Acceleration of Zeolite Crystallization: Current Status, Mechanisms, and Perspectives.

Zeolites are important classes of crystalline materials and possess well-defined channels and cages with molecular dimensions. They have been extensively employed as heterogeneous catalysts and gas adsorbents due to their relatively large specific surface areas, high pore volumes, compositional flexibility, definite acidity, and hydrothermal stability. The zeolite synthesis normally undergoes high-temperature hydrothermal treatments with a relatively long crystallization time, which exhibits low synthesis efficiency and high energy consumption. Various strategies, e.g., modulation of the synthesis gel compositions, employment of special silica/aluminum sources, addition of seeds, fluoride, hydroxyl (·OH) free radical initiators, and organic additives, regulation of the crystallization conditions, development of new approaches, etc., have been developed to overcome these obstacles. And, these achievements make prominent contributions to the topic of acceleration of the zeolite crystallization and promote the fundamental understanding of the zeolite formation mechanism. However, there is a lack of the comprehensive summary and analysis on them. Herein, we provide an overview of the recent achievements, highlight the significant progress in the past decades on the developments of novel and remarkable strategies to accelerate the crystallization of zeolites, and basically divide them into three main types, i.e., chemical methods, physical methods, and the derived new approaches. The principles/acceleration mechanisms, effectiveness, versatility, and degree of reality for the corresponding approaches are thoroughly discussed and summarized. Finally, the rational design of the prospective strategies for the fast synthesis of zeolites is commented on and envisioned. The information gathered here is expected to provide solid guidance for developing a more effective route to improve the zeolite crystallization and obtain the functional zeolite-based materials with more shortened durations and lowered cost and further promote their applications.

The cGAS-STING pathway: a therapeutic target in diabetes and its complications.

Diabetic wound healing (DWH) represents a major complication of diabetes where inflammation is a key impediment to proper healing. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has emerged as a central mediator of inflammatory responses to cell stress and damage. However, the contribution of cGAS-STING activation to impaired healing in DWH remains understudied. In this review, we examine the evidence that cGAS-STING-driven inflammation is a critical factor underlying defective DWH. We summarize studies revealing upregulation of the cGAS-STING pathway in diabetic wounds and discuss how this exacerbates inflammation and senescence and disrupts cellular metabolism to block healing. Partial pharmaceutical inhibition of cGAS-STING has shown promise in damping inflammation and improving DWH in preclinical models. We highlight key knowledge gaps regarding cGAS-STING in DWH, including its relationships with endoplasmic reticulum stress and metal-ion signaling. Elucidating these mechanisms may unveil new therapeutic targets within the cGAS-STING pathway to improve healing outcomes in DWH. This review synthesizes current understanding of how cGAS-STING activation contributes to DWH pathology and proposes future research directions to exploit modulation of this pathway for therapeutic benefit.

Targeting DNA methylation and demethylation in diabetic foot ulcers.

BACKGROUND: Poor wound healing is a significant complication of diabetes, which is commonly caused by neuropathy, trauma, deformities, plantar hypertension and peripheral arterial disease. Diabetic foot ulcers (DFU) are difficult to heal, which makes patients susceptible to infections and can ultimately conduce to limb amputation or even death in severe cases. An increasing number of studies have found that epigenetic alterations are strongly associated with poor wound healing in diabetes. AIM OF REVIEW: This work provides significant insights into the development of therapeutics for improving chronic diabetic wound healing, particularly by targeting and regulating DNA methylation and demethylation in DFU. Key scientific concepts of review: DNA methylation and demethylation play an important part in diabetic wound healing, via regulating corresponding signaling pathways in different breeds of cells, including macrophages, vascular endothelial cells and keratinocytes. In this review, we describe the four main phases of wound healing and their abnormality in diabetic patients. Furthermore, we provided an in-depth summary and discussion on how DNA methylation and demethylation regulate diabetic wound healing in different types of cells; and gave a brief summary on recent advances in applying cellular reprogramming techniques for improving diabetic wound healing.

Protective effect of solanesol in glucose-induced hepatocyte injury: Mechanistic insights on oxidative stress and mitochondrial preservation.

