Biodegradable copper-containing mesoporous microspheres loaded with ginsenoside Rb1 for infarcted heart repair.

The current unavailability of efficient myocardial repair therapies constitutes a significant bottleneck in the clinical management of myocardial infarction (MI). Ginsenoside Rb1 (GRb1) has emerged as a compound with potential benefits in safeguarding myocardial cells and facilitating the regeneration of myocardial tissue. However, its efficacy in treating MI-related ischemic conditions is hampered by its low bioavailability and inadequate angiogenic properties.

Strontium zinc silicate simultaneously alleviates osteoporosis and sarcopenia in tail-suspended rats via Piezo1-mediated Ca signaling.

Background: Long-term physical inactivity probably leads to a co-existence of osteoporosis and sarcopenia which result in a high risk of falls, fractures, disability and even mortality. However, universally applicable and feasible approaches are lacking in the concurrent treatment of osteoporosis and sarcopenia. In this study, we evaluated the effect of strontium zinc silicate bioceramic (SZS) extract on osteoporosis and sarcopenia and explored its underlying mechanisms.

Ion cocktail therapy for myocardial infarction by synergistic regulation of both structural and electrical remodeling.

Myocardial infarction (MI) is a leading cause of death worldwide. Few drugs hold the ability to depress cardiac electrical and structural remodeling simultaneously after MI, which is crucial for the treatment of MI. The aim of this study is to investigate an effective therapy to improve both electrical and structural remodeling of the heart caused by MI.

pH-Responsive Wound Dressing Based on Biodegradable CuP Nanozymes for Treating Infected and Diabetic Wounds.

Nanozymes, emerging nanomaterials for wound healing, exhibit enzyme-like activity to modulate the levels of reactive oxygen species (ROS) at wound sites. Yet, the solo regulation of endogenous ROS by nanozymes often falls short, particularly in chronic refractory wounds with complex and variable pathological microenvironments. In this study, we report the development of a multifunctional wound dressing integrating a conventional alginate (Alg) hydrogel with a newly developed biodegradable copper hydrogen phosphate (CuP) nanozyme, which possesses good near-infrared (NIR) photothermal conversion capabilities, sustained Cu ion release ability, and pH-responsive peroxidase/catalase-mimetic catalytic activity.

3D-printed GelMA/CaSiO composite hydrogel scaffold for vascularized adipose tissue restoration.

The increased number of mastectomies, combined with rising patient expectations for cosmetic and psychosocial outcomes, has necessitated the use of adipose tissue restoration techniques. However, the therapeutic effect of current clinical strategies is not satisfying due to the high demand of personalized customization and the timely vascularization in the process of adipose regeneration. Here, a composite hydrogel scaffold was prepared by three-dimensional (3D) printing technology, applying gelatin methacrylate anhydride (GelMA) as printing ink and calcium silicate (CS) bioceramic as an active ingredient for breast adipose tissue regeneration.

Zn SiO Bioceramic Attenuates Cardiac Remodeling after Myocardial Infarction.

In the pursuit of therapeutic strategies for myocardial infarction (MI), a pivotal objective lies in the concurrent restoration of blood perfusion and reduction of cardiomyocyte apoptosis. However, achieving these dual goals simultaneously presents a considerable challenge. In this study, a Zn SiO bioceramic capable of concurrently sustaining the release of bioactive SiO and Zn ions, which exhibit a synergistic impact on endothelial cell angiogenesis promotion, cardiomyocyte apoptosis inhibition, and myocardial mitochondrial protection against oxygen-free radical (reactive oxygen species) induced injury is developed.

Silicate ions as soluble form of bioactive ceramics alleviate aortic aneurysm and dissection.

Aortic aneurysm and dissection (AAD) are leading causes of death in the elderly. Recent studies have demonstrated that silicate ions can manipulate multiple cells, especially vascular-related cells. We demonstrated in this study that silicate ions as soluble form of bioactive ceramics effectively alleviated aortic aneurysm and dissection in both Ang II and β-BAPN induced AAD models.

Silicate Ions Derived from Calcium Silicate Extract Decelerate Ang II-Induced Cardiac Remodeling.

Background: Pathological cardiac hypertrophy is one of the main activators of heart failure. Currently, no drug can completely reverse or inhibit the development of pathological cardiac hypertrophy. To this end, we proposed a silicate ion therapy based on extract derived from calcium silicate (CS) bioceramics for the treatment of angiotensin II (Ang II) induced cardiac hypertrophy.

