Exosomes derived from human urine-derived stem cells ameliorate IL-1β-induced intervertebral disk degeneration.

Background: Human intervertebral disk degeneration (IVDD) is a sophisticated degenerative pathological process. A key cause of IVDD progression is nucleus pulposus cell (NPC) degeneration, which contributes to excessive endoplasmic reticulum stress in the intervertebral disk. However, the mechanisms underlying IVDD and NPC degeneration remain unclear.

The first nano-cocrystal formulation of marine drug cytarabine with uracil based on cocrystal nanonization strategy for long-acting injection exhibiting enhanced antitumor activity.

To emphasize the superiority of uracil (UR) in ameliorating biopharmaceutical characteristics of marine antitumor medicine cytarabine (ARA), thus gaining some innovative opinions for the exploitation of nanococrystal formulation, a cocrystal nanonization strategy is proposed by integrating cocrystallization and nanosize preparation techniques. For one thing, based on UR's unique structural features and natures together with advantages of preferential uptake by tumor cells, cocrystallizing ARA with UR is expected to improve the in vitro/vivo performances. For another, the nanonization procedure is oriented towards maintaining the long-term effective drug level.

Correction: Supramolecular self-assembly of amantadine hydrochloride with ferulic acid dual optimization strategy establishes a precedent of synergistic antiviral drug-phenolic acid nutraceutical cocrystal.

Correction for 'Supramolecular self-assembly of amantadine hydrochloride with ferulic acid dual optimization strategy establishes a precedent of synergistic antiviral drug-phenolic acid nutraceutical cocrystal' by Ling-Yang Wang , , 2021, , 3988-3999, https://doi.org/10.1039/D1AN00478F.

Cocrystallization-Driven Double-Optimized Stratagem toward Directional Self-Assembly for the First Ternary Salt Cocrystal of Cardiotonic Drug Milrinone with Different Phenolic Acids Exhibits Optimal / Biopharmaceutical Peculiarities.

The current research leverages the structural features and property superiorities along with benefits in protecting cardiovascular system of gallic acid (GLC) and gentisic acid (HGA) to optimize / peculiarities of cardiotonic drug milrinone (MIL) through developing a stratagem of cocrystallization-driven double-optimized ternary salt cocrystal. This strategy assembles MIL ternary salt cocrystal by shaping a cocrystallization moiety relying on noncovalent interplays with GLC to obtain permeability advancement and molding a salt segment via the salification of proton transfer between HGA and MIL molecules to facilitate solubility enhancement. While the ameliorative properties further modulate the pharmacokinetic behaviors, thus fulfilling a dual optimization of MIL's biopharmaceutical characteristics on both and aspects.

Microfibrillar-associated protein 5 suppresses adipogenesis by inhibiting essential coactivator of PPARγ.

Femoral head necrosis is responsible for severe pain and its incidence is increasing. Abnormal adipogenic differentiation and fat cell hypertrophy of bone marrow mesenchymal stem cells increase intramedullary cavity pressure, leading to osteonecrosis. By analyzing gene expression before and after adipogenic differentiation, we found that Microfibril-Associated Protein 5 (MFAP5) is significantly down-regulated in adipogenesis whilst the mechanism of MFAP5 in regulating the differentiation of bone marrow mesenchymal stem cells is unknown.

5-fluorouracil-caffeic acid cocrystal delivery agent with long-term and synergistic high-performance antitumor effects.

To explore how to transform cocrystals of the anticancer drug 5-fluorouracil (FL) with caffeic acid (CF; FL-CF-2HO) into a nanoformulation, a self-assembly strategy of cocrystal-loaded micelles is proposed. Nanomicelles were assembled to deliver cocrystal FL-CF-2HO with synergistic activity, and their / properties were evaluated by combining theoretical and experimental methods. More cocrystal was packed into the polymers due to the stronger interaction energy during micellar assembly, producing excellent cytotoxicity and pharmacokinetic behavior, especially synergistic abilities and long-term therapy.

The first marine dual-drug cocrystal of cytarabine with 5-fluorouracil having synergistic antitumor effects shows superior biopharmaceutical peculiarities by oral administration.

In order to highlight the advantages of cocrystallization technique in perfecting in vitro/vivo natures of marine drug cytarabine (ARC), and fill the gap of the research of marine pharmaceutical cocrystals with synergistic antitumor effects, the first dual-drug cocrystal simultaneously containing ARC and antitumor drug 5-fluorouracil (FU), viz. ARC-FU, is successfully designed and assembled. The accurate structure is perfectly resolved by single-crystal X-ray diffraction and other approaches.

[Experience of Community-based Home Hospice Care Practice for 24 Patients in Beijing Puhuangyu Community].

Objective To investigate the feasibility of home hospice care based on the practical experience in Puhuangyu community of Beijing.Methods We selected the patients assessed by hospice care team and receiving home hospice care from Puhuangyu Community Health Service Center of Beijing from January 1,2020 to December 31,2021.The clinical manifestations,hospice services received,and place of death of the patients were analyzed.

