An unconventional SNARE complex mediates exocytosis at the plasma membrane and vesicular fusion at the apical annuli in Toxoplasma gondii.

Exocytosis is a key active process in cells by which proteins are released in bulk via the fusion of exocytic vesicles with the plasma membrane. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein-mediated vesicle fusion with the plasma membrane is essential in most exocytotic pathways. In mammalian cells, the vesicular fusion step of exocytosis is normally mediated by Syntaxin-1 (Stx1) and SNAP25 family proteins (SNAP25 and SNAP23). However, in Toxoplasma gondii, a model organism of Apicomplexa, the only SNAP25 family protein, with a SNAP29-like molecular structure, is involved in vesicular fusion at the apicoplast. Here, we reveal that an unconventional SNARE complex comprising TgStx1, TgStx20, and TgStx21 mediates vesicular fusion at the plasma membrane. This complex is essential for the exocytosis of surface proteins and vesicular fusion at the apical annuli in T. gondii.

LncRNA HOTAIR Inhibits miR-19a-3p to Alleviate Foam Cell Formation and Inflammatory Response in Atherosclerosis.

Background: Atherosclerosis, a chronic inflammatory disease, poses a significant risk for cardiovascular disorders. Meanwhile, emerging evidence suggests that long noncoding RNAs (lncRNAs) play pivotal roles in diverse cardiovascular conditions. Nonetheless, the functional implications of lncRNAs in atherosclerosis remain largely unexplored. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess lncRNA HOTAIR and miR-19a-3p expression levels in patients with atherosclerosis and macrophage-derived foam cells. The release of inflammatory factors was evaluated using enzyme-linked immunosorbent assay (ELISA), while lipid uptake by foam cells was assessed through Oil Red O staining. Additionally, the targeting relationship between lncRNA HOTAIR and miR-19a-3p was validated via a Luciferase reporter assay. Results: LncRNA HOTAIR exhibited downregulation in the plasma of atherosclerosis patients and was found to be inhibited by ox-LDL in human macrophage-derived foam cells. Overexpression of HOTAIR effectively reduced lipid uptake and suppressed the inflammatory response by downregulating the expression of TNF-α and IL-6 during foam cell formation. Mechanistically, HOTAIR mitigated foam cell formation by repressing the expression of miR-19a-3p. Conclusions: In conclusion, our findings, in conjunction with previous studies, elucidate the role of HOTAIR in atherosclerosis. Specifically, we demonstrate that HOTAIR plays a role in alleviating foam cell formation and suppressing the inflammatory response by inhibiting miR-19a-3p in the context of atherosclerosis. Our results suggest the involvement of the TNF-α/miR-19a/HBP1/MIF pathway in mediating these effects. These findings contribute to a better understanding of atherosclerosis's molecular mechanisms and highlight the potential therapeutic implications of targeting HOTAIR and its associated pathways.

Transcriptome Analysis Reveals Endogenous Hormone Changes during Spike Development in Phalaenopsis.

Phalaenopsis orchids are popular worldwide due to their high ornamental and economic value; the spike and inflorescence formation of their flowers could be efficiently controlled under proper conditions. In this study, transcriptomic profiles and endogenous hormone changes were investigated to better understand the spike formation of Phalaenopsis. Morphological observations revealed four spike initiation statuses (i.e., S0: the status refers to axillary buds remaining dormant in the leaf axils; S1: the status refers to the 0.5 cm-long initial spike; S2: the status refers to the 1 cm-long spike; S3: the status refers to the 3 cm-long spike) during the process of spike development, while anatomical observations revealed four related statuses of inflorescence primordium differentiation. A total of 4080 differentially expressed genes were identified based on pairwise comparisons of the transcriptomic data obtained from the S0 to S3 samples; high levels of differential gene expression were mostly observed in S1 vs. S2, followed by S0 vs. S1. Then, the contents of 12 endogenous hormones (e.g., irindole-3-acetic acid (IAA), salicylic acid (SA), abscisic acid (ABA), gibberellins, and cytokinins) were measured. The results showed that the ABA content was decreased from S0 to S1, while the gibberellic acid 1 (GA1) content exhibited an opposite trend, indicating the reduction in ABA levels combined with the increase in GA1 levels in S0 promoted the axillary bud dormancy breaking, preparing for the following spike initiation. The GA20 oxidase and ABA 8'-hydroxylase genes, which are involved in endogenous hormone metabolism and signaling pathways, displayed similar expression patterns, suggesting they were probably the key genes participating in the GA and ABA regulation. Taken together, the findings of this study indicate that GA and ABA may be the key endogenous hormones breaking the dormancy and promoting the germination of axillary buds in Phalaenopsis.

