Amoxicillin-vonoprazan dual therapy for Helicobacter pylori eradication: A systematic review and meta-analysis.

BACKGROUND AND AIM: The efficacy and safety of amoxicillin-vonoprazan (VA) dual therapy remained unclear. METHODS: This systematic review was conducted in accordance with the PRISMA 2009 guidelines. A systematic search of the Pubmed, Embase, and Cochrane database was conducted using the combination of "Helicobacter pylori or H. pylori or Hp," "amoxicillin or penicillin," and "Vonoprazan or TAK-438 or Takecab or (potassium AND competitive) or potassium-competitive." The initial and secondary outcome of this meta-analysis was to evaluate the efficacy and safety of VA dual therapy. RESULTS: Three studies and 668 H. pylori infected patients were included in this meta-analysis. The crude eradication rate of VA dual therapy was 87.5% and 89.6% by ITT and PP analysis, respectively. No significant differences were observed regarding the VA dual therapy and vonoprazan-amoxicillin-clarithromycin (VAC) triple therapy according to ITT (RR = 0.99, 95% CI, 0.93-1.05, P = 0.65) and PP (RR = 0.99, 95% CI, 0.94-1.05, P = 0.82) analysis. The side effect of VA dual therapy was 19.1% (95% CI, 5.9-32.4), which was lower than that of VAC triple therapy but there was no statistical significance (RR = 0.75, 95% CI, 0.59-1.06, P = 0.12). CONCLUSION: VA dual therapy shows acceptable efficacy, good safety and avoid unnecessary antibiotic use in the first-line treatment for H. pylori infection. However, its application in other regions need to be further explored.

Cholinesterases and Engineered Mutants for the Detection of Organophosphorus Pesticide Residues.

Nowadays, pesticide residues constitute an increasing public health concern. Cholinesterases, acetylcholinesterase, and butyrylcholinesterase, are reported to be involved in detoxification processes owing to their capability of scavenging organophosphates and carbamates. Thus, these enzymes are targeted for the discovery of sensors aiming at detecting pesticide residues. In recent years, cholinesterase-based biosensors have attracted more and more attention in the detection of pesticides. Herein, this review describes the recent progress on the engineering of cholinesterases and the development of the corresponding sensors that could be used for the detection of organophosphorus pesticide residues.

Pyrazolone-quinazolone hybrids: a novel class of human 4-hydroxyphenylpyruvate dioxygenase inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (HPPD), converting 4-hydroxyphenylpyruvate acid to homogentisate, is an important target for treating type I tyrosinemia and alkaptonuria due to its significant role in tyrosine catabolism. However, only one commercial drug, NTBC, also known as nitisinone, has been available for clinical use so far. Herein, we have elucidated the structure-based design of a series of pyrazolone-quinazolone hybrids that are novel potent human HPPD inhibitors through the successful integration of various techniques including computational simulations, organic synthesis, and biochemical characterization. Most of the new compounds displayed potent inhibitory activity against the recombinant human HPPD in nanomolar range. Compounds 3h and 3u were identified as the most potent candidates with Ki values of around 10 nM against human HPPD, about three-fold more potent than NTBC. Molecular modeling indicated that the interaction between the pyrazolone ring and ferrous ion, and the hydrophobic interaction of quinazolone with its surrounding residues, such as Phe347 and Phe364, contributed greatly to the high potency of these inhibitors. Therefore, compounds 3h and 3u could be potentially useful for the treatment of type I tyrosinemia and other diseases with defects in tyrosine degradation.

[The profile of IGF2R gene expression and H3 histone modifications in replicative cell senescence].

