Synthesis of melanin-like amino acid surfactant with enzymatic hydrolysates from silk degumming water.

The degummed wastewater from silk processing contains a huge amount of amino acids and polypeptides from sericin. The silk degumming water is far from being exploited fully. Sericin in the degumming water is generally wasted and causes environmental pollution. In this study, simulated silk degumming water was hydrolyzed by alkaline protease to produce abundant amino acids and polypeptides. After enzymatic hydrolysis, the maximum free amino groups concentration in the silk degumming water was approximately 54 mM. It facilitated the recycling of silk degumming water for the production of melanin-like amino acid surfactants as raw materials. 4-Tert-butylcatechol was used as the starting material to generate o-quinone via oxidation by ceric ammonium nitrate. o-Quinone was coupled with free amino groups in enzymatic hydrolysates of silk degumming water to synthesize a sericin-based amino acid surfactant as hydrophobic and hydrophilic group, respectively. Through the green and simple synthesis route, the product was characterized to have a novel melanin-like structure. The product exhibited superior surface-active properties by lowering the surface tension to 32.39 mN m-1. Furthermore, it demonstrated good foaming ability and foam stability, with the initial foam volume of 37 mL and the foam half-life time of more than 25 min. The product owned a good emulsification ability in the oil-water emulsion with delamination time of 297 s and 291 s for emulsion formed by soybean oil and liquid paraffin, respectively. The wetting time of the canvas sheet was only 134 s. Consequently, the product showed low surface tension, good foaming, emulsifying, and wetting properties.

A comparative study of sericin and gluten for magnetic nanoparticle-mediated drug delivery to breast cancer cell lines.

With breast cancer emerging as a pressing global health challenge, characterized by escalating incidence rates and geographical disparities, there is a critical need for innovative therapeutic strategies. This comprehensive research navigates the landscape of nanomedicine, specifically focusing on the potential of magnetic nanoparticles (MNPs), with magnetite (Fe3O4) taking center stage. MNPs, encapsulated in biocompatible polymers like silica known as magnetic silica nanoparticles (MSN), are augmented with phosphotungstate (PTA) for enhanced chemodynamic therapy (CDT). PTA is recognized for its dual role as a natural chelator and electron shuttle, expediting electron transfer from ferric (Fe3+) to ferrous (Fe2+) ions within nanoparticles. Additionally, protein-based charge-reversal nanocarriers like silk sericin and gluten are introduced to encapsulate (MSN-PTA) nanoparticles, offering a dynamic facet to drug delivery systems for potential revolutionization of breast cancer therapy. This study successfully formulates and characterizes protein-coated nanocapsules, specifically MSN-PTA-SER, and MSN-PTA-GLU, with optimal physicochemical attributes for drug delivery applications. The careful optimization of sericin and gluten concentrations results in finely tuned nanoparticles, showcasing uniform size, enhanced negative zeta potential, and remarkable stability. Various analyses, from Dynamic Light Scattering (DLS) and scanning electron microscopy (SEM) to transmission electron microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), X-Ray diffraction analysis (XRD), and Thermogravimetric analysis (TGA), provide insights into structural integrity and surface modifications. Vibrating Sample Magnetometer (VSM) analysis underscores superparamagnetic behavior, positioning these nanocapsules as promising candidates for targeted drug delivery. In vitro evaluations demonstrate dose-dependent inhibition of cell viability in MCF-7 and Zr-75-1 breast cancer cells, emphasizing the therapeutic potential of MSN-PTA-SER and MSN-PTA-GLU. The interplay of surface charge and pH-dependent cellular uptake highlights the robust stability and versatility of these nanocarriers in tumor microenvironment, paving the way for advancements in targeted drug delivery and personalized nanomedicine. This comparative analysis explores the suitability of silk sericin and gluten, unraveling a promising avenue for the development of advanced, targeted, and efficient breast cancer treatments.

Camellia Oleifera oil-loaded chitosan nanoparticles embedded in hydrogels as cosmeceutical products with improved biological properties and sustained drug release.