The Sec1/Munc18-like proteins TgSec1 and TgVps45 play pivotal roles in assembly of the pellicle and sub-pellicle network in Toxoplasma gondii.

Post-Golgi vesicle trafficking is indispensable for precise movement of proteins to the pellicle, the sub-pellicle network and apical secretory organelles in Apicomplexa. However, only a small number of molecular complexes involved in trafficking, tethering and fusion of vesicles have been identified in Toxoplasma gondii. Consequently, it is unclear how complicated vesicle trafficking is accomplished in this parasite. Sec1/Munc18-like (SM) proteins are essential components of protein complexes involved in vesicle fusion. Here, we found that depletion of the SM protein TgSec1 using an auxin-inducible degron-based conditional knockout strategy led to mislocalization of plasma membrane proteins. By contrast, conditional depletion of the SM protein TgVps45 led to morphological changes, asymmetrical loss of the inner membrane complex and defects in nucleation of sub-pellicular microtubules, polarization and symmetrical assembly of daughter parasites during repeated endodyogeny. TgVps45 interacts with the SNARE protein TgStx16 and TgVAMP4-1. Conditional ablation of TgStx16 causes the similar growth defect like TgVps45 deficiency suggested they work together for the vesicle fusion at TGN. These findings indicate that these two SM proteins are crucial for assembly of pellicle and sub-pellicle network in T. gondii respectively.

The Feasibility and Effectiveness of Wearable Sensor Technology in the Management of Elderly Diabetics with Foot Ulcer Remission: A Proof-Of-Concept Pilot Study with Six Cases.

AIMS: Using specials wearable sensors, we explored changes in gait and balance parameters, over time, in elderly patients at high risk of diabetic foot, wearing different types of footwear. This assessed the relationship between gait and balance changes in elderly diabetic patients and the development of foot ulcers, in a bid to uncover potential benefits of wearable devices in the prognosis and management of the aforementioned complication. METHODS: A wearable sensor-based monitoring system was used in middle-elderly patients with diabetes who recently recovered from neuropathic plantar foot ulcers. A total of 6 patients (age range: 55-80 years) were divided into 2 groups: the therapeutic footwear group (n = 3) and the regular footwear (n = 3) group. All subjects were assessed for gait and balance throughout the study period. Walking ability and gait pattern were assessed by allowing participants to walk normally for 1 min at habitual speed. The balance assessment program incorporated the "feet together" standing test and the instrumented modified Clinical Test of Sensory Integration and Balance. Biomechanical information was monitored at least 3 times. RESULTS: We found significant differences in stride length (p < 0.0001), stride velocity (p < 0.0001), and double support (p < 0.0001) between the offloading footwear group (OG) and the regular footwear group on a group × time interaction. The balance test embracing eyes-open condition revealed a significant difference in Hip Sway (p = 0.004), COM Range ML (p = 0.008), and COM Position (p = 0.004) between the 2 groups. Longitudinally, the offloading group exhibited slight improvement in the performance of gait parameters over time. The stride length (odds ratio 3.54, 95% CI 1.34-9.34, p = 0.018) and velocity (odds ratio 3.13, 95% CI 1.19-8.19, p = 0.033) of OG patients increased, converse to the double-support period (odds ratio 6.20, 95% CI 1.97-19.55, p = 0.002), which decreased. CONCLUSIONS: Special wearable devices can accurately monitor gait and balance parameters in patients in real time. The finding reveals the feasibility and effectiveness of advanced wearable sensors in the prevention and management of diabetic foot ulcer and provides a solid background for future research. In addition, the development of foot ulcers in elderly diabetic patients may be associated with changes in gait parameters and the nature of footwear. Even so, larger follow-up studies are needed to validate our findings.

NH4I-Triggered [4 + 2] Annulation of α,ß-Unsaturated Ketoxime Acetates with N-Acetyl Enamides for the Synthesis of Pyridines.