OBJECTIVE: To study the profile of IGF2R expression and histone modifications in replicative cell senescence. METHODS: The changes of biological characteristics of young human pulmonary fibroblast (HPF) cells [at population doubling level (PDL) 23] and aging HPF cells (at PDL50) were observed and real-time quantitative PCR was utilized to investigate human IGF2R gene expressions profile during the process of cellular aging (at different PDL). Then chromatinimmunoprecipitation-real time quantitative PCR (CHIP-QPCR) methods were conducted to analyze histone modifications of the regions around the transcriptional start site of IGF2R (H3-Ac, H3K9-tri-Me, H3K9-Ac and H3K4-tri-Me). RESULTS: In contrast to young cells, the aging cells were bigger and less proliferative, their cell cycles arrest, and aging specific beta-galactosidase staining was positive. IGF2R gene expression was in positive correlation with PDL. H3-Ac, H3K9-Ac and H3K4-tri-Me were dominant in the upstream region (-0.6 kb) to the downstream region (+1.2 kb) of transcriptional start site (TSS). While in the downstream of TSS from +1.6 kb to +4.0 kb, H3K9-Ac was declined and H3K9-tri-Me was elevated in turn, but H3K4-tri-Me still prevailed in these areas. CONCLUSION: IGF2R is related to cell replicative senescence and its gene expression is regulated by histone modification of H3. Therefore, epigenetics may play a role in cell senescence.

Structure-based discovery of pyrazole-benzothiadiazole hybrid as human HPPD inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) has attracted increasing attention as a target for treating type I tyrosinemia and other diseases with defects in tyrosine catabolism. Only one commercial drug, 2-(2-nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC), clinically treat type I tyrosinemia, but show some severe side effects in clinical application. Here, we determined the structure of human HPPD-NTBC complex, and developed new pyrazole-benzothiadiazole 2,2-dioxide hybrids from the binding of NTBC. These compounds showed improved inhibition against human HPPD, among which compound a10 was the most active candidate. The Absorption Distribution Metabolism Excretion Toxicity (ADMET) predicted properties suggested that a10 had good druggability, and was with lower toxicity than NTBC. The structure comparison between inhibitor-bound and ligand-free form human HPPD showed a large conformational change of the C-terminal helix. Furthermore, the loop 1 and α7 helix were found adopting different conformations to assist the gating of the cavity, which explains the gating mechanism of human HPPD.

Rhythmic cilia changes support SCN neuron coherence in circadian clock.

The suprachiasmatic nucleus (SCN) drives circadian clock coherence through intercellular coupling, which is resistant to environmental perturbations. We report that primary cilia are required for intercellular coupling among SCN neurons to maintain the robustness of the internal clock in mice. Cilia in neuromedin S-producing (NMS) neurons exhibit pronounced circadian rhythmicity in abundance and length. Genetic ablation of ciliogenesis in NMS neurons enabled a rapid phase shift of the internal clock under jet-lag conditions. The circadian rhythms of individual neurons in cilia-deficient SCN slices lost their coherence after external perturbations. Rhythmic cilia changes drive oscillations of Sonic Hedgehog (Shh) signaling and clock gene expression. Inactivation of Shh signaling in NMS neurons phenocopied the effects of cilia ablation. Thus, cilia-Shh signaling in the SCN aids intercellular coupling.

[Etiology surveillance of hand-foot-mouth disease in Henan province between 2008 and 2011].

