Silk Sericin and Its Composite Materials with Antibacterial Properties to Enhance Wound Healing: A Review.

Wound infections may disrupt the normal wound-healing process. Large amounts of antibiotics are frequently used to prevent pathogenic infections; however, this can lead to resistance development. Biomaterials possessing antimicrobial properties have promising applications for reducing antibiotic usage and promoting wound healing. Silk sericin (SS) has been increasingly explored for skin wound healing applications owing to its excellent biocompatibility and antioxidant, antimicrobial, and ultraviolet-resistant properties. In recent years, SS-based composite biomaterials with a broader antimicrobial spectrum have been extensively investigated and demonstrated favorable efficacy in promoting wound healing. This review summarizes various antimicrobial agents, including metal nanoparticles, natural extracts, and antibiotics, that have been incorporated into SS composites for wound healing and elucidates their mechanisms of action. It has been revealed that SS-based biomaterials can achieve sustained antimicrobial activity by slow-release-loaded antimicrobial agents. The antimicrobial-loaded SS composites may promote wound healing through anti-infection, anti-inflammation, hemostasis, angiogenesis, and collagen deposition. The manufacturing methods, benefits, and limitations of antimicrobial-loaded SS materials are briefly discussed. This review aims to enhance the understanding of new advances and directions in SS-based antimicrobial composites and guide future biomedical research.

Sericin promotes chondrogenic proliferation and differentiation via glycolysis and Smad2/3 TGF-ß signaling inductions and alleviates inflammation in three-dimensional models.

Knee osteoarthritis is a chronic joint disease mainly characterized by cartilage degeneration. The treatment is challenging due to the lack of blood vessels and nerve supplies in cartilaginous tissue, causing a prominent limitation of regenerative capacity. Hence, we investigated the cellular promotional and anti-inflammatory effects of sericin, Bombyx mori-derived protein, on three-dimensional chondrogenic ATDC5 cell models. The results revealed that a high concentration of sericin promoted chondrogenic proliferation and differentiation and enhanced matrix production through the increment of glycosaminoglycans, COL2A1, COL X, and ALP expressions. SOX-9 and COL2A1 gene expressions were notably elevated in sericin treatment. The proteomic analysis demonstrated the upregulation of phosphoglycerate mutase 1 and triosephosphate isomerase, a glycolytic enzyme member, reflecting the proliferative enhancement of sericin. The differentiation capacity of sericin was indicated by the increased expressions of procollagen12a1, collagen10a1, rab1A, periostin, galectin-1, and collagen6a3 proteins. Sericin influenced the differentiation capacity via the TGF-ß signaling pathway by upregulating Smad2 and Smad3 while downregulating Smad1, BMP2, and BMP4. Importantly, sericin exhibited an anti-inflammatory effect by reducing IL-1ß, TNF-α, and MMP-1 expressions and accelerating COL2A1 production in the early inflammatory stage. In conclusion, sericin demonstrates potential in promoting chondrogenic proliferation and differentiation, enhancing cartilaginous matrix synthesis through glycolysis and TGF-ß signaling pathways, and exhibiting anti-inflammatory properties.

Porous gradient hydrogel promotes skin regeneration by angiogenesis.

The skin has a multilayered structure, and deep-seated injuries are exposed to external microbial invasion and in vivo microenvironmental destabilization. Here, a bilayer bionic skin scaffold (Bilayer SF) was developed based on methacrylated sericin protein to mimic the skin's multilayered structure and corresponding functions. The outer layer (SF@TA), which mimics the epidermal layer, was endowed with the function of resisting external bacterial and microbial invasion using a small pore structure and bio-crosslinking with tannic acid (TA). The inner layer (SF@DA@Gel), which mimics the dermal layer, was used to promote cellular growth using a large pore structure and introducing dopamine (DA) to regulate the wound microenvironment. This Bilayer SF showed good mechanical properties and structural stability, satisfactory antioxidant and promote cell proliferation and migration abilities. In vitro studies confirmed the antimicrobial properties of the outer layer and the pro-angiogenic ability of the inner layer. In vivo animal studies demonstrated that the bilayer scaffolds promoted collagen deposition, neovascularization, and marginal hair follicle formation, which might be a promising new bionic skin scaffold.

