Phase 1 single-centre placebo- and etomidate-controlled study in healthy volunteers to assess safety, tolerability, clinical effects, and pharmacokinetics of intravenous methoxyethyl etomidate hydrochloride (ET-26).

Background: Methoxyethyl etomidate hydrochloride (ET-26) is a novel etomidate analogue. This is the first-in-human study of a bolus i.v.

Long-term sciatic nerve block led by a supramolecular arrangement of self-delivery local anesthetic nano systems.

Classical local anesthetics are unsuitable to treat regional pain lasting several days due to their limited duration and systemic toxicity. Self-delivery nano systems without excipients were designed for long-term sensory blocks. 1a self-assembled into different vehicles with different fractions of intermolecular π-π stacking, transported itself into nerve cells, and released single molecules slowly to achieve long-term duration for rats' sciatic nerve block for 11.

A novel homozygous TUB mutation associated with autosomal recessive retinitis pigmentosa in a consanguineous Chinese family.

Background: Retinitis pigmentosa (RP) is the most common type of inherited retinopathy. At least 69 genes for RP have been identified. A significant proportion of RP, however, remains genetically unsolved.

Lido-OH, a Hydroxyl Derivative of Lidocaine, Produced a Similar Local Anesthesia Profile as Lidocaine With Reduced Systemic Toxicities.

lidocaine is one of the most commonly used local anesthetics for the treatment of pain and arrhythmia. However, it could cause systemic toxicities when plasma concentration is raised. To reduce lidocaine's toxicity, we designed a hydroxyl derivative of lidocaine (lido-OH), and its local anesthesia effects and systemic toxicity were quantitively investigated.

Molecular biology of the SARs-CoV-2 spike protein: A review of current knowledge.

The global coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an unprecedented worldwide public health emergency. Despite the concerted efforts of the scientific field, by April 25, 2021, SARS-CoV-2 had spread to over 192 countries/regions, causing more than 146 million confirmed cases including 31 million deaths. For now, an established treatment for patients with COVID-19 remains unavailable.

The Bioequivalence of Emulsified Isoflurane With a New Formulation of Emulsion: A Single-Center, Single-Dose, Double-Blinded, Randomized, Two-Period Crossover Study.

Emulsified isoflurane is a novel intravenous general anesthetic obtained by encapsulating isoflurane molecules into emulsion. The formulation of emulsion has been improved according to the latest regulations of the China Food and Drug Administration. This study was designed to compare the bioequivalence of the new and previous formulation emulsion of isoflurane.

The 14-day repeated-dose toxicity study of a fixed-dose combination, QXOH/levobupivacaine, via subcutaneous injection in beagle dogs.

QXOH-Levobupivacaine (LB) is a fixed-dose combination of 35-mM QXOH and 10-mM LB. It was developed for perioperative analgesia because of its long-acting analgesic effect. The purpose of this study was to evaluate the potential toxicity of QXOH-LB in beagle dogs in accordance with the Guidance on the repeated-dose toxicity published by the China Food and Drug Administration.

Novel compound LL-a produces long and nociceptive-selective regional anesthesia via TRPV1 channels in rodents sciatic nerve block model.

Background And Objective: Long-acting nociceptive-selective regional anesthesia has remained an elusive clinical goal. We aspired to identify a novel compound that would produce nociceptive-selective regional anesthesia through the transient receptor potential vanilloid 1 (TRPV1) channels.

Methods: We designed and synthesized a novel compound (LL-a) that penetrates the cell membrane through TRPV1 channels and binds to voltage-gated sodium channels.

The Preclinical Pharmacological Study of a Novel Long-Acting Local Anesthetic, a Fixed-Dose Combination of QX-OH/Levobupivacaine, in Rats.

Previous studies demonstrated that 35 mM QX-OH/10 mM Levobupivacaine (LL-1), a fixed-dose combination, produced a long-acting effect in rat local anesthesia models. All preclinical pharmacodynamic results indicated that LL-1 had potential for postsurgical pain treatment. The objective of this study was to investigate the pharmacokinetics of LL-1.

A Fixed-Dose Combination, QXOH/Levobupivacaine, Produces Long-Acting Local Anesthesia in Rats Without Additional Toxicity.

QXOH, a QX314 derivative with longer duration and lesser local toxicity, is a novel local anesthetic in preclinical drug development. Previous studies demonstrated that bupivacaine can prolong the effects of QX314. So, we attempted to combine QXOH with levobupivacaine to shorten the onset time and lengthen the duration.

Addition of dexmedetomidine to QX-314 enhances the onset and duration of sciatic nerve block in rats.

An experimental set-up was designed to observe whether adding dexmedetomidine to QX-314 would enhance the onset and duration of sensory and motor function in a rat sciatic nerve block model. Fifty-six Sprague-Dawley rats received unilateral sciatic nerve blocks with 0.2 mL of 35 mmol/L QX-314 alone, dexmedetomidine (5.

Janus particles self-assembled from a small organic atypical asymmetric gemini surfactant.

A series of atypical asymmetric gemini surfactants with an amphiphilic carbonate group (-O-CO-O-) have been prepared. Some of these compounds could self-assemble in water into gourd-shaped Janus particles (JPs). Initial results suggested that the formation of JPs was highly likely to be related to their atypical gemini surfactant structure.

QX-OH, a QX-314 derivative agent, produces long-acting local anesthesia in rats.