Hydrogels based on poly(vinyl alcohol), silk sericin, and gelatin containing Camellia oleifera oil (CO)-loaded chitosan nanoparticles (CSNPs) were fabricated. The loading of CO into CSNPs was achieved by a two-step procedure, which included an oil-in-water emulsion and an ionic gelation method. SEM images of CO-loaded CSNPs illustrated the spherical shape with aggregation of the nanoparticles. The particle size and polydispersity index were 541-1089 nm and 0.39-0.65, respectively. The encapsulation efficiency and loading capacity were 3-16 % and 4-6 %, respectively. The gelatin/poly(vinyl alcohol)/sericin hydrogels were fabricated and incorporated with CO or CO-loaded CSNPs with different concentrations of CO-loaded CSNPs. All hydrogels demonstrated a porous structure. Besides, the hydrogels containing CO-loaded CSNPs showed a more controlled and sustained release profile than the hydrogels containing CO. Moreover, the hydrogels showed tyrosinase inhibition (9-13 %) and antioxidant activity (37-60 %). Finally, the hydrogels containing CO-loaded CSNPs were non-toxic to the Normal Human Dermal Fibroblasts and NCTC clone 929 cells, even at a high dosage of 50 mg/mL. As a result, these hydrogels exhibited excellent potential for use in cosmeceutical industries.

Advancements in silk fibroin and silk sericin-based biomaterial applications for cancer therapy and wound dressing formulation: A comprehensive review.

Silks are a class of proteins generated naturally by different arthropods, including silkworms, spiders, scorpions, mites, wasps, and bees. This review discusses the silk fibroin and silk sericin fabricated by Bombyx mori silkworm as versatile fibers. This silk fiber is predominantly composed of hydrophobic silk fibroin and hydrophilic silk sericin. Fibroin is defined as a structural protein that bestows silk with strength, while sericin is characterized as a gum-like protein, tying the two fibrous proteins together and endowing silk proteins with elasticity. Due to their versatile structures, biocompatibility, and biodegradability, they could be tailored into intricate structures to warrant particular demands. The intrinsic functional groups of both proteins enable their functionalization and cross-linking with various biomaterials to endow the matrix with favorable antioxidant and antibacterial properties. Depending on the target applications, they can be integrated with other materials to formulate nanofibrous, hydrogels, films, and micro-nanoparticles. Given the outstanding biological and controllable physicochemical features of fibroin and sericin, they could be exploited in pharmaceutical applications involving tissue engineering, wound repair, drug delivery, and cancer therapy. This review comprehensively discusses the advancements in the implementation of different formulations of silk fibroin and sericin in wound healing and drug delivery systems, particularly for cancer treatment.

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.

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 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.

[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.

Inclusion of reeling wastewater-derived sericin peptides in high-protein nutrition bars for antihardening and storage stability.

The utilization of agroindustrial wastes to enrich food protein resources and the exploration of their broader applications are crucial for addressing the food crisis and achieving sustainable development goals. In this study, reeling wastewater-derived sericin was hydrolyzed using papain and trypsin to prepare sericin peptide (SRP) and was used as an antihardening ingredient of high-protein nutrition bars (HPNBs). The mechanism of the antihardening effect of SRP was elucidated by investigating the content of advanced glycation end products and protein oxidation products (carbonyl and free sulfhydryl), and the molecular weight change of HPNBs during storage before and after the addition of SRP. Our results confirmed the fortification of HPNBs with SRP, which is beneficial for the promotion and expansion of sericin applications in the food industry, with positive implications for the rational utilization of protein resources and the enrichment of food protein sources.

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.

Synergistic effects of thyme and oregano essential oil combinations for enhanced functional properties of sericin/pectin film.

This work aimed to assess the synergistic antibacterial effects of thyme and oregano essential oils in various ratios (thyme:oregano; 10:0, 8:2, 6:4, 4:6, 2:8, 10:0). We hypothesized that the synergistic combination of thyme and oregano essential oils can be effectively incorporated into sericin/pectin film to enhance its functional properties. Among the combinations tested, the mixture of thyme/oregano essential oil (TOE) at an 8:2 ratio exhibited the most potent synergistic activity against P. aeruginosa and S. aureus, with fractional inhibitory concentration index (FICindex) of 0.9. In this combination, thymol constituting 51.83 % of TOE (8:2), was the predominant component. TOE at an 8:2 ratio was selected to incorporate into sericin/pectin film. Different concentrations of TOE (0.8 %, 1.2 % and 1.6 %) were applied to evaluate their impact on film properties compared to a film without essential oil (control). It was found that increasing TOE concentration (control; 0 %) to 1.6 % reduced film moisture content (from 21.53 % to 16.91 %), decreased yellowness (from 18.24 to 15.92), diminished gloss (from 63.79 to 11.18), lowered swelling index (from 1.24 to 0.98), and reduced tensile strength (from 9.70 to 4.14 MPa). However, the addition of TOE showed higher film total phenolic content (8.59-31.53 mg gallic acid/g dry sample) and increased antioxidant activity (0.99-3.68 µmol Trolox /g dry sample). Moreover, the film with 1.2 % and 1.6 % of thyme/oregano essential oil exhibited inhibitory effects against all tested bacteria. Therefore, the thyme/oregano essential oil combination can provide the desirable physicochemical properties of the sericin/pectin film, as well as its antibacterial and antioxidant activities, making it a promising alternative for food packaging material applications.