3D printed strontium-zinc-phosphate bioceramic scaffolds with multiple biological functions for bone tissue regeneration.

Calcium phosphate (CaP) bioceramics are broadly employed for bone regeneration due to their excellent biocompatibility and osteoconductivity. However, they are not capable of repairing healing-impaired bone defects such as defects with conditions of ischemia or infection due to restricted bioactivities. In this study, we synthesized single-phased strontium-zinc-phosphate (SZP, SrZn(PO)) bioceramics a solution combustion method and further fabricated SZP scaffolds using a three-dimensional (3D) printing technique.

Mild Heat-Assisted Polydopamine/Alginate Hydrogel Containing Low-Dose Nanoselenium for Facilitating Infected Wound Healing.

In clinical practice, it has become urgent to develop multifunctional wound dressings that can combat infection and prompt wound healing simultaneously. In this study, we proposed a polydopamine/alginate/nanoselenium composite hydrogel (Alg-PDA-Se) for the treatment of infected wounds. In particular, polydopamine endows the composite hydrogel with controllable near-infrared photothermal properties, while low-dosage selenium nanoparticles (Se NPs) offer excellent anti-oxidation, anti-inflammatory, pro-proliferative, pro-migration, and pro-angiogenic performances, which are verified by multiple cells, including macrophages, fibroblasts, and endothelial cells.

A combination therapy for androgenic alopecia based on quercetin and zinc/copper dual-doped mesoporous silica nanocomposite microneedle patch.

A nanocomposite microneedle (ZCQ/MN) patch containing copper/zinc dual-doped mesoporous silica nanoparticles loaded with quercetin (ZCQ) was developed as a combination therapy for androgenic alopecia (AGA). The degradable microneedle gradually dissolves after penetration into the skin and releases the ZCQ nanoparticles. ZCQ nanoparticles release quercetin (Qu), copper (Cu) and zinc ions (Zn) subcutaneously to synergistically promote hair follicle regeneration.

Dissolvable hyaluronic acid microneedles loaded with β-Elemene for the treatment of psoriasis.

The pathology of psoriasis involves the over-proliferation of keratinocytes, exaggerated inflammation of keratinocytes, and infiltration of inflammatory cells such as macrophages (Mø), The therapeutic outcomes of current treatment targeting one single pathological process are less than satisfactory. Based on their diverse biological activities, natural products offer a potential solution to this problem. In this study, we investigated the effects of β-Elemene (ELE) on both psoriatic keratinocytes and M1-type Mø (M1-Mø) .

Substitution of SERCA2 Cys aggravates cardiac fibrosis by promoting the transformation of cardiac fibroblasts to cardiac myofibroblasts.

Sarcoplasmic/endoplasmic reticulum Ca ATPase 2 (SERCA2) is vital to maintain intracellular calcium homeostasis, and its redox Cys (C674) is the key to regulating activity. Our goal was to investigate whether the redox state of SERCA2 C674 is critical for cardiac fibrosis and the mechanisms involved. Heterozygous SERCA2 C674S knock-in (SKI) mice, in which half of C674 was substituted by serine, were used to mimic the partial loss of the reactive C674 thiol in pathological conditions.

Multi-functional wound dressings based on silicate bioactive materials.

Most traditional wound dressings passively offer a protective barrier for the wounds, which lacks the initiative in stimulating tissue regeneration. In addition, cutaneous wound healing is usually accompanied by various complicated conditions, including bacterial infection, skin cancer, and damaged skin appendages, bringing further challenges for wound management in clinic. Therefore, an ideal wound dressing should not only actively stimulate wound healing but also hold multi-functions for solving problems associated with different specific wound conditions.

Inactivation of SERCA2 Cys accelerates aortic aneurysms by suppressing PPARγ.

Background And Purpose: Inactivation of Cys (C674) in the sarcoplasmic/endoplasmic reticulum Ca ATPase 2 (SERCA2) causes intracellular Ca accumulation, which activates calcineurin-mediated nuclear factor of activated T-lymphocytes (NFAT)/NF-κB pathways, and results in the phenotypic modulation of smooth muscle cells (SMCs) to accelerate angiotensin II-induced aortic aneurysms. Our goal was to investigate the mechanism involved.

Experimental Approach: We used heterozygous SERCA2 C674S knock-in (SKI) mice, where half of C674 was substituted by serine, to mimic partial irreversible oxidation of C674.

Smooth muscle NADPH oxidase 4 promotes angiotensin II-induced aortic aneurysm and atherosclerosis by regulating osteopontin.