Oral sericin ameliorates type 2 diabetes through passive intestinal and bypass transport into the systemic circulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Boiled silkworm cocoons have been used to treat 'Xiaoke disease' (diabetes mellitus) recorded in Chinese medicine for over 800 years. In recent years, it has been found that the active substance silk sericin (SS) has therapeutic benefits in treating type 2 diabetes mellitus (T2DM). SS promotes pancreatic islet signalling, the proliferation of pancreatic islet cells, and insulin secretion. It is inferred that SS enters the bloodstream after oral administration and plays a role in the body's circulation. As a natural protein, SS needs to resist digestion by proteases in the gastrointestinal tract and cross the gastrointestinal barrier after oral administration. It is currently unclear how SS crosses the gastrointestinal barrier and whether it exerts therapeutic effects on T2DM by entering the circulation. AIM OF THE STUDY: To study how SS crosses the gastrointestinal barrier and whether it enters the body circulation to exert a therapeutic effect on T2DM. MATERIALS AND METHODS: SS was extracted from silkworm cocoons using an alkaline method with sodium carbonate. The antidigestive capacity of SS was detected using SDS-PAGE gel electrophoresis experiments. The mode of uptake and translocation of orally consumed SS in vivo was analysed using the AP-side to BL-side and BL-side-AP-side translocations, apparent Permeability coefficient (Papp), and Exocytosis rates (ER). The study compared the differences between the adSS group and the adSS + EDTA group by using Ethylenediaminetetraacetic acid (EDTA) to separate the tight junctions between Caco-2 cells. The aim was to analyze whether the transport mode of oral filaggrin proteins in vivo could be absorbed by bypass transport. By administering SS through oral and intraperitoneal injection to type 2 diabetic mice, we measured its concentration in the blood, as well as blood glucose and insulin levels, to determine its effectiveness in treating diabetes and its ability to enter the body's circulation for treatment. RESULTS: The molecular weight of SS decreased from 10k∼25 kDa to 10k∼15 kDa after in vitro simulated gastrointestinal fluid digestion, indicating its good antidigestive properties. The apparent Papp was greater than 1 × 10-6 cm·s-1, and the ER was between 0.5 and 1.5, indicating that adSS was well-absorbed and mainly passively transported. The Caco-2 cell model showed that the addition of EDTA promoted the transport of adSS, resulting in significantly larger Papp and ER values, indicating that adSS was absorbed by bypass transport. After oral administration of SS, the concentration of SS in the blood was lower than after intraperitoneal injection, which is 60% of intraperitoneal administration. Mice with a T2DM model who were administered SS for 5 weeks showed significant improvement in insulin resistance and glucose tolerance. Additionally, the pancreatic tissue appeared more regular. In the treatment of T2DM, injections of SS have been shown to be more effective than oral administration. Both oral and intraperitoneal injections have been partially involved in the circulation. CONCLUSIONS: SS is enzymatically cleaved by proteolytic enzymes in the gastrointestinal tract. The smaller molecules are partially absorbed into the body's circulation through passive and paracrine transport, exerting a therapeutic effect on T2DM.

Melatonin/Sericin Wound Healing Patches: Implications for Melanoma Therapy.

Melatonin and sericin exhibit antioxidant properties and may be useful in topical wound healing patches by maintaining redox balance, cell integrity, and regulating the inflammatory response. In human skin, melatonin suppresses damage caused by ultraviolet radiation (UVR) which involves numerous mechanisms associated with reactive oxygen species/reactive nitrogen species (ROS/RNS) generation and enhancing apoptosis. Sericin is a protein mainly composed of glycine, serine, aspartic acid, and threonine amino acids removed from the silkworm cocoon (particularly Bombyx mori and other species). It is of interest because of its biodegradability, anti-oxidative, and anti-bacterial properties. Sericin inhibits tyrosinase activity and promotes cell proliferation that can be supportive and useful in melanoma treatment. In recent years, wound healing patches containing sericin and melatonin individually have attracted significant attention by the scientific community. In this review, we summarize the state of innovation of such patches during 2021-2023. To date, melatonin/sericin-polymer patches for application in post-operational wound healing treatment has been only sparingly investigated and it is an imperative to consider these materials as a promising approach targeting for skin tissue engineering or regenerative dermatology.