[Community-based Home Hospice Care Model under the Guidance of Tertiary Hospitals].

Community-based home hospice care provided by community service centers and family physician teams aims to alleviate the suffering of terminally ill patients and help them to receive end-of-life care and pass away at home.The Puhuangyu Community Health Service Center established the home hospice care model of PUMCH-Puhuangyu Coordination at the end of 2019.The model has been practiced and improved to date.

miR-219a-5p inhibits the pyroptosis in knee osteoarthritis by inactivating the NLRP3 signaling via targeting FBXO3.

Purpose: This work was to identify the function and mechanism of miR-219a-5p in regulating knee osteoarthritis (KOA).

Methods: Rat fibroblast-like synoviocytes (FLSs) were isolated to construct KOA cell model by lipopolysaccharide and adenosine triphosphate treatment. miR-219a-5p and FBXO3 expression in FLSs was modulated by transfection.

Governing effects of melt viscosity on fire performances of polylactide and its fire-retardant systems.

Extreme flammability of polylactide (PLA) has restricted its real-world applications. Traditional research only focuses on developing new effective fire retardants for PLA without considering the effect of melt viscosity on its fire performances. To fill the knowledge gap, a series of PLA matrices of varied melt flow index (MFI) with and without fire retardants are chosen to examine how melt viscosity affects its fire performances.

A novice cocrystal nanomicelle formulation of 5-fluorouracil with proline: The design, self-assembly and in vitro/vivo biopharmaceutical characteristics.

To fully play the advantages of cocrystallization and nano-preparation techniques in regulating in vitro/vivo biopharmaceutical properties of anticancer drug 5-fluorouracil (FU), and further exploit new avenues in its formulation development, a recombination strategy of cocrystallization and nano-micellar self-assembly techniques is proposed. Thereinto, the cocrystallization technique is aiming at augmenting antitumor ability by ameliorating physicochemical performances of FU, while the nano-micellar self-assembly technique is mainly employed to achieve slowed release and long-term efficacy. Guided by this strategy, a new zwitterionic cocrystal of FU with L-proline (PL), FU-PL, is successfully synthesized, and then incorporated into carriers PEG-PCL to gain cocrystal micelles.

Dok5 regulates proliferation and differentiation of osteoblast via canonical Wnt/β-catenin signaling.

Objective: In bone tissue engineering, the use of osteoblastic seed cells has been widely adopted to mediate the osteogenic differentiation so as to prompt bone regeneration and repair. It is hypothesized that Dok5 can regulate the proliferation and differentiation of osteoblasts. In this study, the role of Dok5 in osteoblast proliferation and differentiation was investigated.

Thrap3 promotes osteogenesis by inhibiting the degradation of Runx2.

The dysfunction of osteogenesis is a key character in the pathogenesis of osteoporosis, but the network of signaling mechanisms in controlling the differentiation of osteoblast remain unclear. Thrap3 has been proved participating in various biological process, especially in the differentiation of stem cells. Here, we demonstrate that Thrap3 could promote osteogenesis through the inhibition of the degradation of Runx2, which is a key molecular structure in early osteoblast differentiation.

Quantifying the Effects of Medical Examination and Possible Risk Factors against the Incidence of Cervical Cancer in a Low Human Papillomavirus Vaccination Coverage: An Ecological Study in Japan.

Cervical cancer (CC) is one of the most common gynecological malignancies in females, mainly caused by human papillomavirus (HPV). In countries with lower HPV vaccine coverage, such as Japan, medical examination may play a key role in decreasing CC incidence. This study aimed to quantify the effect of medical examination on cervical cancer (CC) incidence in Japan, considering the effects of possible risk factors.

IARS2 regulates proliferation, migration, and angiogenesis of human umbilical vein endothelial cells.

Objective: In this study, we aimed at investigating the role of isoleucyl-tRNA synthetase in the growth, migration, and angiogenesis of human umbilical vein endothelial cells and the underlying molecular mechanism.

Methods: To assess the role of isoleucyl-tRNA synthetase, we silenced isoleucyl-tRNA synthetase in human umbilical vein endothelial cells using lentiviral 2 specific short hairpin RNAs (short hairpin RNAs 1 and 2) and examined silencing efficiency using real time quantitative polymerase chain reaction and western blot analyses. Short hairpin RNAs 1-isoleucyl-tRNA synthetase had greater knockdown efficiency, it was used in the entire downstream analysis.

A novel crystalline molecular salt of sulfamethoxazole and amantadine hybridizing antiviral-antibacterial dual drugs with optimal in vitro/vivo pharmaceutical properties.