The NH4I-triggered formal [4 + 2] annulation of α,ß-unsaturated ketoxime acetates with N-acetyl enamides has been developed. The current protocol employs electron-rich enamides as C2 synthons and enables the efficient and straightforward construction of polysubstituted pyridines in moderate to good yields based on metal-free systems. The reaction tolerates a wide range of functional groups and represents an alternate route toward the synthesis of pyridine derivatives.

Diminished 25-OH vitamin D3 levels and vitamin D receptor variants are associated with susceptibility to type 2 diabetes with coronary artery diseases.

BACKGROUND: Role of plasma vitamin D and genetic variants of its receptor (VDR) in susceptibility to different diseases has been documented. Various studies in different populations have been highlighted strong associations with diabetes and cardiovascular diseases. Vitamin D deficiency has been linked with the development of type 2 diabetes (T2D) and the onset of coronary artery diseases (CAD). However, the role of vitamin D in predisposition to CAD in patients with T2D is ill-defined. MATERIALS AND METHODS: We enrolled 674 Chinese T2D patients, and based on clinical phenotype, patients were further categorized into patients with (n = 138) or without coronary artery disease (n = 536). Five hundred twenty-one healthy subjects from similar geographical areas, free from diabetic or coronary disorders, were enrolled as controls. Serum levels of 25-OH vitamin D were quantified by ELISA. Common VDR (FokI, TaqI, BsmI, and ApaI) polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Patients with T2D displayed lower levels of 25-OH vitamin D compared with healthy controls. Furthermore, T2D patients with CAD clinical phenotype had the lowest levels of vitamin D. Prevalence of FokI and TaqI mutants was significantly higher in diabetic patients when compared to controls. Interestingly, Tt genotype was more frequent in the artery disease group in comparison with T2D patients without heart involvement. Combined analysis of VDR polymorphisms and serum levels of vitamin D revealed a significant role in predisposition to T2D with or without CAD. CONCLUSIONS: Lower vitamin D levels and variants of VDR polymorphisms (FokI and TaqI) are associated with susceptibility to T2D and clinical manifestation.

Bardoxolone treatment alleviates lipopolysaccharide (LPS)-induced acute lung injury through suppressing inflammation and oxidative stress regulated by Nrf2 signaling.

Nuclear factor-erythroid 2 related factor 2 (Nrf2) plays critical roles in attenuating various inflammation- and oxidative stress-induced diseases, including acute lung injury (ALI). Bardoxolone (Bard), a synthetic triterpenoid based on natural product oleanolic acid, is one of the most potent Nrf2 activator. However, if Bard could prevent lipopolysaccharide (LPS)-induced ALI by inducing Nrf2 activation and its down-streaming signals, is still poorly understood. In this study, we attempted to explore the protective effect of Bard on ALI and the underlying molecular mechanisms. The results indicated that Bard significantly attenuated ALI through reducing the lung wet/dry weight ratio and protein concentration, neutrophil infiltration, malondialdehyde (MDA) and myeloperoxidase (MPO) levels, and improving superoxide dismutase (SOD) and glutathione (GSH) activities. In addition, Bard effectively ameliorated histopathological alterations, reactive oxygen species (ROS) production, pro-inflammatory cytokines release, and the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX2) and high mobility group box 1 (HMGB1). Moreover, the inhibitory role of Bard in inflammation was also attributed to its suppression of nuclear factor-κB (NF-κB) signaling. Furthermore, the activation of mitogen-activated protein kinases (MAPKs) signaling, including p38, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK), induced by LPS was substantially ameliorated by Bard. The beneficial effects of Bard on ALI were confirmed in LPS-incubated cells in vitro. Meanwhile, the in vitro studies also demonstrated that Bard-improved ALI was largely due to its role in inducing Nrf2 signaling through a dose-dependent manner. Importantly, we found that Bard-attenuated histological changes, inflammation, ROS production, NF-κB and MAPKs signaling in Nrf2+/+ mice were significantly abolished in mice with Nrf2 knockout. Therefore, our study for the first time provided evidence that Bard could effectively ameliorate LPS-induced ALI by reducing oxidative stress and inflammation mainly through the activation of Nrf2 signaling.

Coupling of a whispering gallery mode to a silicon chip with photonic crystal.