The impact of sericin on inflammation, oxidative stress, and lipid metabolism in female rats with experimental knee osteoarthritis.

OBJECTIVE: This study investigated the effects of sericin on inflammation, oxidative stress, and lipid metabolism in female rats with experimental knee osteoarthritis (KOA), focusing on evaluating its effectiveness via the sterol regulatory protein (SREBP)-1C and SREBP-2 pathways. METHODS: The rats were randomly assigned to three experimental groups: the C group (control), the KOA group (KOA control), and the sericin group (KOA + sericin). The KOA model was created by injecting monosodium iodoacetate (MIA) into the knee joint. Sericin was administered intra-articularly to rats on days 1, 7, 14, and 21 (0.8 g/kg/mL, 50 µL). After 21 days, the rats were sacrificed, and serum samples were analyzed using an ELISA to measure tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), IL-10, SREBP-1c, SREBP-2, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), cholesterol, triglyceride, and total oxidant-antioxidant status (TOS-TAS) levels. RESULTS: The KOA group exhibited higher serum TNF-α, IL-1ß, TOS, SREBP-1C, ACC, FAS, triglyceride, SREBP-2, and cholesterol levels than the C group (P < 0.05). However, the levels of these cytokines, except cholesterol, were significantly lower in the sericin group than in the KOA group. The KOA group exhibited significantly lower serum TAS and IL-10 levels than the C group (P < 0.05). In the sericin group, there was a statistically significant increase (P < 0.05). CONCLUSION: Sericin shows promising potential for reducing inflammation, oxidative stress, and lipid metabolism in experimental models of KOA in rats. However, further clinical research is necessary to validate the potential of sericin as a therapeutic agent for treating KOA. Key Points • Sericin can reduce knee osteoarthritis (KOA) symptoms in an experimental rat model. • In particular, in the serum of an experimental KOA rat model, sericin specifically reduces the levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1ß), and increases the levels of anti-inflammatory cytokines, such as IL-10. • Sericin reduced lipid metabolism via the sterol regulatory protein (SREBP)-1C and SREBP-2 pathways and oxidative stress in the serum of the experimental KOA rat model. • The intra-articular administration of sericin has been shown to significantly reduce lipid metabolism, oxidative stress, and inflammation, as supported by biochemical analysis. These findings suggest its promising potential as an alternative treatment option for KOA.

Thymosin beta 10 loaded ZIF-8/sericin hydrogel promoting angiogenesis and osteogenesis for bone regeneration.

Angiogenesis is pivotal for osteogenesis during bone regeneration. A hydrogel that promotes both angiogenesis and osteogenesis is essential in bone tissue engineering. However, creating scaffolds with the ideal balance of biodegradability, osteogenic, and angiogenic properties poses a challenge. Thymosin beta 10 (TMSB10), known for its dual role in angiogenesis and osteogenesis differentiation, faces limitations due to protein activity preservation. To tackle this issue, ZIF-8 was engineered as a carrier for TMSB10 (TMSB10@ZIF-8), and subsequently integrated into the self-assembled sericin hydrogel. The efficacy of the composite hydrogel in bone repair was assessed using a rat cranial defect model. Characterization of the nanocomposites confirmed the successful synthesis of TMSB10@ZIF-8, with a TMSB10 encapsulation efficiency of 88.21 %. The sustained release of TMSB10 from TMSB10@ZIF-8 has significantly enhanced tube formation in human umbilical vein endothelial cells (HUVECs) in vitro and promoted angiogenesis in the chicken chorioallantoic membrane (CAM) model in vivo. It has markedly improved the osteogenic differentiation ability of MC 3 T3-E1 cells in vitro. 8 weeks post-implantation, the TMSB10@ZIF-8/ Sericin hydrogel group exhibited significant bone healing (86.77 ± 8.91 %), outperforming controls. Thus, the TMSB10@ZIF-8/Sericin hydrogel, leveraging ZIF-8 for TMSB10 delivery, emerges as a promising bone regeneration scaffold with substantial clinical application potential.

[A sericin hydrogel scaffold for sustained dexamethasone release modulates macrophage polarization to promote mandibular bone defect repair in rats].

