneurysm, but also preserved the blood supply to the ipsilateral kidney. Endovascular therapy is effective in the management of HRAA.

Detection of a novel Pestivirus strain in Java ticks (Amblyomma javanense) and the hosts Malayan pangolin (Manis javanica) and Chinese pangolin (Manis pentadactyla).

Pangolins are endangered animals and are listed in the CITES Appendix I of the Convention International Trade Endangered Species of Wild Fauna and Flora as well as being the national first-level protected wild animal in China. Based on a few reports on pangolins infected with pestiviruses of the Flaviviridae family, Pestivirus infections in pangolins have attracted increasing attention. Pangolin pestivirus is a pathogen that may cause diseases such as acute diarrhea and acute hemorrhagic syndrome. To better understand the epidemiology and genomic characterization of pestiviruses carried by pangolins, we detected pestiviruses in dead Malayan pangolin using metavirome sequencing technology and obtained a Pestivirus sequence of 12,333 nucleotides (named Guangdong pangolin Pestivirus, GDPV). Phylogenetic tree analysis based on the entire coding sequence, NS3 gene or RdRp gene sequences, showed that GDPV was closely related to previously reported pangolin-derived Pestivirus and clustered into a separate branch. Molecular epidemiological investigation revealed that 15 Pestivirus-positive tissues from two pangolins individuals with a positivity rate of 5.56%, and six Amblyomma javanense carried pestiviruses with a positivity rate of 19.35%. Moreover, the RdRp gene of the Pestivirus carried by A. javanense showed a high similarity to that carried by pangolins (93-100%), indicating A. javanense is likely to represent the vector of Pestivirus transmission. This study expands the diversity of viruses carried by pangolins and provides an important reference value for interrupting the transmission route of the virus and protecting the health of pangolins.

Current Status and Prospect of Stent Placement for May-Thurner Syndrome.

Stent implantation has been proven to be safe and has become the first-line intervention for May-Thurner syndrome (MTS), with satisfactory mid-term patency rates and clinical outcomes. Recent research has demonstrated that catheter-directed thrombolysis is the preferred strategy when MTS is combined with deep vein thrombosis after self-expanding stent placement. However, the stent used for the venous system was developed based on the experience obtained in the treatment of arterial disease. Consequently, relatively common corresponding complications may come along later, which include stent displacement, deformation, and obstruction. Different measures such as adopting a stent with a larger diameter, improving stent flexibility, and increasing stent strength have been employed in order to prevent these complications. The ideal venous stent is presently being evaluated and will be introduced in detail in this review.

The complete chloroplast genome sequence of Camellia rostrata S. X. Yang & S. F. Chai (Theaceae), a critically endangered yellow camellia from southwest China.

Camellia rostrata S. X. Yang & S. F. Chai is a recently described yellow camellia species from Guangxi, China. It is a critically endangered species according to the IUCN Red List Categories and Criteria. Here, we report the complete chloroplast (cp) genome based on next-generation sequencing technology. The complete cp genome of C. rostrata is 156,547 bp in length and consists of a large single-copy (LSC, 86,199 bp) region, a small single-copy (SSC, 18,204 bp) region, and a pair of inverted repeats (IRs, 26,072 bp). The genome contains 135 genes including 40 tRNA, eight rRNA, and 87 protein-coding genes. Phylogenetic analysis resolved C. rostrata in a clade containing C. huana and C. impressinervis, both of which are classified to Camellia sect. Archecamellia. Our findings support the placement of C. rostrata in C. sect. Archecamellia as proposed by a previous study. The cp genome of C. rostrata provides valuable bioinformatic resources for the protection and utilization of this yellow camellia species.

The complete chloroplast genome sequence of Camellia zhaiana (Theaceae), a critically endangered species from China.

Camellia zhaiana S.X. Yang (Theaceae) is a recently described species reported from Guangxi, China. It was proposed as a critically endangered species according to the IUCN Red List Categories and Criteria. In this study, we report and characterize the complete chloroplast (cp) genome of C. zhaiana using Illumina pair-end sequencing data. This is the first report of a cp genome of a species classified in Camellia section. Longipedicellata. The cp genome of C. zhaiana is 156,627 bp in length and includes a large single-copy region (LSC, 86,196 bp), a small single-copy region (SSC, 18,281 bp), and a pair of inverted repeat regions (IRs, 26,075 bp). The genome contains 135 genes, including 40 tRNA, eight rRNA, and 87 protein-coding genes. Phylogenetic analysis showed a strongly supported sister relationship between C. zhaiana and C. longipedicellata, which is a species classified in sect. Longipedicellata. These data support the previous systematic findings of C. zhaiana and advance the bioinformatics of the genus Camellia.

Novel flexible Fenton-like catalyst: Unique CuO nanowires arrays on copper mesh with high efficiency across a wide pH range.

Free-standing and flexible Cu@CuO nanowires (NWs) mesh as an easily recycled Fenton-like catalyst is developed for the first time. Dense CuO nanowire arrays were uniformly grown on a copper mesh surface simply by wet etching accompanied with thermal dehydration. These dense CuO NWs provide a large specific area and therefore guarantee excellent catalytic performance toward the degradation of rhodamine B (RhB). With a k-value of 0.23 min-1, such a Cu@CuO NWs mesh is able to degrade 100% RhB in only 16 min. This Fenton-like catalyst is also appropriate for degrading other organic dyes, including crystal violet, methylene blue, and rhodamine 6G. Unlike the conventional Fenton catalyst implemented at a pH value around 3, the Cu@CuO NWs mesh could adapt to a wide pH range from 2.1 to 12.0. More intriguingly, the Cu@CuO NWs mesh with excellent flexibility could be easily recycled after catalysis, which is a significant advance compared to the previously reported Fenton catalysts in the form of powders or nanoparticles. In addition, the recycling performance of this Cu@CuO NWs mesh was also assessed. On the basis of electron spin resonance (ESR) results, O2- rather than OH is the main active species for the dye degradation by the Cu@CuO NWs mesh. With a marvelous combination of excellent flexibility, wide pH adaptation, and high efficiency, this easily recycled three dimensional Cu@CuO NWs architecture can afford new ideas for the Fenton chemistry.