We demonstrate the efficient coupling (99.5%) of a silica whispering gallery mode microresonator directly with a silicon chip by using a silicon photonic crystal waveguide as a coupler. The efficient coupling is attributed to the small effective refractive index difference between the two devices. The large group index of the photonic crystal waveguide mode also contributes to the efficient coupling. A coupling Q of 2.68×106 is obtained, which allows us to achieve the critical coupling of a silica whispering gallery mode with an intrinsic Q of close to 107 with a Si chip.

Cascaded chirped narrow bandpass filter with flat-top based on two-dimensional photonic crystals.

We propose a structure of a cascaded chirped narrow bandpass filter with a flat-top based on two-dimensional (2D) photonic crystals (PhCs). The filter discussed here consists of three filter units, each with a resonator and two reflectors. Coupled mode theory and transfer matrix method are methodologies applied in the analysis of the features. The calculations show that the bandwidth of the filter can be adjusted by changing the distances between resonators and reflectors, and based on this, a flat-top response can be achieved by chirped-cascading the filter units. According to the theoretical model, we design a narrow bandpass filter based on 2D PhCs with a triangular lattice of air holes, the parameters of which are calculated using the finite element method. The simulation results show that the filter has a center frequency of 193.40 THz, an insertion loss of 0.18 dB, a flat bandwidth of 40 GHz, and ripples of about 0.2 dB in the passband. The filter is suitable for dense-wavelength-division-multiplexed optical communication systems with 100 GHz channel spacing.

Multi/demulti-plexer based on transverse mode conversion in photonic crystal waveguides.

A novel mode multiplexer and demultiplexer (MMUX/DEMMUX) based on 2-D photonic crystal (PC) at 1550 nm is proposed. The PC-based mode MMUX/DEMMUX including mode conversion function with a single-mode and multi-mode waveguides can be realized by quasi phase-matching TE(0) & TE(1) modes of two waveguides. 2DFinite-Difference-Time-Domain and beam propagation methods are used for simulation. The results show that PC-based mode MMUX/DEMMUX has the potential for high-capacity MDM optical communication systems with a low insertion loss (<0.36dB), low mode crosstalk (< -20.9 dB) and wide bandwidth (~100 nm).

Apelin attenuates the osteoblastic differentiation of aortic valve interstitial cells via the ERK and PI3-K/Akt pathways.

Aortic valve calcification (AVC), which used to be recognized as a passive and irreversible process, is now widely accepted as an active and regulated process characterized by osteoblastic differentiation of aortic valve interstitial cells (AVICs). Apelin, the endogenous ligand for G-protein-coupled receptor APJ, was found to have protective cardiovascular effects in several studies. However, the effects and mechanisms of apelin on osteoblastic differentiation of AVICs have not been elucidated. Using a pro-calcific medium, we devised a method to produce calcific human AVICs. These cells were used to study the relationship between apelin and the osteoblastic calcification of AVICs and the involved signaling pathways. Alkaline phosphatase (ALP) activity/expression and runt-related transcription factor 2 (Runx2) expression were examined as hallmark proteins in this research. The involved signaling pathways were studied using the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and the phosphatidylinositol 3-kinase (PI3-K) inhibitor, LY294002. The results indicate that apelin attenuates the expression and activity of ALP, the expression of Runx2, and the formation of mineralized nodules. This protective effect was dependent on the dose of apelin, reaching the maximum at 100 pM, and was connected to activity of ERK and Akt (a downstream effector of PI3-K). The activation of ERK and PI3-K initiated the effects of apelin on ALP activity/expression and Runx2, but PD98059 and LY294002 abolished the effect. These results demonstrate that apelin attenuates the osteoblastic differentiation of AVICs via the ERK and PI3-K/Akt pathway.

Clinical significance and detection of microRNA-21 in serum of patients with diffuse large B-cell lymphoma in Chinese population.