OBJECTIVE: To evaluate the efficacy of a modified sericin hydrogel scaffold loaded with dexamethasone (SMH-CD/DEX) scaffold for promoting bone defect healing by stimulating anti-inflammatory macrophage polarization. METHODS: The light-curable SMH-CD/DEX scaffold was prepared using dexamethasone-loaded NH2-ß-cyclodextrin (NH2-ß-CD) and sericin hydrogel and characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), biocompatibility assessment and drug release test. THP-1 macrophages incubated with the scaffold were examined for protein expressions of iNOS and Arg-1, mRNA expressions of IL-6, Il-10, Arg-1 and iNOS, and surface markers CD86 and CD206 using Western blotting, RT-qPCR, and flow cytometry. In a co-culture system of human periodontal ligament stem cells (HPDLSCs) and THP-1 macrophages, the osteogenic ability of the stem cells incubated with the scaffold was evaluated by detecting protein expressions of COL1A1 and Runx2 and expressions of ALP, Runx2, OCN and BMP2 mRNA, ALP staining, and alizarin red staining. In a rat model of mandibular bone defect, the osteogenic effect of the scaffold was assessed by observing bone regeneration using micro-CT and histopathological staining. RESULTS: In THP-1 macrophages, incubation with SMH-CD/DEX scaffold significantly enhanced protein expressions of Arg-1 and mRNA expressions of IL-10 and Arg-1 and lowered iNOS protein expression and IL-6 and iNOS mRNA expressions. In the co-culture system, SMH-CD/DEX effectively increased the protein expressions of COL1A1 and Runx2 and mRNA expressions of ALP and BMP2 in HPDLSCs and promoted their osteogenic differentiation. In the rat models, implantation of SMH-CD/DEX scaffold significantly promoted bone repair and bone regeneration in the bone defect. CONCLUSION: The SMH-CD/DEX scaffold capable of sustained dexamethasone release promotes osteogenic differentiation of stem cells and bone defect repair in rats by regulating M2 polarization.

The Potential of Natural Carotenoids-Containing Sericin of the Domestic Silkworm Bombyx mori.

Sericin derived from the white cocoon of Bombyx mori has been attracting more attention for its utilization in food, cosmetics, and biomedicine. The potential health benefits of natural carotenoids for humans have also been well-established. Some rare strains of Bombyx mori (B. mori) produce yellow-red cocoons, which endow a potential of natural carotenoid-containing sericin. We hypothesized that natural carotenoid-containing sericin from yellow-red cocoons would exhibit better properties compared with white cocoon sericin. To investigate the physicochemical attributes of natural carotenoid-containing sericin, we bred two silkworm strains from one common ancestor, namely XS7 and XS8, which exhibited different cocoon colors as a result of the inconsistent distribution of lutein and ß-carotene. Compared with white cocoon sericin, the interaction between carotenoids and sericin molecules in carotenoid-containing sericin resulted in a unique fluorescence emission at 530, 564 nm. The incorporation of carotenoids enhanced the antibacterial effect, anti-cancer ability, cytocompatibility, and antioxidant of sericin, suggesting potential wide-ranging applications of natural carotenoid-containing sericin as a biomass material. We also found differences in fluorescence characteristics, antimicrobial effects, anti-cancer ability, and antioxidants between XS7 and XS8 sericin. Our work for the first time suggested a better application potential of natural carotenoid-containing sericin as a biomass material than frequently used white cocoon sericin.

Transcriptomic screening of novel targets of sericin in human hepatocellular carcinoma cells.

Sericin, a natural protein derived from Bombyx mori, is known to ameliorate liver tissue damage; however, its molecular mechanism remains unclear. Herein, we aimed to identify the possible novel targets of sericin in hepatocytes and related cellular pathways. RNA sequencing analysis indicated that a low dose of sericin resulted in 18 differentially expressed genes (DEGs) being upregulated and 68 DEGs being downregulated, while 61 DEGs were upregulated and 265 DEGs were downregulated in response to a high dose of sericin (FDR ≤ 0.05, fold change > 1.50). Functional analysis revealed that a low dose of sericin regulated pathways associated with the complement and coagulation cascade, metallothionine, and histone demethylate (HDMs), whereas a high dose of sericin was associated with pathways involved in lipid metabolism, mitogen-activated protein kinase (MAPK) signaling and autophagy. The gene network analysis highlighted twelve genes, A2M, SERPINA5, MT2A, MT1G, MT1E, ARID5B, POU2F1, APOB, TRAF6, HSPA8, FGFR1, and OGT, as novel targets of sericin. Network analysis of transcription factor activity revealed that sericin affects NFE2L2, TFAP2C, STAT1, GATA3, CREB1 and CEBPA. Additionally, the protective effects of sericin depended on the counterregulation of APOB, POU2F1, OGT, TRAF6, and HSPA5. These findings suggest that sericin exerts hepatoprotective effects through diverse pathways at different doses, providing novel potential targets for the treatment of liver diseases.