OBJECTIVE: To understand etiological types and distribution features of hand-foot-mouth disease (HFMD) in Henan province between 2008 and 2011. METHODS: A total of 30 486 specimens of feces, rectal swabs or throat swabs from HFMD patients were collected by each Municipal CDC in Henan from 2008 to 2011. The enterovirus 71 (EV71), coxsackie virus A16 (CA16) and other enterovirus (EV) were detected by RT-PCR or real time RT-PCR. The VP1 gene of EV71 was amplified and the sequences were analyzed by bioinformatics software. A genetic evolution tree of the sequence was constructed as well. RESULTS: The positive rates of EV71, CA16 and other EV were 62.70% (11 209/17 876), 12.03% (2150/17 876), 25.27% (4517/17 876) in 17 876 laboratory diagnosed cases, respectively. The differences were statistically significant (χ(2) = 157.17, P < 0.05). The positive rates of EV71, CA16 and other EV were 63.40% (7370/11 624), 11.58% (1346/11 624) and 25.02% (2908/11 624) in male patients and 61.40% (3839/6252), 12.86% (804/6252) and 25.74% (1609/6252) in female patients, respectively. The differences were statistically significant (χ(2) = 4.06, P < 0.05). The children under 5 years old were high-risk population of HFMD, accounting to 97.67% (17 459/17 876) of the laboratory-diagnosed patients.86.92% (15 537/17 876) cases were children between 1 to 3 years old. Constituent ratio of EV71 changed seasonally during a year, there was a high infection ratio of EV71 between April and June, especially in May, the infection ratio reached 69.34% (2384/3438). The positive rates of EV71, CA16 and other EV were 82.48% (5715/6929), 1.76% (122/6929) and 15.76% (1092/6929) among the 6929 laboratory-diagnosed severe cases, respectively. The positive rates of EV71 was higher than CA16 and other EV (χ(2) = 9259.17, 6170.81, P < 0.05, respectively). There were 117 deaths because of severe HFMD, 55 (47.01%) of which were laboratory confirmed. 50 death cases were infected by EV71, and according to the genetic evolution analysis, the VP1 gene of EV71 strain was belonged to subtype C4 of gene C. CONCLUSION: The EV71 and CA16 were the main pathogens which caused HFMD in Henan province, and EV71 virus was the dominant strain, belonging to C4 subtype of gene C.

Liproxstatin­1 induces cell cycle arrest, apoptosis, and caspase­3/GSDME­dependent secondary pyroptosis in K562 cells.

Leukemia is a fatal hematopoietic disorder with a poor prognosis. Drug resistance is inevitable after the long­term use of chemotherapeutic agents. Liproxstatin­1, commonly known as a ferroptosis inhibitor, has never been reported to have anticancer effects. In the present study, the antileukemic role of liproxstatin­1 in K562 leukemia cells was investigated. Liproxstatin­1 inhibited K562 cell proliferation in a dose­ and time­dependent manner. RNA sequencing revealed several pathways that were affected by liproxstatin­1, such as the G1/S transition of the mitotic cell cycle and extrinsic or intrinsic apoptotic signaling pathways. The results of flow cytometry indicated that liproxstatin­1 arrests the cell cycle at the G1 phase, and even at the G2/M phase. p21WAF1/CIP1, a cyclin­dependent kinase inhibitor, was upregulated. It was also determined that liproxstatin­1 induced BAX and TNF­α expression, which was accompanied by cleavage of caspase­3 and PARP. The caspase­3­specific inhibitor z­DEVD­FMK rescued some of the apoptotic cells. Interestingly, K562 cells were characterized by swelling and plasma membrane rupture when treated with a high concentration of liproxstatin­1, which was inconsistent with the typical apoptotic appearance. Thus, it was hypothesized that apoptosis­mediated pyroptosis occurs during liproxstatin­1­induced cell death. The expression of the hallmark of pyroptosis, the cleaved N­terminal GSDME, increased. Additionally, it was observed that endoplasmic reticulum stress and autophagy were involved in liproxstatin­1­induced cell death. Collectively, liproxstatin­1 induced cell cycle arrest, apoptosis, and caspase­3/GSDME­dependent secondary pyroptosis in K562 leukemia cells, which provides new hope for the treatment of leukemia.

Altered Spontaneous Brain Activity Patterns of Meibomian Gland Dysfunction in Severely Obese Population Measured Using the Fractional Amplitude of Low-Frequency Fluctuations.