BACKGROUND: Expression patterns of microRNAs in serum are involved in potentially non-invasive biomarkers for various diseases. The purpose of this study is to examine the expression of miR-21 in serum of patients with diffuse large B-cell lymphoma (DLBCL) and to validate the significance of miR-21 in early diagnosis, genotyping, treatment options as well as its prognosis estimates of Chinese DLBCL. METHODS: miR-21 expression was detected by fluorescent quantity polymerase chain reaction (qPCR) in 9 DLBCL cell lines (OCI-Ly1, OCI-Ly3, OCI-Ly4, OCI-Ly7, OCI-Ly8, OCI-Ly10, OCI-Ly18, OCI-Ly19, and HBL), as well as in tumor tissue and serum samples from patients with DLBCL (germinal center B-cell-like (GCB) DLBCL 32; activated B-cell-like (ABC) DLBCL 30) and 50 healthy subjects. RESULTS: Expression of miR-21 was increased in DLBCL cell lines. Compared with the miR-21 expression of GCB subgroup (OCI-Ly1, OCI-Ly4, OCI-Ly7, OCI-Ly8, OCI-Ly18, OCI-Ly19), ABC subgroup (OCI-Ly3, OCI-Ly10, and HBL) has higher expression (t = 11.18, P < 0.01). Circulating miR-21 level in sera from patients with DLBCLwas associated with matched tumor tissue (r(2) = 0.931, P < 0.0001). Consistent with the in vitro, miR-21 expression levels in serum of patients with DLBCL [21.38(10.26-45.21)] were higher than those in serum of control cases [1.87(1.05-3.97); U = 168, P = 0.000]. Moreover, miR-21 expression levels in serum of patients with subgroup ABC [28.68(14.92~98.44)] were higher than that of patients with subgroup GCB [18.3(7.32~33.46); U = 336, P = 0.043]. miR-21 expression in serum of DLBCL with stage I and II were higher than those in stage III and IV (U = 62, P = 0.013 in GCB type; U = 53, P = 0.014 in ABC type). Compared with relapse-free survival in patients with DLBCL, high expression of miR-21 was associated with well prognosis (U = 259, P = 0.035). CONCLUSION: miR-21 expressed in the serum of patients with DLBCL from Chinese was associated with clinical stage, molecular subgroup, and prognosis estimates. miR-21 may be served as a biomarker in early diagnosis, genotyping, treatment options, and prognosis estimating of Chinese DLBCL.

Preparation of metal-organic framework combined with Portulaca oleracea L. extract electrostatically spun nanofiber membranes delayed release wound dressing.

In this study, we prepared a polyacrylonitrile (PAN) composite nanofiber membrane comprising Portulaca oleracea L. extract (POE) and a zinc-based metal-organic framework (MOF) by an in situ growth method as a potentially new type of wound dressing with a slow drug-release effect, to solve the problem of the burst release of drugs in wound dressings. The effects of the MOF and POE doping on the nanofiber membranes were examined using scanning electron microscopy (SEM) and FTIR spectroscopy. SEM analysis revealed the dense and uniform attachment of MOF particles to the surface of the nanofiber membrane, while FTIR spectroscopy confirmed the successful fusion of MOF and POE. Furthermore, investigations into the water contact angle and swelling property demonstrated that the incorporation of the MOF and POE enhanced the hydrophilicity of the material. The results of the in vitro release test showed that the cumulative release rate for PAN/MOF/POE60 decreased from 66.5 ± 2.34% to 32.18 ± 1.31% in the initial 4 h and from 90.54 ± 0.79% to 65.92 ± 1.95% in 72 h compared to PAN/POE, indicating a slowing down of the drug release. In addition, the antimicrobial properties of the fiber membranes were evaluated by the disc diffusion method, and it was evident that the PAN/MOF/POE nanofibers exhibited strong inhibition against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The antioxidant properties of the nanofiber membranes loaded with POE were further validated through the DPPH radical scavenging test. These findings highlight the potential application of the developed nanofiber membranes in wound dressings, offering controlled and sustained drug-release capabilities.

[Silver nanoparticles-resistance of HeLa cell associated with its unusually high concentration of α-ketoglutarate and glutathione].