Green cocoon-derived sericin reduces cellular damage caused by radiation in human keratinocytes.

Radiation therapy used in the treatment of cancer causes skin damage, and no method of care has been established thus far. Recently, it has become clear that sericin derived from silkworm cocoons has moisturizing and antioxidant functions. In addition, green cocoon-derived sericin, which is rich in flavonoids, may have enhanced functions. However, whether this green cocoon-derived sericin can reduce radiotherapy-induced skin damage is unclear. In the present study, we aimed at establishing care methods to reduce skin cell damage caused by X-irradiation using green cocoon-derived sericin. We investigated its effect on human keratinocytes using lactate dehydrogenase activity to indicate damage reduction. Our results showed that green cocoon-derived sericin reduced cell damage caused by X-irradiation. However, this effect was not observed when cells were treated before X-irradiation or with a sericin derived from white cocoons. In addition, green cocoon-derived sericin decreased the levels of reactive oxygen species and lipid peroxidation. Our results suggest that green cocoon sericin mitigates the damaging effect of X-irradiation on cells, hence presenting potential usefulness in reducing skin damage from radiation therapy and opening new avenues in the care of cancer patients.

Transparent injectable sericin-honey hydrogel with antioxidant and antibacterial activities combined with feeding sericin accelerates diabetic wound healing.

Wound healing in diabetics is often impaired or delayed due to the presence of high reactive oxygen species and low antioxidant levels. Here, a sericin-honey semi-interpenetrating network hydrogel with excellent antioxidant activity was prepared. Besides, the sericin-honey hydrogel is transparent, injectable, sticky, highly porous, and has good swelling properties, antibacterial activity, and cell compatibility. Based on its good performancein vitro, sericin-honey hydrogel achieved effectivein vivotreatment on a mouse diabetic wound model, significantly accelerating the wound healing process. Furthermore, the combined effect of feeding sericin solution played a positive role in strengthening the effect of diabetic wound repair.

Anti-inflammatory effects of sericin and swimming exercise in treating experimental Achilles tendinopathy in rat.

The aim of this study was to assess the effectiveness of combining sericin with swimming exercise as a treatment for type-I collagenase-induced Achilles tendinopathy (AT) in rats, with a focus on inflammatory cytokines. An experimental AT model was established using type-I collagenase in male Sprague-Dawley rats, categorized into five groups: Group 1 (Control + Saline), Group 2 (AT), Group 3 (AT + exercise), Group 4 (AT + sericin), and Group 5 (AT + sericin + exercise). Intratendinous sericin administration (0.8 g/kg/mL) took place from days 3 to 6, coupled with 30 min daily swimming exercise sessions (5 days/week, 4 weeks). Serum samples were analyzed using ELISA for tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-10 (IL-10), and total antioxidant-oxidant status (TAS-TOS), alongside histopathological and immunohistochemical assessments of Achilles tendon samples. Elevated TNF-α and IL-1ß and decreased IL-10 levels were evident in Group 2; Of these, TNF-α and IL-1ß were effectively reduced and IL-10 increased across all treatment groups, particularly groups 4 and 5. Serum TAS was notably lower in Group 2 and significantly increased in Group 5 compared to Group 2. Histopathologically, Group 2 displayed severe degeneration, irregular fibers, and round cell nuclei, while Group 5 exhibited decreased degeneration and spindle-shaped fibers. The Bonar score increased in Group 2 and decreased in groups 4 and 5. Collagen type-I alpha-1 (Col1A1) expression was notably lower in Group 2 (P = 0.001) and significantly increased in groups 4 and 5 compared to Group 2 (P = 0.011 and 0.028, respectively). This study underscores the potential of sericin and swimming exercises in mitigating inflammation and oxidative stress linked to AT pathogenesis, presenting a promising combined therapeutic strategy.