Objective: Utilizing the fractional amplitude of low-frequency fluctuations (fALFF) technique, this study sought to correlate spontaneous cerebral abnormalities with the clinical manifestations of meibomian gland dysfunction (MGD) in severely obese (SO) population. Subjects and Methods: Twelve MGD patients in SO population (PATs) (4 males and 8 females) and twelve healthy controls (HCs) (6 males and 6 females) matched by gender and age were enrolled. Every participant underwent resting-state functional magnetic resonance imaging (rs-MRI) scanning. Spontaneous cerebral activity alterations were examined using the fALFF method. Receiver operating characteristic (ROC) curves were utilized to classify the medial fALFF values of the PATs and HCs. PATs were also asked to complete anxiety and depression score forms, permitting a correlation analysis. Results: In contrast with HCs, PATs had prominently increased fALFF values in the left lingual gyrus, the right globus pallidus, the right anterior cingulate and paracingulate gyri and the left middle occipital lobe (P < 0.05), and decreased fALFF values in the right cerebellum, the left fusiform gyrus, the right medial orbitofrontal gyrus, the left triangle inferior frontal gyrus and the left inferior parietal gyrus (P < 0.05). The results of the ROC curve indicated that changes in regional fALFF values might help diagnose MGD in SO population. Moreover, fALFF values in the right cerebellum of PATs were positively correlated with hospital anxiety and depression scores (HADS) (r = 0.723, P = 0.008). The fALFF values in the left triangle inferior frontal gyrus of PAT were negatively correlated with HADS (r = -0.651, P = 0.022). Conclusions: Aberrant spontaneous activity was observed in multiple regions of the cerebrum, offering helpful information about the pathology of MGD in SO population. Aberrant fALFF values in these regions likely relates to the latent pathologic mechanisms of anomalous cerebral activities in PATs.

Altered White Matter Integrity in Patients with Retinal Vein Occlusion: A Diffusion Tensor Imaging and Tract-Based Spatial Statistics Study.

BACKGROUND: To investigate microstructural alterations of white matter in retinal vein occlusion (RVO) patients by tract-based spatial statistics (TBSS) and diffusion tensor imaging (DTI). Material/Methods. DTI was performed on 14 RVO patients and 14 normal controls (HCs). We measured and recorded fractional anisotropy (FA) and radial diffusivity (RD) of white matter fibers and classified them through the receiver operating characteristic (ROC) curve and correlation analysis, respectively. RESULTS: The mean FA value of white matter in RVO patients is lower than the HCs, and the mean RD value in RVO patients increased, especially in the bilateral posterior thalamic, bilateral sagittal stratum, body of corpus callosum, cingulum, and fornix. The ROC curve of different brain regions showed high accuracy. Moreover, the mean FA and RD values were significantly correlated with visual and psychological disorders. CONCLUSION: TBSS could be regarded as an important method to reveal the alterations of white matter in RVO patients, indicating the underlying neurological mechanism of the RVO.

LUBAC regulates ciliogenesis by promoting CP110 removal from the mother centriole.

Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110-CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure. Here, we reveal that the linear ubiquitin chain assembly complex (LUBAC) plays an essential role in ciliogenesis by targeting the CP110-CEP97 complex. LUBAC specifically generates linear ubiquitin chains on CP110, which is required for CP110 removal from the mother centriole in ciliogenesis. We further identify that a pre-mRNA splicing factor, PRPF8, at the distal end of the mother centriole acts as the receptor of the linear ubiquitin chains to facilitate CP110 removal at the initial stage of ciliogenesis. Thus, our study reveals a direct mechanism of regulating CP110 removal in ciliogenesis and implicates the E3 ligase LUBAC as a potential therapy target of cilia-associated diseases, including ciliopathies and cancers.

[A study on visual development among preschool children].