Silver nanoparticles (AgNPs) is known as one of the most valuable metal nanoparticles in antibacterial and anticancer application. AgNPs-resistant bacteria has been documented, but it is unclear whether cancer cells can also escape the anti-cancer effect of AgNPs. In this study, we aimed to investigate this phenomenon and its underlying mechanism. The antibacterial activity and cytotoxicity of AgNPs were measured in the presence of HeLa cell metabolites. The status of AgNPs in the system associated with metabolites were characterized by UV-Vis, Zetasizer Nano ZS, and transmission electron microscopy. Non-targeted metabolomics was used to reveal the metabolites components that bind with AgNPs. HeLa cells were injected intraperitoneally to establish the tumor-bearing mice model, and the stability of AgNPs in mice serum was analyzed. The results manifested that HeLa cell metabolites inhibited the anticancer and antibacterial effects of AgNPs in a dose-dependent manner by causing AgNPs aggregation. Effective metabolites that inhibited the biological activity of AgNPs were stable in 100 ℃, insoluble in chloroform, containing sulfur elements, and had a molecular weight less than 1 kDa in molecular weight. There were 115 compounds bound with AgNPs. In vitro experiments showed that AgNPs aggregation occurred only when the concentration of α-ketoglutarate (AKG) and glutathione (GSH) together reached a certain threshold. Interestingly, the concentration of AKG and GSH in HeLa cellular metabolites was 10 and 6 times higher than that in normal cervical epithelial cells, respectively, which explained why the threshold was reached. Furthermore, the stability of AgNPs in the serum of tumor-bearing mice decreased by 20% (P < 0.05) compared with the healthy mice. In conclusion, our study demonstrates that HeLa cells escaped the anti-cancer effect of AgNPs through the synergistic effect of AKG and GSH, suggesting the need to develop strategies to overcome this limitation.

Apicoplast biogenesis mediated by ATG8 requires the ATG12-ATG5-ATG16L and SNAP29 complexes in Toxoplasma gondii.

In apicomplexan parasites, the macroautophagy/autophagy machinery is repurposed to maintain the plastid-like organelle apicoplast. Previously, we showed that in Toxoplasma and Plasmodium, ATG12 interacts with ATG5 in a non-covalent manner, in contrast to the covalent interaction in most organisms. However, it remained unknown whether apicomplexan parasites have functional orthologs of ATG16L1, a protein that is essential for the function of the covalent ATG12-ATG5 complex in vivo in other organisms. Furthermore, the mechanism used by the autophagy machinery to maintain the apicoplast is unclear. We report that the ATG12-ATG5-ATG16L complex exists in Toxoplasma gondii (Tg). This complex is localized on isolated structures at the periphery of the apicoplast dependent on TgATG16L. Inducible depletion of TgATG12, TgATG5, or TgATG16L caused loss of the apicoplast and affected parasite growth. We found that a putative soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) protein, synaptosomal-associated protein 29 (TgSNAP29, Qbc SNARE), is required to maintain the apicoplast in T. gondii. TgSNAP29 depletion disrupted TgATG8 localization at the apicoplast. Additionally, we identified a putative ubiquitin-interacting motif-docking site (UDS) of TgATG8. Mutation of the UDS site abolished TgATG8 localization on the apicoplast but not lipidation. These findings suggest that the TgATG12-TgATG5-TgATG16L complex is required for biogenesis of the apicoplast, in which TgATG8 is translocated to the apicoplast via vesicles in a SNARE -dependent manner in T. gondii.Abbreviations: AID: auxin-inducible degron; CCD: coiled-coil domain; HFF: human foreskin fibroblast; IAA: indole-3-acetic acid; LAP: LC3-associated phagocytosis; NAA: 1-naphthaleneacetic acid; PtdIns3P: phosphatidylinositol-3-phosphate; SNARE: soluble N-ethylmaleimide sensitive factor attachment protein receptor; UDS: ubiquitin-interacting motif-docking site; UIM: ubiquitin-interacting motif.

Protective effects of Salvianic acid A against multiple-organ ischemia-reperfusion injury: a review.

Ischemia-reperfusion (I/R) injury refers to a new injury caused by reperfusion after the restoration of ischemic tissue or organ blood supply. Salvianic acid A (danshensu) is a primary active ingredient extracted from Salvia miltiorrhiza. It has a protective function against I/R injury in the cardiovascular system, brain, liver, kidney, gastrointestinal tract, and other organs. This article reviews evidence of the protective effects of Salvianic acid A and its potential mechanisms of action in organ I/R injury protection. The aim of this review is to investigate the role of Salvianic acid A in the treatment of I/R injury, providing a reference resource that could facilitate subsequent studies.

Serum protein coating enhances the antisepsis efficacy of silver nanoparticles against multidrug-resistant Escherichia coli infections in mice.