Antioxidant sericin averts the disruption of oocyte-follicular cell communication triggered by oxidative stress.

Antioxidants are free radical scavengers that increase oocyte quality and improve female fertility by suppressing oxidative stress. However, the related mechanisms remain unclear. The present study was designed to examine whether a reduction of oxidative stress from using the antioxidant sericin led to expanded cumulus cell (CC)-oocyte communication and oocyte developmental acquisition in a bovine model. We found that cumulus-oocyte complexes (COCs) matured in the presence of sericin showed a significantly increased oocyte meiotic maturation rate (P < 0.01) and accelerated subsequent blastocyst formation, as more blastocysts were found at the hatched stage (P < 0.05) compared to that in the control group. In contrast to the control group, sericin suppressed H2O2 levels in COCs, resulting in a markedly enhanced CC-oocyte gap junction communication index and number of transzonal projections, which were preserved until 18 h of oocyte maturation. These findings indicate that sericin reduces disruption of oocyte-follicular cell communication induced by oxidative stress. Sericin consistently increased intra-oocyte glutathione (GSH) levels and reduced oocyte H2O2 levels (P < 0.05), both of which were ablated when GSH synthesis was inhibited by buthionine sulfoximide (an inhibitor of GSH synthesis). Furthermore, the inhibition of GSH synthesis counteracted the positive effects of sericin on subsequent embryo developmental competence (P < 0.01). Intra-oocyte GSH levels were positively associated with blastocyst development and quality. These outcomes demonstrate new perspectives for the improvement of oocyte quality in assisted reproductive technology and may contribute to developing treatment strategies for infertility and cancer.

In vitro and in vivo anti-colorectal cancer effect of the newly synthesized sericin/propolis/fluorouracil nanoplatform through modulation of PI3K/AKT/mTOR pathway.

The present work aimed to assess the potential effect of sericin/propolis/fluorouracil nanoformula against colorectal cancer (CRC) (the fourth most common cause of cancer-related mortalities). A novel anti-cancerous formula of the synthesized sericin/propolis nanoparticles was developed and tested both in vitro (using Caco-2 cell line) and in vivo (in experimentally induced colorectal cancer animal models). The combination index of the prepared nanoformula proved that the combination between sericin/propolis nanoparticles and 5-fluorouracil demonstrated the highest synergistic effect (0.86), with dose reduction index (DRI) of the chemotherapeutic drug reaching 1.49. The mechanism of action of the prepared nanoformula revealed that it acts through the inhibition of the PI3K/AKT/mTOR signaling pathway and consequently inhibiting cancerous cells proliferation. Treatment and prophylactic studies of both sericin and propolis showed increased TBARS (Thiobarbituric Acid Reactive Substance) formation, downregulated BCL2 (B-cell lymphoma 2) and activated BAX, Caspase 9 and Caspase 3 expression. The prepared nanoformula decreased the ROS (Reactive Oxygen Species) production in vivo owing to PI3K/AKT/mTOR pathway inhibition and FOXO-1 (Forkhead Box O1) activation that resulted in autophagy/apoptosis processes stimulation. The potent anticancer effect of the prepared nanoformula was further emphasized through the in vivo histopathological studies of experimentally induced tumors. The newly formulated sericin/propolis/fluorouracil nanoparticles exhibited clear-cut cytotoxic effects toward tumor cells with provided evidence for the prophylactic effect.

Sericin and melatonin mitigate diethylnitrosamine-instigated testicular impairment in mice: Implications of oxidative stress, spermatogenesis, steroidogenesis, and modulation of Nrf2/WT1/SF-1 signaling pathways.