In order to exploit the advantages to the full of multidrug salification strategy in amending the pharmaceutical properties of drugs both in vitro and in vivo, and further to open up a new way for its applications in bacteria-virus mixed cross-infection drugs, a novel dual-drug crystalline molecular salt hybridizing antibacterial drug sulfamethoxazole (SFM) with antiviral ingredient amantadine (ATE), namely SFM-ATE, is successfully designed and synthesized via multidrug salification strategy oriented by proton exchange reaction. The crystal structure of the firstly obtained molecular salt is precisely identified by employing single-crystal X-ray diffraction and multiple other techniques. The results show that, in the crystal lattice of molecular salt SFM-ATE, the classical hydrogen bonds together with charge-assisted hydrogen bonds contribute to two- dimensional networks, between which the hydrophobic interaction plays an important role.

Supramolecular self-assembly of amantadine hydrochloride with ferulic acid dual optimization strategy establishes a precedent of synergistic antiviral drug-phenolic acid nutraceutical cocrystal.

To display the capability of the phenolic acid nutraceutical ferulic acid (FLA) in optimizing the in vitro/in vivo properties of the antiviral drug amantadine hydrochloride (AMH) and achieve synergistically enhanced antiviral effects, thereby gaining some new insights into pharmaceutical cocrystals of antiviral drugs with phenolic acid nutraceuticals, a cocrystallization strategy of dual optimization was created. Based on this strategy, the first drug-phenolic acid nutraceutical cocrystal of AMH with FLA, namely AMH-FLA-H2O, was successfully assembled and completely characterized by employing single-crystal X-ray diffraction and other analytical techniques. The cocrystal was revealed to be composed of AMH, FLA, and water molecules in the ratio of 3 : 1 : 1.

Supramolecular self-assembly and perfected / property of 5-fluorouracil and ferulic acid on the strength of double optimized strategy: the first 5-fluorouracial-phenolic acid nutraceutical cocrystal with synergistic antitumor efficacy.

For highlighting the predominance of phenolic acid nutraceutical ferulic acid (FR) in regulating the in vivo/vitro performances of anticancer drug 5-fluorouracil (Flu) and strengthening their cooperativity in antitumor effect, thus achieving a major breakthrough in the development of drug-nutraceutical cocrystal with synergistic antitumor action, a cocrystallization strategy of dual optimization is created, in which both the in vivo and vitro natures of Flu are improved by exploiting the FR's excellent physicochemical property. Moreover, Flu's anticancer effects were promoted by exerting the assistant antitumor peculiarity of FR. Such dual optimization of FR for Flu in physicochemical properties and anticancer activities is beneficial for realizing synergistic augmentation effect by taking the benefit of the cooperativeness of Flu and FR in the anticancer ability.

Effect of combined treatment with pulsed electromagnetic field stimulation and sclerostin monoclonal antibody on changes in bone metabolism and pedicle screw augmentation in rabbits with ovariectomy-induced osteoporosis.

Background: Both pulsed electromagnetic field (PEMF) stimulation and sclerostin monoclonal antibody are useful for treating osteoporosis, but whether the two therapies have synergistic effects on both screw fixation quality and bone metabolism of ovariectomy-induced osteoporosis has not been reported.

Methods: We used ovariectomy to create a rabbit model of postmenopausal osteoporosis. Then, specimens were fixed with pedicle screws in the L4 vertebral body.

ATP-binding cassette g1 regulates osteogenesis via Wnt/β-catenin and AMPK signaling pathways.

The dysfunction of bone marrow mesenchymal stem cells (BMSCs) in balancing osteogenesis and adipogenesis plays an important role in the occurrence and development of osteoporosis. It's still unknown that whether ATP-binding cassette g1 (Abcg1), a well-proved regulation gene of adipogenesis, regulates osteogenesis. In our previous study, we identified 30 differentially expressed genes in osteogenesis and found the expression level ofAbcg1 negatively related to osteogenesis among these genes.

LncRNA AWPPH is downregulated in osteoporosis and regulates type I collagen α1 and α2 ratio.

Normal ratio of type I collagen α1 to α2 (2:1) maintains normal bone microarchitecture. Altered ratios lead to formation of collagen homotrimers and deteriorated bone microarchitecture. In this study, we aimed to investigate the role of lncRNA AWPPH in osteoporosis.

EDA2R mediates podocyte injury in high glucose milieu.

EDA2R is a member of the large family of tumor necrosis factor receptor (TNFR). Previous studies suggested that EDA2R expression might be increased in the kidneys of diabetic mice. However, its mRNA and protein expression in kidneys were not analyzed; moreover, its role in the development of diabetic kidney disease was not explored.

Protoporphyrin IX-loaded laminarin nanoparticles for anticancer treatment, their cellular behavior, ROS detection, and animal studies.

Laminarin conjugate-based nano-scaled particles were in this study proposed as a delivery system for protoporphyrin IX (Pp IX) in photodynamic therapy (PDT) of human breast cancer cells (MCF-7). Hematin-Laminarin-Dithiodipropionic Acid-MGK, named as HLDM, was an amphiphilic carrier material with dual pH/redox sensitive that could be used to load hydrophobic drug to improve their solubility and enhance biocompatibility. Therefore, we combined photosensitizer (Pp IX) with HLDM to fabricate a novel nano-micelles, herein called Pp IX-loaded HLDM micelles.