Antimicrobial resistance poses a significant threat to public health and social development worldwide. This study aimed to investigate the effectiveness of silver nanoparticles (AgNPs) in treating multidrug-resistant bacterial infections. Eco-friendly spherical AgNPs were synthesized using rutin at room temperature. The biocompatibility of both polyvinyl pyrrolidone (PVP) and mouse serum (MS)-stabilized AgNPs was evaluated at 20 µg/mL and showed a similar distribution in mice. However, only MS-AgNPs significantly protected mice from sepsis caused by the multidrug-resistant Escherichia coli (E. coli) CQ10 strain (p = 0.039). The data revealed that MS-AgNPs facilitated the elimination of Escherichia coli (E. coli) in the blood and the spleen, and the mice experienced only a mild inflammatory response, as interleukin-6, tumor necrosis factor-α, chemokine KC, and C-reactive protein levels were significantly lower than those in the control group. The results suggest that the plasma protein corona strengthens the antibacterial effect of AgNPs in vivo and may be a potential strategy for combating antimicrobial resistance.

[Primary culture and identification of glomerular mesangial cells from mice with spontaneous lupus nephritis].

Objective To perform primary culture of glomerular mesangial cells, identify them from a mouse model of spontaneous lupus nephritis model and explore the optimal conditions for these procedures. Methods Nine control ICR mice and nine model MRL/lpr mice with spontaneous lupus nephritis were tested for autoantibodies using ELISA and urine protein was detected by bicinchoninic acid (BCA) assay at 12, 14 and 18 weeks of age. HE and Masson staining were used to observe the pathological changes of mice with lupus nephritis. Glomeruli were isolated using a cell sieve, while primary culture of glomerular mesangial cells was performed using the eugenic selection method. Glomerular mesangial cells of the MRL/lpr mice were identified based on cell morphology and immunocytochemical staining of α-smooth muscle actin and nephrin. Results In the model group, levels of anti-nuclear antibody and anti-double-stranded DNA antibodies significantly increased. Urine protein levels also increased significantly at 14 and 18 weeks of age. HE and masson staining of kidney tissue revealed pathological changes associated with lupus nephritis in the MRL/lpr mice from 12 weeks of age. Twenty-five days after seeding of the glomerular mesangial cells, those from the MRL/lpr mice gradually covered the bottom of the culture flasks, appearing star-shaped and fusiform by phase contrast microscopy. Immunocytochemistry showed that these cells were α-smooth muscle actin-positive and nephrin-negative, thus ruling out other glomerular intrinsic cells. Conclusion The primary culture of glomerular mesangial cells from mice with spontaneous lupus nephritis is developed and characterized.

Custom-Molded Offloading Footwear Effectively Prevents Recurrence and Amputation, and Lowers Mortality Rates in High-Risk Diabetic Foot Patients: A Multicenter, Prospective Observational Study.

BACKGROUND: Recurrence of high-risk diabetic feet, after wound, healing is a common challenge among diabetic patients. Continuous use of an offloading device significantly prevents recurrence of high-risk diabetic feet, although patient adherence is imperative to ensuring this therapy's clinical efficacy. In this study, we explored clinical outcomes of patients with a high-risk diabetic foot who had been prescribed with custom-molded offloading footwear under different adherence conditions. METHODS: A total of 48 patients (17 females and 31 males) with high-risk diabetic feet, who had been with prescribed offloading footwear in 13 medical centers across 4 cities, were enrolled in the current study. The patients were assigned into either continuous offloading therapy (COT, n = 31) or interrupted offloading therapy (IOT, n = 17) groups, according to their adherence to the therapy. All patients were followed up monthly, and differences in recurrence, amputation, and deaths between the groups were analyzed at 4 months after therapy. RESULTS: Forty-eight patients met our inclusion criteria and were therefore included in the final analysis. Among them, 31 were stratified into the COT group and adhered to offloading therapy throughout the study period, whereas 17 were grouped as IOT and exhibited interrupted adherence to offloading therapy. We found statistically significant differences in recurrence rates (0 vs 38.46%, p < 0.01), amputation (0 vs 11.76%, p < 0.01), and deaths (0% vs 5.88%, p < 0.01) between the groups during follow-up. CONCLUSION: Patients' adherence is imperative to efficacy of custom-molded offloading footwear during treatment of high-risk diabetic foot. Further studies are needed to elucidate the role of improved design of the offloading device and the need for enhanced patient education for improved adherence.