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.

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.

Toxicological effects of dimethlybenzeneanthracene in Balb C mice and pharmacological intervention by silk sericin-conjugated silver nanoparticles.

Polycyclic aromatic hydrocarbons (PAHs) such as 7, 12-dimethylbenzneanthracene (DMBA), due to long-term bioaccumulation cause serious physiological processes and behavioral dysfunctions such as cancer, ageing, and hypertension. Silk sericin (SS) is instrumental in cancer applications due to presence of flavonoids and carotenoids which are natural pigments, present in the layer of sericin that has antioxidant and antityrosinase activity. It reduces oxidative stress and suppresses cancer cytokines while interacting with reactive oxygen species (ROS) to stand against lipid peroxidation. Recent research was focused to calculate the pharmacological intervention of sericin-conjugated silver nanoparticles (S-AgNO3 NPs) against DMBA-induced toxicity. For this purpose, SS protein was extracted from silkworm cocoons by degumming process and the prepared S-AgNO3 NPs via a green synthesis. In female albino mice, a total of 50 mg/kg oral administration of DMBA was used for the induction of toxicity which required almost 8 to 10 weeks approximately. After 60 days of experimentation, mice were dissected, blood samples were collected for further hematological and biochemical analysis and were euthanized via cervical dislocation. There was a significant rise in the level of red blood cells, platelets, lymphocytes, and hemoglobin at the highest applied concentration of sericin and its nanoparticles. Similarly, a reasonable decline was observed in the level of white blood cells, neutrophils, eosinophils, and monocytes as compared to the cancer-inducing group. The level of glutathione, lactate dehydrogenase, and alkaline phosphatase as well as immunoglobulins such as immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) were significantly reduced in all treatment groups as compared to the DMBA-induced group. Substantial effects were demonstrated in response to S-AgNO3 NPs II (T) at the highest concentrations (200 mg/kg, BW) as follows: glutathione (2.42 ± 0.26 µmol/L), lactate dehydrogenase (493.6 ± 5.78 U/L), alkaline phosphatase (158.4 ± 6.35 U/L), IgA (4.22 ± 0.19 g/L), IgG (70 ± 1.70 g/L), and IgM (4.76 ± 0.12). The histopathological study of the liver, kidneys, and brain revealed that the DMBA-induced group showed cytotoxic effects against all selected organs of mice that were recovered by treatment of selective compounds but highly effective recovery was seen in S-AgNO3 NPs II (T). These results concluded that silk S-AgNO3 NPs showed significant pharmacological potential against cancer-inducing toxicity.

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.

Exploring the apoptotic effects of sericin on HCT116 cells through comprehensive nanostring transcriptomics and proteomics analysis.

Sericin, a silk protein from Bombyx mori (silkworms), has many applications, including cosmetics, anti-inflammation, and anti-cancer. Sericin complexes with nanoparticles have shown promise for breast cancer cell lines. Apoptosis, a programmed cell death mechanism, stops cancer cell growth. This study found that Sericin urea extract significantly affected HCT116 cell viability (IC50 = 42.00 ± 0.002 µg/mL) and caused apoptosis in over 80% of treated cells. S-FTIR analysis showed significant changes in Sericin-treated cells' macromolecule composition, particularly in the lipid and nucleic acid areas, indicating major cellular modifications. A transcriptomics study found upregulation of the apoptotic signaling genes FASLG, TNFSF10, CASP3, CASP7, CASP8, and CASP10. Early apoptotic proteins also showed that BAD, AKT, CASP9, p53, and CASP8 were significantly upregulated. A proteomics study illuminated Sericin-treated cells' altered protein patterns. Our results show that Sericin activated the extrinsic apoptosis pathway via the caspase cascade (CASP8/10 and CASP3/7) and the death receptor pathway, involving TNFSF10 or FASLG, in HCT116 cells. Upregulation of p53 increases CASP8, which activates CASP3 and causes HCT116 cell death. This multi-omics study illuminates the molecular mechanisms of Sericin-induced apoptosis, sheds light on its potential cancer treatment applications, and helps us understand the complex relationship between silk-derived proteins and cellular processes.

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.