OBJECTIVE: To evaluate the visual development and prevalence of amblyopia, strabismus among preschool children. METHODS: A random sample survey was performed in 4 610 preschool children from both urban and rural, aged 3 to 6 years. Participants underwent eye examination including visual acuity, refractive status, eye position, strabismus and amblyopia. RESULTS: Percentage of visual acuity above 1.0 was 28.4%, 39.3%, 46.2% and 76.5% in children of 3, 4, 5 and 6-year-old group, respectively. The mean visual acuity of each group was 0.63 ± 0.19 in 3-years old, 0.69 ± 0.16 in 4-year-old, 0.71 ± 0.22 in 5-year-old, 0.79 ± 0.29 in 6-year-old. Rural children have better vision acuity compared with those from urban. Hypermetropic was frequent refractive errors. Manifeststrabismus was found in 2.21%, with exotropia being more prevalence than esotropia; detection rate of recessive strabismus was 33.52%, mainly being exophoria; Based on current diagnostic criteria, the prevalence of amblyopia were 2.93% in 6 year-old group, 4.81% in 5-year-old group, 16.21% in 4-year-old group, 33.33% in 3-year-old group. CONCLUSION: Vision acuity is increasing with age in preschool population. A diagnosis standard of amblyopia suitable for each age group should be established to substitute the current one which has a high visual standard for amblyopia. Refractive error, strabismus and amblyopia are the leading causes of visual impairment among preschool-aged children, which represent the focus of prevention of blindness in preschool children.

Identification and verification of effective components of Huanghuai for dysfunctional uterine bleeding based on network pharmacology and molecular docking.

Objective: The Huanghuai (HH), which is made from the dried roots of Scutellaria baicalensis (Huangqin in Chinese) and the dried flowers and buds of Sophora japonica (Huaihua in Chinese), is a traditional Chinese formula used to treat dysfunctional uterine bleeding (DUB) (Benglou in Chinese) and proven to treat hemostasis effectively in our previous study. Network pharmacology and molecule docking were performed to study the underlying mechanism of Huanghuai (HH), and pharmacodynamic experiments were conducted to verify its curative effect. Methods: TCMSP, UniProt, GeneCards, STRING, DAVID databases, and Cytoscape 3.7.2 were utilized for the construction of a compound-target-pathway network. Docking the potential effective components with potential targets. The HPLC analysis of the potential effective components was performed. In vivo, the hot plate test model was used to study the analgesic activity, the egg white was used to study the swollen reaction in the sole in mice, and the hemostasis effect was studied by the capillary method, tail-breaking method and abortion uterus test. Results: The results showed that six compounds (acacetin, beta-sitosterol, wogonin, baicalein, kaempferol and quercetin) and four potential targets (PTGS2, AKT1, TP53 and TNF) in the compound-target-pathway network were the potential material basis for HH to treat DUB. It can be seen that the binding energy of the acacetin, wogonin, baicalein, beta-sitosterol, kaempferol and quercetin in HH docked with the receptor proteins PTGS2, AKT1, TP53, and TNF were far less than -5.0 kJ/mol, which means the molecules have low conformational energy, stable structure and high binding activity. And the result of HPLC analysis showed that acacetin, wogonin, baicalein, kaempferol and quercetin were the potential effective components of the hemostasis mechanism of HH, beta-sitosterol was removed due to low content. In vivo testing of the potential effective components, it revealed that the group of potential effective components identified by HPLC could increase the pain threshold, inhibit the swelling hind paws of mice induced by egg white, reduce the bleeding time and clotting time, reduce uterine bleeding, decrease the uterine weight, increase the content of Ca and ET-1, and reduce the content of NO in uterine homogenate tissue, and decrease of E2 and P content in uterine serum in aborted rats, whose efficacy was equal to HH. Conclusion: The results indicated that HH and potential active ingredient groups obtained from network pharmacology can treat DUB and play a hemostatic effect. The results obtained by network pharmacology have certain reliability. This study provides new indications for further mechanism research of HH on DUB and the development of HH or its components as an alternative therapy for patients with DUB. At the same time, the application of network pharmacology strategy may provide a powerful tool for exploring the mechanism of traditional Chinese medicine and discovering new biologically active ingredients.