Solanesol is a tetra sesquiterpene enol with various biological activities. Modern medical studies have confirmed that solanesol has the function of lipid antioxidation and scavenges free radicals. This study aimed to investigate the protective effect of solanesol against oxidative damage induced by high glucose on human normal hepatocytes (L-02 cells) and its possible mechanism. The results showed that solanesol could effectively improve the decrease of cell viability induced by high glucose, decrease the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in the extracellular medium, increased the enzyme activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), balanced the level of reactive oxygen species (ROS) in cells, inhibited lipid peroxidation of all kinds of biological membranes, and restored mitochondrial membrane potential (MMP). In addition, Solanesol also inhibited the expression of Keap1, promoted the nuclear translocation of Nrf2 by hydrogen bonding with Nrf2, and activated the expression of downstream antioxidant factors NQO1 and HO-1. Altogether, these findings suggest that solanesol may be a potential protectant against diabetic liver injury.

Preparation and Safety Evaluation of Centella asiatica Total Glycosides Nitric Oxide Gel and Its Therapeutic Effect on Diabetic Cutaneous Ulcers.

Diabetic cutaneous ulcers (DCU) are a chronic and refractory complication of diabetes mellitus, which can lead to amputation or even death in extreme cases. Promoting the early healing of DCU and reducing the disability rate and treatment cost are important research topics in treating with integrated traditional Chinese and Western medicine. Centella asiatica total glycosides are extracted from the traditional Chinese medicine Centella asiatica and have angiogenic, anticancer, antioxidant, and wound healing effects. Nitric oxide (NO) is a critical component of wound healing. During the development of DCU, endogenous NO secretion is insufficient. It has been reported that exogenous nitric oxide can promote wound healing, but it is difficult to adhere to the skin because of its short half-life. Therefore, in this study, we used the polymer excipient hydroxyethyl cellulose as the matrix, combined with Centella asiatica total glycosides and NO, and developed a new type of topical gel that can promote wound healing. At the same time, we made a comprehensive research and evaluation on the preparation technology, quality standard, skin toxicity, reproductive toxicity, and pharmacodynamics against diabetic skin ulcers of the gel. According to our research results, the combination of Centella asiatica total glycosides and nitric oxide can accelerate the healing speed of DCU wounds, and 8% Centella asiatica total glycosides nitric oxide gel (CATGNOG) has the best effect in ulcer wound healing. CATGNOG has the advantages of feasible preparation method, controllable quality, good stability at low temperature, and no apparent skin toxicity and reproductive toxicity. It can effectively inhibit the growth of bacteria on the wound surface, relieve the inflammatory reaction of the wound surface, and promote the healing of ulcer wound, which provides a basis for further research of the preparation in the future.

Fibroblasts: Immunomodulatory factors in refractory diabetic wound healing.

Diabetes is a systemic disease in which patients with diabetes may develop peripheral neuropathy of the lower extremities and peripheral vascular disease due to long-term continuous exposure to high glucose. Delayed wound healing in diabetes is one of the major complications of diabetes. Slow wound healing in diabetic patients is associated with high glucose toxicity. When the condition deteriorates, the patient needs to be amputated, which seriously affects the quality of life and even endangers the life of the patient. In general, the delayed healing of diabetes wound is due to the lack of chemokines, abnormal inflammatory response, lack of angiogenesis and epithelial formation, and fibroblast dysfunction. The incidence of several chronic debilitating conditions is increasing in patients with diabetes, such as chronic renal insufficiency, heart failure, and hepatic insufficiency. Fibrosis is an inappropriate deposition of extracellular matrix (ECM) proteins. It is common in diabetic patients causing organ dysfunction. The fibrotic mechanism of diabetic fibroblasts may involve direct activation of permanent fibroblasts. It may also involve the degeneration of fibers after hyperglycemia stimulates immune cells, vascular cells, or organ-specific parenchymal cells. Numerous studies confirm that fibroblasts play an essential role in treating diabetes and its complications. The primary function of fibroblasts in wound healing is to construct and reshape the ECM. Nowadays, with the widespread use of single-cell RNA sequencing (scRNA-seq), an increasing number of studies have found that fibroblasts have become the critical immune sentinel cells, which can detect not only the activation and regulation of immune response but also the molecular pattern related to the injury. By exploring the heterogeneity and functional changes of fibroblasts in diabetes, the manuscript discusses that fibroblasts may be used as immunomodulatory factors in refractory diabetic wound healing, providing new ideas for the treatment of refractory diabetic wound healing.