QX-314 has been shown to produce long-acting local anesthesia in vivo in animals; however, translation to humans has been impeded by concerns about toxicity. We investigated whether the newly emerged QX-OH molecule could confer long-lasting anesthesia with a low local toxicity in rats. In rat sciatic nerve block model, QX-OH 25mM produced a longer sensory block than QX-314 25mM (median [25th, 75th percentiles], 5.

Correction: The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats.

[This corrects the article DOI: 10.1371/journal.pone.

Evaluation of the cardiotoxicity and resuscitation of rats of a newly developed mixture of a QX-314 analog and levobupivacaine.

Objective: This study was designed to evaluate the cardiotoxicity of a QX-314 analog (QX-OH) and a mixture of QX-OH and levobupivacaine (LL-1) and to compare the ability to resuscitate rats after asystole induced by levobupivacaine (Levo-BUP), QX-314, QX-OH, and LL-1.

Methods: First, we used the "up-and-down" method to determine median dose resulting in appearance of cardiotoxicity (CD) and asystole (CD) of Levo-BUP, QX-314, QX-OH, and LL-1 in rats. Safety index (SI; ratio of CD compared with 2-fold median effective dose needed to produce sensory blockade) of the 4 drugs was calculated.

The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats.

Objective: The quaternary lidocaine derivative (QX-314) in combination with bupivacaine can produce long-lasting nerve blocks in vivo, indicating potential clinical application. The aim of the study was to investigate the efficacy, safety, and the optimal formulation of this combination.

Methods: QX-314 and bupivacaine at different concentration ratios were injected in the vicinity of the sciatic nerve in rats; bupivacaine and saline served as controls (n = 6~10).

Effects of Liposomes Charge on Extending Sciatic Nerve Blockade of N-ethyl Bromide of Lidocaine in Rats.

N-methyl bromide of lidocaine (QX-314) is a potential local anaesthetic with compromised penetration through cell membranes due to its obligated positive charge. Liposomes have been widely used for drug delivery with promising efficacy and safety. Therefore we investigated the local anaesthetic effects and tissue reactions of QX-314 in combination with anionic, cationic or neutral liposomes in rat sciatic nerve block model, and explored the effects of these liposomes on cellular entry of QX-314 in human embryonic kidney 293 cells.

OVA12, a novel tumor antigen, promotes cancer cell growth and inhibits 5-fluorouracil-induced apoptosis.

To achieve a better understanding of mechanisms that underlie carcinogenesis and to identify novel target molecules for diagnosis and therapy of carcinoma, we previously identified 24 distinct gene clones by immunoscreening of a cDNA library derived from an ovarian cancer patient through SEREX analysis. Among these genes we focused on a novel gene termed OVA12 and which putatively encodes a 114-amino-acid protein. In the present study, we found that OVA12 was ubiquitously overexpressed in diverse human tumor cell lines.

OVA66 increases cell growth, invasion and survival via regulation of IGF-1R-MAPK signaling in human cancer cells.

Ovarian cancer-associated antigen 66 (OVA66), also known as CML66 (GenBank Accession No. AF283301), was first identified in an ovarian carcinoma complementary DNA (cDNA) expression library and was shown to play a role in tumorigenesis. Here, we find that OVA66 influences tumorigenesis by regulating the type I insulin-like growth factor receptor (IGF-1R) signaling pathway.

OVA66, a tumor associated protein, induces oncogenic transformation of NIH3T3 cells.

The tumor associated antigen OVA66 has been demonstrated to be highly expressed in malignant tumors and implicated in various cellular processes. To further elucidate its oncogenic character, we established an OVA66 stably overexpressed NIH3T3 cell line and a vector transfected control, named NIH3T3-flagOVA66 and NIH3T3-mock, respectively. NIH3T3-flagOVA66 cells showed faster cell cycling, proliferation, cell migration and more resistance to 5-fluorouracil-induced apoptosis.

Transdermal anaesthesia with lidocaine nano-formulation pretreated with low-frequency ultrasound in rats model.

Rapid local transdermal anaesthetic is desirable in clinic. In this paper, lidocaine loaded poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) nanoparticles were prepared, and a novel transdermal lidocaine formulation: lidocaine loaded PCL-PEG-PCL nanoparticles in F127 hydrogel (Nano-Lido Gel), was demonstrated. These lidocaine loaded PCL-PEG-PCL nanoparticles with mean particle size of ca.

Biodegradable in situ gel-forming controlled drug delivery system based on thermosensitive PCL-PEG-PCL hydrogel. Part 2: sol-gel-sol transition and drug delivery behavior.

In this work, a biodegradable and injectable in situ gel-forming controlled drug delivery system based on thermosensitive poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCEC) hydrogel was studied. The prepared PCEC hydrogel undergoes temperature-dependent sol-gel-sol transition, which is a flowing sol at ambient temperature and turns into a non-flowing gel at around physiological body temperature. Furthermore, the sol-gel phase transition mechanism was investigated using (13)C-nuclear magnetic resonance imaging and a laser diffraction particle size analyzer.

[The progress of research on low-frequency sonophoresis and its applications].

Low-frequency ultrasound can increase the transdermal delivery of many drugs, including macromolecular drugs. The main mechanism is ultrasonic cavitation. Most researchers pointed out that it could change the form-structure of stratum corneum keratinocytes and, in this way, it can improve the permeability of skin.