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This study aimed to investigate the efficacy and safety of trigeminal parasympathetic pathway (TPP) stimulation in the treatment of dry eye. A comprehensive search for randomized clinical trials was performed in seven databases (MEDLINE, Embase, CENTRAL, etc.) up to 28 February 2023. After screening the suitable studies, the data were extracted and transformed as necessary. Data synthesis and analysis were performed using Review Manager 5.4, and the risk of bias and quality of evidence were evaluated with the recommended tools. Fourteen studies enrolling 1714 patients with two methods (electrical and chemical) of TPP stimulation were included. Overall findings indicate that TPP stimulation was effective in reducing subjective symptom score (standardized mean difference [SMD], -0.45; 95% confidence interval [CI], -0.63 to -0.28), corneal fluorescence staining (mean difference [MD], -0.78; 95% CI, -1.39 to -0.18), goblet cell area (MD, -32.10; 95% CI, -54.58 to -9.62) and perimeter (MD, -5.90; 95% CI, -10.27 to -1.53), and increasing Schirmer's test score (SMD, 0.98; 95% CI, 0.65 to 1.31) and tear film break-up time (SMD, 0.57; 95% CI, 0.19 to 0.95). Compared to inactive or low-activity stimulation controls, it has a higher incidence of adverse events. Therefore, TPP stimulation may be an effective treatment for dry eye, whether electrical or chemical. Adverse events are relatively mild and tolerable. Due to the high heterogeneity and low level of evidence, the current conclusions require to be further verified., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

The iron ion in industrial circulating cooling water is an important indicator for early warning of equipment corrosion and control level. It is interesting to construct an upconversion luminescence iron ion nanoprobe with a common inorganic phosphate water treatment agent. Herein, inorganic phosphate sodium hexametaphosphate (SHMP) was used to regulate the morphology and functionalization of NaYF 4 :Yb 3+ , Er 3+ upconversion luminescent nanoprobe (UCNPs) and applied to fluorometric detection of trace Fe(III) in water based on the fluorescence quenching which is caused by the selective coordination between hexametaphosphate on the surface of UCNPs and Fe(III). The structure, morphology, and luminous intensity of UCNPs were regulated by disodium hydrogen phosphate (ADSP), sodium tripolyphosphate (STPP) and sodium hexametaphosphate(SHMP). The UCNPs functionalized with SHMP has high sensitivity and selectivity for Fe(III) detection. The linear range and detection limit are 1.0-50 μM and 0.2 μM, respectively. The method has satisfactory results for the detection of trace Fe(III) in industrial circulating cooling water., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The oral cavity is an important window for microbial communication between the environment and the human body. The oral microbiome plays an important role in human health. However, compared to the gut microbiome, the oral microbiome has been poorly explored. Here, we analyzed 404 datasets from human oral saliva samples published by the Earth Microbiome Project (EMP) and compared them with 815 samples from the human gut, nose/pharynx, and skin. The diversity of the human saliva microbiome varied significantly among individuals, and the community compositions were complex and diverse. The saliva microbiome showed the lowest species diversity among the four environment types. Human oral habitats shared a small core bacterial community containing only 14 operational taxonomic units (OTUs) under 5 phyla, which occupied over 75% of the sequence abundance. For the four habitats, the core taxa of the saliva microbiome had the greatest impact on saliva habitats than other habitats and were mostly unique. In addition, the saliva microbiome showed significant differences in the populations of different regions, which may be determined by the living environment and lifestyle/dietary habits. Finally, the correlation analysis showed high similarity between the saliva microbiome and the microbiomes of Aerosol (non-saline) and Surface (non-saline), i.e., two environment types closely related to human, suggesting that contact and shared environment being the driving factors of microbial transmission. Together, these findings expand our understanding of human oral diversity and biogeography., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Feng, Zhu, Li, Wang and Chi.)