Molecular mechanisms of Marine-Derived Natural Compounds as photoprotective strategies.

Excessive exposure of the skin to ultraviolet radiation (UVR) causes oxidative stress, inflammation, immunosuppression, apoptosis, and changes in the extracellular matrix, which lead to the development of photoaging and photodamage of skin. At the molecular level, these pathological changes are mainly caused by the activation of related protein kinases and downstream transcription pathways, the increase of matrix metalloproteinase, the formation of reactive oxygen species, and the combined action of cytokines and inflammatory mediators. At present, the photostability, toxicity, and damage to marine ecosystems of most sun protection products in the market have affected their efficacy and safety. Another way is to use natural products produced by various marine species. Marine organisms have evolved a variety of molecular strategies to protect themselves from the harmful effects of ultraviolet radiation, and their unique chemicals have attracted more and more attention in the research of photoprotection and photoaging resistance. This article provides an extensive description of the recent literature on the potential of Marine-Derived Natural Compounds (MDNCs) as photoprotective and photoprotective agents. It reviews the positive effects of MDNCs in counteracting UV-induced oxidative stress, inflammation, DNA damage, apoptosis, immunosuppression, and extracellular matrix degradation. Some MDNCs have the potential to develop feasible solutions for related phenomena, such as photoaging and photodamage caused by UVR.

Dendrobium nobile Lindl. Polysaccharides protect fibroblasts against UVA-induced photoaging via JNK/c-Jun/MMPs pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium nobile Lindl. is an orchid species that is found throughout Asia, including Thailand, Laos, Vietnam, and China. It has been used to treat tumors, hyperglycemia, hyperlipidemia, and neurological disorders caused by aging in recent decades. AIM OF THE STUDY: To investigate the antagonistic effect of Dendrobium nobile Lindl. Polysaccharides (DNLP) on UVA-induced photoaging of Human foreskin fibroblasts (HFF-1) and explore its possible anti-aging mechanisms. MATERIALS AND METHODS: An in vitro photoaging model of dermal fibroblasts was established with multiple UVA irradiations. Fibroblasts were treated with 0.06 mg/ml, 0.18 mg/ml, 0.54 mg/ml of DNLP one day before photodamage induction. The levels of reactive oxygen species (ROS), Malondialdehyde (MDA), cell viability and longevity, Superoxide Dismutase (SOD), Catalase (CAT), and Glutathione peroxidase (GSH-Px) enzymatic activities were determined. We examined how DNLP ameliorates the effects of photoaging, the JNK/c-Fos/c-Jun pathway, senescence-associated ß-galactosidase (SA-ß-Gal), and MMP expression levels were measured. RESULTS: UVA irradiation reduced the viability, lifespan, and proliferation of HFF-1 cells, increased ROS and lipid peroxidation and decreased the activities of free radical scavenging enzyme systems SOD, CAT, and GSH-Px. DNLP treatment can reverse UVA damage, reduce SA-ß-Gal expression, reduce phosphorylation activation of the JNK/c-Fos/c-Jun pathway and inhibit MMP-1, MMP-2 MMP-3, and MMP-9 protein expression. CONCLUSIONS: DNLP can effectively inhibit UVA damage to HFF-1 and prevent cell senescence. Its mechanism of action may increase antioxidant enzyme activity while inhibiting JNK pathway activation and MMPs expression.

Macrophage polarization in diabetic wound healing.

Impaired wound healing is one of the severe complications of diabetes. Macrophages have been shown to play a vital role in wound healing. In different wound environments, macrophages are classified into two phenotypes: classically activated macrophages and alternatively activated macrophages. Dysregulation of macrophage phenotypes leads to severely impaired wound healing in diabetes. Particularly, uncontrolled inflammation and abnormal macrophage phenotype are important reasons hindering the closure of diabetic wounds. This article reviews the functions of macrophages at various stages of wound healing, the relationship between macrophage phenotypic dysregulation and diabetic wound healing and the mechanism of macrophage polarization in diabetic wound healing. New therapeutic drugs targeting phagocyte polarization to promote the healing of diabetic wounds might provide a new strategy for treating chronic diabetic wound healing.