CEP55 promotes cilia disassembly through stabilizing Aurora A kinase.

Primary cilia protrude from the cell surface and have diverse roles during development and disease, which depends on the precise timing and control of cilia assembly and disassembly. Inactivation of assembly often causes cilia defects and underlies ciliopathy, while diseases caused by dysfunction in disassembly remain largely unknown. Here, we demonstrate that CEP55 functions as a cilia disassembly regulator to participate in ciliopathy. Cep55-/- mice display clinical manifestations of Meckel-Gruber syndrome, including perinatal death, polycystic kidneys, and abnormalities in the CNS. Interestingly, Cep55-/- mice exhibit an abnormal elongation of cilia on these tissues. Mechanistically, CEP55 promotes cilia disassembly by interacting with and stabilizing Aurora A kinase, which is achieved through facilitating the chaperonin CCT complex to Aurora A. In addition, CEP55 mutation in Meckel-Gruber syndrome causes the failure of cilia disassembly. Thus, our study establishes a cilia disassembly role for CEP55 in vivo, coupling defects in cilia disassembly to ciliopathy and further suggesting that proper cilia dynamics are critical for mammalian development.

LPA signaling acts as a cell-extrinsic mechanism to initiate cilia disassembly and promote neurogenesis.

Dynamic assembly and disassembly of primary cilia controls embryonic development and tissue homeostasis. Dysregulation of ciliogenesis causes human developmental diseases termed ciliopathies. Cell-intrinsic regulatory mechanisms of cilia disassembly have been well-studied. The extracellular cues controlling cilia disassembly remain elusive, however. Here, we show that lysophosphatidic acid (LPA), a multifunctional bioactive phospholipid, acts as a physiological extracellular factor to initiate cilia disassembly and promote neurogenesis. Through systematic analysis of serum components, we identify a small molecular-LPA as the major driver of cilia disassembly. Genetic inactivation and pharmacological inhibition of LPA receptor 1 (LPAR1) abrogate cilia disassembly triggered by serum. The LPA-LPAR-G-protein pathway promotes the transcription and phosphorylation of cilia disassembly factors-Aurora A, through activating the transcription coactivators YAP/TAZ and calcium/CaM pathway, respectively. Deletion of Lpar1 in mice causes abnormally elongated cilia and decreased proliferation in neural progenitor cells, thereby resulting in defective neurogenesis. Collectively, our findings establish LPA as a physiological initiator of cilia disassembly and suggest targeting the metabolism of LPA and the LPA pathway as potential therapies for diseases with dysfunctional ciliogenesis.

[Distribution characteristics of heavy metals in soil and its influence on greening plants in a main road of Lanzhou City, Northwest China]. / å °å·žå¸‚æŸäº¤é€šå¹²é“åœŸå£¤é‡é‡‘å±žåˆ†å¸ƒç‰¹å¾åŠå ¶å¯¹ç»¿åŒ–æ¤ç‰©çš„å½±å“.

To investigate the characteristics of heavy metal pollution caused by traffic and its potential ecological risks, we measured the amount of metal elements in samples collected from a traffic trunk road in Lanzhou City with atomic absorption spectrophotometer. The single factor index method and potential ecological risk index method were used to evaluate the degree of pollution and potential ecological risks, and then the effects of heavy metal pollution on chlorophyll and calcium (Ca) contents in greening plants were analyzed. The results showed that the amount of heavy metals including chromium (Cr), manganese (Mn), zinc (Zn), copper (Cu) and nickel (Ni) in the soils increased significantly, with Cr, Cu and Pb reaching moderate pollution level. The degree of potential ecological risk was Cu>Pb>Cr>Ni>Zn>Mn. Sophora japonica, Rosa chinesis, Prunus ceraifera, and Euonymus japonicas showed different accumulation effects on Pb, Mn, Zn, and Ni. The content of chlorophyll in the leaves of deciduous species S. japonica, R. chinesis and P. ceraifera was higher in the roadside sampling point than that in the control point, while the pattern was just the opposite in evergreen species E. japonicas and P. orientalis. Foliar Ca content of greening plants in the roadside sampling point was higher than that in the control point, suggesting that high chlorophyll and Ca contents might be beneficial to plant survival in the heavy metal contaminated area. Taken together, traffic operation led to the accumulation of heavy metals (Cr, Mn, Zn, Cu, and Ni) in the soil of the study area. S. japonica, R. chinesis, P. ceraifera and E. japonicas could accumulate Pb, Mn, Zn and Ni, which could be used as greening plants in soils polluted by those heavy metals.