Background And Aims: Angiotensin II (Ang II) is commonly used to induce aortic aneurysm and atherosclerosis in animal models. Ang II upregulates NADPH oxidase isoform Nox4 in aortic smooth muscle cells (SMCs) in mice. However, whether smooth muscle Nox4 is directly involved in Ang II-induced aortic aneurysm and atherosclerosis is unclear.

Inactivation of cysteine 674 in the SERCA2 accelerates experimental aortic aneurysm.

Sarcoplasmic/endoplasmic reticulum Ca ATPase 2 (SERCA2) is vital to maintain intracellular calcium homeostasis. SERCA2 cysteine 674 (C674) is highly conservative and its irreversible oxidation is upregulated in human and mouse aortic aneurysms, especially in smooth muscle cells (SMCs). The contribution of SERCA2 and its redox C674 in the development of aortic aneurysm remains enigmatic.

Inactivation of Cys in SERCA2 increases BP by inducing endoplasmic reticulum stress and soluble epoxide hydrolase.

Background And Purpose: The kidney is essential in regulating sodium homeostasis and BP. The irreversible oxidation of Cys (C674) in the sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) is increased in the renal cortex of hypertensive mice. Whether inactivation of C674 promotes hypertension is unclear.

Metabolomics Deciphered Metabolic Reprogramming Required for Biofilm Formation.

Biofilm formation plays a key role in many bacteria causing infections, which mostly accounts for high-frequency infectious recurrence and antibiotics resistance. In this study, we sought to compare modified metabolism of biofilm and planktonic populations with UTI89, a predominant agent of urinary tract infection, by combining mass spectrometry based untargeted and targeted metabolomics methods, as well as cytological visualization, which enable us to identify the driven metabolites and associated metabolic pathways underlying biofilm formation. Surprisingly, our finding revealed distinct differences in both phenotypic morphology and metabolism between two patterns.

Mass spectrometry-derived systems biology technologies delineate the system's biochemical applications of siderophores.

Siderophores are chemically diverse secondary metabolites that primarily assist the host organisms to chelate iron. Siderophores are biosynthesized by many biological organisms, including bacteria, fungi, and plants and they are responsible for a variety of biological functions beyond capture iron. Thus, they could provide a novel understanding of host-pathogen interactions, plant physiology, disease pathogenesis, and drug development.

Brassinosteriod Insensitive 2 (BIN2) acts as a downstream effector of the Target of Rapamycin (TOR) signaling pathway to regulate photoautotrophic growth in Arabidopsis.

The components of the target of rapamycin (TOR) signaling pathway have been well characterized in heterotrophic organisms from yeast to humans. However, because of rapamycin insensitivity, embryonic lethality in tor null mutants and a lack of reliable ways of detecting TOR protein kinase in higher plants, the key players upstream and downstream of TOR remain largely unknown in plants. Using engineered rapamycin-sensitive Binding Protein 12-2 (BP12-2) plants, the present study showed that combined treatment with rapamycin and active-site TOR inhibitors (asTORis) results in synergistic inhibition of TOR activity and plant growth in Arabidopsis.

Bioinformatics facilitating the use of microarrays to delineate potential miRNA biomarkers in aristolochic acid nephropathy.

Aristolochic acid nephropathy (AAN) is a rapidly progressive acute or chronic tubulointerstitial nephritis (TIN). The present study attempted to explore the molecular mechanisms underlying the miRNA-directed development of AAN. Our differentially expressed analysis identified 11 DE-miRNAs and retrieved the target genes of these DE-miRNAs; then, network analysis and functional analysis further identified 6 DE-miRNAs (has-miR-192, has-miR-194, has-miR-542-3p, has-miR-450a, has-miR-584, has-miR-33a) as phenotypic biomarkers of AAN.

Expression profiling and functional analysis reveals that TOR is a key player in regulating photosynthesis and phytohormone signaling pathways in Arabidopsis.

Target of rapamycin (TOR) acts as a master regulator to control cell growth by integrating nutrient, energy, and growth factors in all eukaryotic species. TOR plays an evolutionarily conserved role in regulating the transcription of genes associated with anabolic and catabolic processes in Arabidopsis, but little is known about the functions of TOR in photosynthesis and phytohormone signaling, which are unique features of plants. In this study, AZD8055 (AZD) was screened as the strongest active-site TOR inhibitor (asTORi) in Arabidopsis compared with TORIN1 and KU63794 (KU).