Fibroblast Growth Factor in Diabetic Foot Ulcer: Progress and Therapeutic Prospects.

Diabetic foot ulcer (DFU) is a combination of neuropathy and various degrees of peripheral vasculopathy in diabetic patients resulting in lower extremity infection, ulcer formation, and deep-tissue necrosis. The difficulty of wound healing in diabetic patients is caused by a high glucose environment and various biological factors in the patient. The patients' skin local microenvironment changes and immune chemotactic response dysfunction. Wounds are easy to be damaged and ulcerated repeatedly, but difficult to heal, and eventually develop into chronic ulcers. DFU is a complex biological process in which many cells interact with each other. A variety of growth factors released from wounds are necessary for coordination and promotion of healing. Fibroblast growth factor (FGF) is a family of cell signaling proteins, which can mediate various processes such as angiogenesis, wound healing, metabolic regulation and embryonic development through its specific receptors. FGF can stimulate angiogenesis and proliferation of fibroblasts, and it is a powerful angiogenesis factor. Twenty-three subtypes have been identified and divided into seven subfamilies. Traditional treatments for DFU can only remove necrotic tissue, delay disease progression, and have a limited ability to repair wounds. In recent years, with the increasing understanding of the function of FGF, more and more researchers have been applying FGF-1, FGF-2, FGF-4, FGF-7, FGF-21 and FGF-23 topically to DFU with good therapeutic effects. This review elaborates on the recently developed FGF family members, outlining their mechanisms of action, and describing their potential therapeutics in DFU.

The Multiple Roles of Fibroblast Growth Factor in Diabetic Nephropathy.

Diabetic nephropathy (DN) is a common microvascular complication in the late stages of diabetes. Currently, the etiology and pathogenesis of DN are not well understood. Even so, available evidence shows its development is associated with metabolism, oxidative stress, cytokine interaction, genetic factors, and renal microvascular disease. Diabetic nephropathy can lead to proteinuria, edema and hypertension, among other complications. In severe cases, it can cause life-threatening complications such as renal failure. Patients with type 1 diabetes, hypertension, high protein intake, and smokers have a higher risk of developing DN. Fibroblast growth factor (FGF) regulates several human processes essential for normal development. Even though FGF has been implicated in the pathological development of DN, the underlying mechanisms are not well understood. This review summarizes the role of FGF in the development of DN. Moreover, the association of FGF with metabolism, inflammation, oxidative stress and fibrosis in the context of DN is discussed. Findings of this review are expected to deepen our understanding of DN and generate ideas for developing effective prevention and treatments for the disease.

FGF, Mechanism of Action, Role in Parkinson's Disease, and Therapeutics.

Parkinson's disease (PD) is a neurodegenerative disease associated with severe disability and adverse effects on life quality. In PD, motor dysfunction can occur, such as quiescence, muscle stiffness, and postural instability. PD is also associated with autonomic nervous dysfunction, sleep disorders, psychiatric symptoms, and other non-motor symptoms. Degeneration of dopaminergic neurons in the substantia nigra compact (SNPC), Lewy body, and neuroinflammation are the main pathological features of PD. The death or dysfunction of dopaminergic neurons in the dense part of the substantia nigra leads to dopamine deficiency in the basal ganglia and motor dysfunction. The formation of the Lewy body is associated with the misfolding of α-synuclein, which becomes insoluble and abnormally aggregated. Astrocytes and microglia mainly cause neuroinflammation, and the activation of a variety of pro-inflammatory transcription factors and regulatory proteins leads to the degeneration of dopaminergic neurons. At present, PD is mainly treated with drugs that increase dopamine concentration or directly stimulate dopamine receptors. Fibroblast growth factor (FGF) is a family of cellular signaling proteins strongly associated with neurodegenerative diseases such as PD. FGF and its receptor (FGFR) play an essential role in the development and maintenance of the nervous system as well as in neuroinflammation and have been shown to improve the survival rate of dopaminergic neurons. This paper summarized the mechanism of FGF and its receptors in the pathological process of PD and related signaling pathways, involving the development and protection of dopaminergic neurons in SNPC, α-synuclein aggregation, mitochondrial dysfunction, and neuroinflammation. It provides a reference for developing drugs to slow down or prevent the potential of PD.