Traditional detection methods to detect heavy metal ions are time-consuming, complicated, and expensive. Here, we developed a simple electroless plating method to prepare three-dimensional gold nanowire (Au NW) films with high specific surface area. In an aqueous plating bath, tetrachloroauric acid, 4-dimethylaminopyridine and formaldehyde are used as precursor, ligand, and reducing agent, respectively. An electrochemical sensor based on a Au NWs/SPE could be applied for simultaneous detection of lead (Pb(II)), arsenic (As(III)), and mercury (Hg(II)) ions. The detection limits of Pb(II), As(III), and Hg(II) are 2.6, 1.5, and 4.2 μg L -1 , all lower than the permissible limits of the WHO for drinking water (the permissible level of Pb(II) and As(III) is 10.0 μg L -1 , and the permissible level of Hg(II) is 6.0 μg L -1 ), respectively. This work presents a simple and novel method to prepare gold nanowires for quick detection of trace heavy metal ions.

Inhibition of O-GlcNAcase (OGA) has emerged as a promising therapeutic approach to treat tau pathology in neurodegenerative diseases such as Alzheimer's disease and progressive supranuclear palsy. Beginning with carbohydrate-based lead molecules, we pursued an optimization strategy of reducing polar surface area to align the desired drug-like properties of potency, selectivity, high central nervous system (CNS) exposure, metabolic stability, favorable pharmacokinetics, and robust in vivo pharmacodynamic response. Herein, we describe the medicinal chemistry and pharmacological studies that led to the identification of (3a R ,5 S ,6 S ,7 R ,7a R )-5-(difluoromethyl)-2-(ethylamino)-3a,6,7,7a-tetrahydro-5 H -pyrano[3,2- d ]thiazole-6,7-diol 42 (MK-8719), a highly potent and selective OGA inhibitor with excellent CNS penetration that has been advanced to first-in-human phase I clinical trials.

The redesign of the previously reported thiophene-3-yl-methyl urea series, as a result of potential cardiotoxicity, was successfully accomplished, resulting in the identification of a novel potent series of CCR5 antagonists containing the imidazolidinylpiperidinyl scaffold. The main redesign criteria were to reduce the number of rotatable bonds and to maintain an acceptable lipophilicity to mitigate hERG inhibition. The structure-activity relationship (SAR) that was developed was used to identify compounds with the best pharmacological profile to inhibit HIV-1. As a result, five advanced compounds, 6d, 6e, 6i, 6h, and 6k, were further evaluated for receptor selectivity, antiviral activity against CCR5 using (R5) HIV-1 clinical isolates, and in vitro and in vivo safety. On the basis of these results, 6d and 6h were selected for further development.

Basic fibroblast growth factor (bFGF) plays an important role in tumor angiogenesis. Several studies have reported that bFGF may influence cell apoptosis through different signaling pathways. The aim of the present investigation was to study the effect of bFGF on the activities of protein kinase B (PKB)/survivin and cell apoptosis in hepatocellular carcinoma cells (Bel-7402). We treated Bel-7402 cells with bFGF and wortmannin [phosphatidylinositol 3-kinase (PI3K)-specific inhibitor] separately to observe the expression of PKB and survivin detected with RT-PCR and western blotting. The cell cycle and apoptosis were assayed with flow cytometry. We found a significant increase in PKB expression in the group treated with 25 ng/ml bFGF for 10 min (P<0.05), and this effect was significantly inhibited by pretreatment with wortmannin (200 nM) for 1 h. After treatment with 10 ng/ml bFGF, the expression of survivin mRNA in Bel-7402 cells increased significantly, and reached the peak at 16 h (P<0.05); however, this effect could be significantly inhibited by pretreatment with wortmannin (200 mM) in a time-dependent manner. Following incubation with 25 ng/ml bFGF for 10 min, the apoptosis rate and M phase were significantly decreased and S phase cells increased compared with the wortmannin (200 nM)-treated group. When this group was pretreated with wortmannin (200 nM) for 1 h, the apoptosis rate and S phase were significantly increased, M phase cells decreased. The results revealed that wortmannin could induce high apoptosis rates in hepatocellular carcinoma cells, and bFGF could inhibit the cell apoptosis induced by wortmannin. These findings indicate that bFGF could rapidly activate the PKB activities, enhance the expression of survivin and the proliferation of hepatocellular carcinoma cells via the PI3K pathway, thus it may serve as a novel molecule for early targeting therapy of hepatocellular carcinoma.