Sericin Improves Memory Impairment Via Activation of the PKA-CREB-BDNF Signaling Pathway and Suppression of Oxidative Stress in Ovariectomized Mice.

Menopause results in estrogen hormone deficiency which causes changes in brain morphology and cognitive impairments. The risk of breast and ovarian cancer increases with estrogen therapy. Thus, finding a substitute treatment option for women in menopause is necessary. In the current study, the impact of chronic sericin treatment (200 mg/kg/day for 6 weeks, gavage) on memory process, oxidative stress markers, synaptic neurotransmission, and acetylcholinesterase (AChE) activity in the hippocampus (HIP) of ovariectomized (OVX) mice was examined and compared to the effects of 17ß-estradiol (Es; 20 µg/kg, s.c.). The results demonstrated that sericin and Es administration improved spatial and recognition memory of the OVX animals in the both Lashley III maze and novel object recognition tests. Moreover, sericin-treated OVX mice showed decreased ROS levels, increased endogenous antioxidant defense capacity, and decreased AChE activity in the HIP. Additionally, sericin and Es therapy up-regulated pre-and-post-synaptic protein markers and increased BDNF, CREB, and protein kinase A (PKA) protein expressions in the HIP of OVX mice. Overall, the activation of the PKA-CREB-BDNF signaling pathway by sericin can provide protection against OVX-induced cognitive dysfunction, making it a potential alternative for managing cognitive deficits in postmenopausal women.

Mn-Anti-CTLA4-CREKA-Sericin Nanotheragnostics for Enhanced Magnetic Resonance Imaging and Tumor Immunotherapy.

The integration of magnetic resonance imaging (MRI), cGAS-STING, and anti-CTLA-4 (aCTLA-4) based immunotherapy offers new opportunities for tumor precision therapy. However, the precise delivery of aCTLA-4 and manganese (Mn), an activator of cGAS, to tumors remains a major challenge for enhanced MRI and active immunotherapy. Herein, a theragnostic nanosphere Mn-CREKA-aCTLA-4-SS (MCCS) is prepared by covalently assembling Mn2+, silk sericin (SS), pentapeptide CREKA, and aCTLA-4. MCCS are stable with an average size of 160 nm and is almost negatively charged or neutral at pH 5.5/7.4. T1-weighted images showed MCCS actively targeted tumors to improve the relaxation rate r1 and contrast time of MRI. This studies demonstrated MCCS raises reactive oxygen species levels, activates the cGAS-STING pathway, stimulates effectors CD8+ and CD80+ T cells, reduces regulatory T cell numbers, and increases IFN-γ and granzyme secretion, thereby inducing tumor cells autophagy and apoptosis in vitro and in vivo. Also, MCCS are biocompatible and biosafe. These studies show the great potential of Mn-/SS-based integrative material MCCS for precision and personalized tumor nanotheragnostics.

Sericin alleviates motor dysfunction by modulating inflammation and TrkB/BDNF signaling pathway in the rotenone-induced Parkinson's disease model.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of nigrostriatal dopaminergic neurons and movement impairment. Based on theories, neuroinflammatory processes may be vital in the etiology of PD and other neurodegenerative diseases. Reports show that rotenone has neurotoxic, inflammatory, and motor impairment effects in PD. Sericin is a natural polymer with effective properties, such as neuroprotective and anti-inflammatory. Therefore, this study aimed to examine the effects of sericin administration on motor dysfunction by modulating inflammation and tyrosine kinase B/brain-derived neurotrophic factor (TrkB/BDNF) pathway in the rotenone-induced PD model. METHODS: Wistar male rats (3-months-old) were treated with rotenone (2 mg/kg every 48 h for 30 days) to induce a rotenone-induced PD model. Also, sericin was administered orally at dose of 200 mg/kg every 48 h for 30 days. Rotarod and bar tests were performed for motor dysfunction. The protein levels of BDNF, c-fos, TrkB, tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6) and catalase activity were evaluated in the striatum area. RESULTS: Results showed that sericin increased latent time in the rotarod test and decreased the time staying on the pole in the bar test compared to the PD group (P < 0.001 for both tests). Moreover, sericin treatments decreased TNF-α (P < 0.001) and IL-6 (P < 0.001) concentration levels and enhanced the levels of BDNF (P < 0.001), c-fos (P < 0.001), TrkB (P < 0.001) proteins and catalase activity (P < 0.05) in the striatum area compared to the PD group. CONCLUSION: These results support a protective benefit of sericin therapy in a rotenone-induced PD paradigm by reducing motor impairment, inflammatory response, and disruption of the TrkB/BDNF signaling pathway.