AIMS: This study aimed to investigate the therapeutic influence of combination therapy with sericin and melatonin on attenuating diethylnitrosamine (DEN)-instigated testicular dysfunction in mice and defining the molecular mechanisms involved in orchestrating redox signaling pathways and restoring spermatogenesis and steroidogenesis. MATERIALS AND METHODS: Different groups of male Swiss albino mice were established and injected with respective drugs intraperitoneally. Semen analysis, hormonal assays, and oxidative stress biomarkers were evaluated. Additionally, melatonin and its receptors, WT1, SF-1, vimentin, Nrf2, and ANXA1 expressions were assessed. Histopathological and ultrastructural features of the testes were investigated by semithin, SEM, and TEM analyses. KEY FINDINGS: Exposure to DEN exhibited pathophysiological consequences, including a remarkable increase in lipid peroxidation associated with substantial diminutions in SOD, CAT, GPx, GSH, GSH:GSSG, and GST. Furthermore, it disrupted spermatozoa integrity, testosterone, FSH, LH, melatonin, and its receptors (MT1 and MT2) levels, implying spermatogenesis dysfunction. By contrast, treatment with sericin and melatonin significantly restored these disturbances. Interestingly, the combination therapy of sericin and melatonin noticeably augmented the Nrf2, WT1, and SF-1 expressions compared to DEN-treated mice, deciphering the amelioration perceived in antioxidant defense and spermatogenesis inside cells. Furthermore, immunohistochemical detection of ANXA1 alongside histopathological and ultrastructural analyses revealed evident maintenance of testicular structures without discernible inflammation or anomalies in mice administered with sericin and melatonin compared to the DEN-treated group. SIGNIFICANCE: Our findings highlighted that treatment with sericin and melatonin alleviated the testicular tissues in mice from oxidative stress and dysregulated spermatogenesis and steroidogenesis engendered by DEN.

Encapsulation of Sericin-Decorated Efficient Agents in Silk Hydrogels for Wound Dressings.

Excessive oxidative stress, bacterial infections, and inflammation are the primary factors impeding the healing of skin wounds. Bioactive hydrogels are commonly employed in the treatment of skin injuries. However, the limited solubility of many drugs and active agents in water significantly hampers their effectiveness in hydrogel dressings. In this research, prior to incorporation into the silk fibroin (SF) hydrogel matrix, two active agents curcumin and silver nanoparticles (Ag NPs) were decorated by silk sericin to improve their dispersibility and stability in water. The resultant SF/Ag/C hydrogels combined the biological safety and nontoxicity of SF, the antioxidant and anti-inflammatory efficacy of curcumin, and the antibacterial effect of Ag NPs. These properties effectively enhanced wound repair by reducing bacterial infections, mitigating oxidative stress, suppressing the expression of pro-inflammatory factors, and promoting angiogenesis. This study presented a straightforward approach for constructing bioactive hydrogels for the promotion of the wound healing process.

Sericin suppresses high glucose-induced EMT in mouse podocytes via miR-30a-5p and its target Snai1.

The effect of sericin in high glucose (HG)-induced podocyte injury and the mechanisms involving Snai1 and miR-30a-5p were investigated. Bioinformatics and dual-luciferase reporter assay evaluated the relationship of Snai1 with miR-31a-5p. Podocyte injury mouse induced by HG were randomly divided into control (5.5mmol/L D-glucose), HG (30mmol/L D-glucose), HG + Sericin (30mmol/L D-glucose+600µg/ml sericin), miR-30a-5p inhibitor NC (sericin+30mmol/L D-glucose+miR-30a-5p inhibitor negative control) and miR-30a-5p inhibitor groups (sericin+30mmol/L D-glucose+miR-30a-5p inhibitor). The migration ability of podocytes was detected by Transwell assay. The expressions of Snai1, podocin, E-cadherin, FSP-1, ZO-1, α-SMA, Desmin, and miR-30a-5p were assessed with RT-qPCR and Western blot. Snai1 was one direct target of miR-30a-5p. HG group had significantly larger number of migrated podocytes and higher levels of Snai1, FSP-1, α-SMA and Desmin, but significantly lower levels of podocin, ZO-1 and E-cadherin than control and HG + Sericin group. These effects of sericin were reversed by miR-30a-5p inhibitor, as evidenced by increased podocyte migration and increased expressions of Snai1, α-SMA, FSP-1 and Desmin, whereas decreased expressions of podocin, ZO-1 and E-cadherin. Sericin may protect podocytes from damage caused by HG via up-regulating epithelial phenotype markers, down-regulating mesenchymal phenotype markers, and reducing migration of podocytes. The mechanism may be through targeting miR-30a-5p and its target Snai1.