A series of CCR5 antagonists were optimized for potent inhibition of R5 HIV-1 replication in peripheral blood mononuclear cells. Compounds that met acceptable ADME criteria, selectivity, human plasma protein binding, potency shift in the presence of α-glycoprotein were evaluated in rat and dog pharmacokinetics., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Gold(III) compounds have been examined for potential anti-cancer activity. It is proposed that the molecular targets of these compounds are thiol-containing biological molecules such as the cathepsin cysteine proteases. These enzymes have been implicated in many diseases including cancer. The catalytic mechanism of the cathepsin cysteine proteases is dependent upon a cysteine at the active site which is accessible to the interaction of thiophilic metals such as gold. The synthesis and biological activity of square-planar six-membered cycloaurated Au(III) compounds with a pyridinyl-phenyl linked backbone and two monodentate or one bidentate leaving group is described. Gold(III) cycloaurated compounds were able to inhibit both cathepsins B and K. Structure/activity was investigated by modifications to the pyridinyl-phenyl backbone, and leaving groups. Optimal activity was seen with substitution at the 6 position of the pyridine ring. The reversibility of inhibition was tested by reactivation in the presence of cysteine with a bidentate thiosalicylate compound being an irreversible inhibitor. Five compounds were evaluated for in vitro cytotoxicity against a panel of human tumor cell lines. The thiosalicylate compound was tested in vivo against the HT29 human colon tumor xenograft model. A modest decrease in tumor growth was observed compared with the untreated control tumor., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Voltage-gated ion channels are implicated in pain sensation and transmission signaling mechanisms within both peripheral nociceptors and the spinal cord. Genetic knockdown and knockout experiments have shown that specific channel isoforms, including Na(V)1.7 and Na(V)1.8 sodium channels and Ca(V)3.2 T-type calcium channels, play distinct pronociceptive roles. We have rationally designed and synthesized a novel small organic compound (Z123212) that modulates both recombinant and native sodium and calcium channel currents by selectively stabilizing channels in their slow-inactivated state. Slow inactivation of voltage-gated channels can function as a brake during periods of neuronal hyperexcitability, and Z123212 was found to reduce the excitability of both peripheral nociceptors and lamina I/II spinal cord neurons in a state-dependent manner. In vivo experiments demonstrate that oral administration of Z123212 is efficacious in reversing thermal hyperalgesia and tactile allodynia in the rat spinal nerve ligation model of neuropathic pain and also produces acute antinociception in the hot-plate test. At therapeutically relevant concentrations, Z123212 did not cause significant motor or cardiovascular adverse effects. Taken together, the state-dependent inhibition of sodium and calcium channels in both the peripheral and central pain signaling pathways may provide a synergistic mechanism toward the development of a novel class of pain therapeutics., (Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

A novel series of CXCR4 antagonists were identified based on the substantial redesign of AMD070. These compounds possessed potent anti-HIV-1 activity and showed excellent pharmacokinetics in rat and dog., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

An early lead from the AMD070 program was optimized and a structure-activity relationship was developed for a novel series of heterocyclic containing compounds. Potent CXCR4 antagonists were identified based on anti-HIV-1 activity and Ca(2+) flux inhibition that displayed good pharmacokinetics in rat and dog., (Copyright © 2010 Elsevier Ltd. All rights reserved.)