6-Gingerol ameliorates sepsis-induced liver injury through the Nrf2 pathway.

Sepsis-induced liver injury is very common in intensive care units. Here, we investigated the effects of 6-gingerol on sepsis-induced liver injury and the role of the Nrf2 pathway in this process. 6-Gingerol is the principal ingredient of ginger that exerts anti-inflammatory and antioxidant effects. Using cecal ligation and puncture (CLP) to induce polymicrobial sepsis and related liver injury, we found that mice pre-treated with 6-Gingerol showed less incidences of severe liver inflammation and death than untreated CLP groups. 6-Gingerol administration also inhibited the expression of pyroptosis-related proteins, including NOD-like receptor protein 3 (NLRP3), IL-1ß, and caspase-1. Consistent with these findings, 6-gingerol reduced the effects of pyroptosis induced by lipopolysaccharide (LPS) and adenosine 5'-triphosphate (ATP) in RAW 264.7 cells, as evidenced by IL-1ß and caspase-1 protein levels in the supernatant and propidium iodide (PI) staining. 6-Gingerol was shown to activate the Nrf2 pathway in vivo and in vitro. Notably, Nrf2 siRNA transfection nullified the inhibitory effects of 6-gingerol on pyroptosis in vitro. In summary, these findings suggested that 6-gingerol alleviated sepsis-induced liver injury by inhibiting pyroptosis through the Nrf2 pathway.

Geniposide Enhances Macrophage Autophagy through Downregulation of TREM2 in Atherosclerosis.

Macrophage autophagy defect is closely related to the progression of atherosclerosis (AS) and is regulated by the triggering receptor expressed on myeloid cell 2 (TREM2). TREM2 is a key factor in the development of Alzheimer's disease (AD), the deficiency of which leads to anomalous autophagy in microglia. However, the role of TREM2 in the autophagy of plaque macrophages is still unclear. Geniposide (GP) can inhibit AS progression and enhance macrophage autophagy, although the underlying mechanisms remain unknown. We found that high-fat diet (HFD) feeding significantly increased TREM2 levels and inhibited autophagy in the macrophages of ApoE[Formula: see text] mice. TREM2 overexpression in RAW264.7 macrophages decreased autophagy via activation of mTOR signaling. GP inhibited the progression of AS in ApoE[Formula: see text] mice, reinforced macrophage autophagy, and downregulated TREM2 by inhibiting mTOR signaling. Taken together, augmenting the autophagy levels in plaque macrophages by inhibiting the TREM2/mTOR axis can potentially impede atherosclerotic progression. The promising therapeutic effects of GP seen in this study should be validated in future trials, and the underlying mechanisms have to be elucidated in greater detail.

Guillain-Barré syndrome in a patient with multiple myeloma after bortezomib therapy: A case report.