Sericin nano-gel agglomerates mimicking the pericellular matrix induce the condensation of mesenchymal stem cells and trigger cartilage micro-tissue formation without exogenous stimulation of growth factors in vitro.

Mesenchymal stem cells (MSCs) are excellent seed cells for cartilage tissue engineering and regenerative medicine. Though the condensation of MSCs is the first step of their differentiation into chondrocytes in skeletal development, the process is a challenge in cartilage repairing by MSCs. The pericellular matrix (PCM), a distinct region surrounding the chondrocytes, acts as an extracellular linker among cells and forms the microenvironment of chondrocytes. Inspired by this, sericin nano-gel soft-agglomerates were prepared and used as linkers to induce MSCs to assemble into micro-spheres and differentiate into cartilage-like micro-tissues without exogenous stimulation of growth factors. These sericin nano-gel soft-agglomerates are composed of sericin nano-gels prepared by the chelation of metal ions and sericin protein. The MSCs cultured on 2D culture plates self-assembled into cell-microspheres centered by sericin nano-gel agglomerates. The self-assembly progress of MSCs is superior to the traditional centrifugation to achieve MSC condensation due to its facility, friendliness to MSCs and avoidance of the side-effects of growth factors. The analysis of transcriptomic results suggested that sericin nano-gel agglomerates offered a soft mechanical stimulation to MSCs similar to that of the PCM to chondrocytes and triggered some signaling pathways as associated with MSC chondrogenesis. The strategy of utilizing biomaterials to mimic the PCM as a linker and as a mechanical micro-environment and to induce cell aggregation and trigger the differentiation of MSCs can be employed to drive 3D cellular organization and micro-tissue fabrication in vitro. These cartilage micro-masses reported in this study can be potential candidates for cartilage repairing, cellular building blocks for 3D bio-printing and a model for cartilage development and drug screening.

Silk protein sericin: a promising therapy for Achilles tendinopathy-evidence from an experimental rat model.

OBJECTIVE: This study investigated the efficacy of sericin in treating experimental Achilles tendinopathy (AT) in rats via the transforming growth factor-beta (TGF-ß)/mothers against decapentaplegic (Smad) pathway compared with diclofenac sodium (DS). METHOD: An AT model was induced in rats using collagenase enzyme type I and divided into 5 groups: C (control), AT (diseased control), ATS (AT treated with sericin), ATN (AT treated with DS), and ATSN (AT treated with sericin and DS). Sericin injection was given on the 3rd and 6th days by intratendinous injection (0.8 g/kg/mL), and DS was administered for 14 days by oral gavage (1.1 mg/kg/day). Serum concentrations of total oxidant-antioxidant status (TOS-TAS), TGF-ß1, decorin, Smad2, and connective tissue growth factor (CTGF) were measured. Histopathologic and immunohistochemical (IHC) studies were conducted on Achilles tendon samples. RESULTS: The TOS, oxidative stress index (OSI), TGF-ß1, Smad2, CTGF, and decorin serum concentrations were significantly higher in AT than in C and significantly lower in ATS than in AT (P<0.05). Histopathological examination revealed that irregular fibers, degeneration, and round cell nuclei were significantly elevated in AT. Spindle-shaped fibers were similar to those in C, and degeneration was reduced in ATS. TGF-ß1 and Smad2/3 expression was increased, and collagen type I alpha-1 (Col1A1) expression was decreased in AT vs. C (P=0.001). In the ATS, TGF-ß1 and Smad2/3 expression decreased, and Col1A1 expression increased. The Bonar score significantly increased in the AT group (P =0.001) and significantly decreased in the ATS group (P =0.027). CONCLUSION: Sericin shows potential efficacy in reducing oxidative stress and modulating the TGF-ß/Smad pathway in experimental AT models in rats. It may be a promising therapeutic agent for AT, warranting further clinical studies for validation. Key Points • This study revealed that sericin mitigates AT-induced damage through the TGF-ß/Smad pathway in an AT rat model. • ELISA and IHC investigations corroborated the effectiveness of sericin via the pivotal TGF-ß/Smad pathway in tissue repair. • Evidence indicates that sericin enhances collagen synthesis,shapes tendon fiber structure, and diminishes histopathological degeneration. • Sericin's antioxidant properties were reaffirmed in its AT treatment application.