BACKGROUND: Bortezomib is a first-line drug approved for patients with multiple myeloma (MM) and has significantly increased their overall survival. However, bortezomib-induced peripheral neuropathy (PN) remains a significant side effect that has led to its discontinuation in some patients. Guillain-Barré syndrome (GBS) is recognized as an immune-mediated PN characterized by the involvement of multiple nerve roots and peripheral nerves and albuminocytologic dissociation in cerebrospinal fluid (CSF) tests. Intravenous immunoglobulin (IVIG) and plasmapheresis are effective. CASE SUMMARY: A 45-year-old man diagnosed with stage III MM (λ type) was treated with bortezomib and dexamethasone. Fourteen days after the second course, he complained of intense burning sensation in the lower limbs and hands, loss of tactile sensation, and pain in the distal area of both thighs and in the distal part of both wrist joints. Neurological examination revealed absence of knee and ankle reflexes. CSF examination revealed albuminocytologic dissociation. Nerve conduction studies indicated sensory nerve action potential amplitudes, conduction velocity decrease, and F wave latency prolongation. He was diagnosed as MM complicated with GBS. Subsequently, he was treated with high-dose IVIG (400 mg/kg/d for five days). His symptoms fully resolved without relapse at the 6-month follow-up. CONCLUSION: Our case highlights the differential diagnosis and management of complications after bortezomib treatment in MM.

Intranasal co-administration of 1,8-cineole with influenza vaccine provide cross-protection against influenza virus infection.

BACKGROUND: Vaccination is the most efficient means for protection against influenza. However, the various vaccines have low efficacy to protect against pandemic strains because of antigenic drift and recombination of influenza virus. Adjuvant therapy is one of the attempts to improve influenza vaccine effective cross-protection against influenza virus infection. Our previous study confirmed that 1,8-cineole inhibits the NF-κB, reduces pro-inflammatory cytokines, and relieves the pathological changes of viral pneumonia in mice infected with influenza virus. HYPOTHESIS/PURPOSE: 1,8-cineole, administered via intranasal (i.n.) route, may also have the capacity to be an adjuvant of the influenza vaccine. This study was designed to investigate the potential use of i.n. co-administration of 1,8-cineole, a major component of the Eucalyptus essential oils, with influenza vaccine and whether could provide cross-protection against influenza virus infection in a mouse model. STUDY DESIGN: I.n. co-administration of 1,8-cineole in two doses (6.25 and 12.5 mg/kg) with influenza vaccine was investigated in a mouse model in order to see whether it could provide cross-protection against influenza virus infection. METHODS: The mice were intranasally immunized three times at the 0, 7 and 14 day with vaccine containing 0.2 µg hemagglutinin (HA) and/or without 1,8-cineole. Seven days after the 3rd immunization dose, the mice were infected with 50 µl of 15 LD50 (50% mouse lethal dose) influenza virus A/FM/1/47 (H1N1). On day 6 post-infection, 10 mice per group were sacrificed to collect samples, to take the body weight and lung, and detect the viral load, pathological changes in the lungs and antibody, etc. The collected samples included blood serum and nasal lavage fluids. In addition, the survival experiments were carried out  to investigate the survival of mice. RESULTS: Mice i.n. inoculated with influenza vaccine and 12.5 mg/kg 1,8-cineole increased the production of influenza-specific serum immunoglobulin (Ig) G2a antibodies, stimulated mucosal secretive IgA (s-IgA) responses at the nasal cavity, improved the expression of respiratory tract intraepithelial lymphocytes (IELs) in the upper respiratory tract, and promoted dendritic cell (DC) maturation and the expression of co-stimulatory molecules cluster of differentiation (CD)40, CD80 and CD86 in peripheral blood. Importantly, mice that had received 1,8-cineole-supplemented influenza vaccine showed longer survival time, milder inflammation, less weight loss and mortality rate and lower lung index and viral titers compared to that of mice immunized a non-1,8-cineole-adjuvanted split vaccine. Thus, i.n. immunization with 1,8-cineole-adjuvanted vaccine induces a superior cross-protective immunity against infection with influenza than an inactivated vaccine only. CONCLUSION: These results suggest that 1,8-cineole (12.5 mg/kg) has a cross-protection against influenza virus, co-administered with inactivated influenza viral antigen in a mouse model.