The therapeutic efficacy of chemotherapy in solid tumors such as osteosarcoma is hindered by the dense, collagen-rich extracellular matrix (ECM). In this work, we report an acid-responsive nanogel that co-encapsulates bromelain (BL), a proteolytic enzyme, and doxorubicin (DOX) with spatially distinct localization and independent pH-responsive release mechanisms. BL is encapsulated within the nanogel network, whereas DOX is covalently grafted onto the nanogel surface via an acid-labile linker, enabling the nanocarrier (ng(BL–DOX)) to remain stable under physiological conditions while promoting controlled release in the mildly acidic tumor microenvironment. The released BL degrades collagenous ECM components and reduces matrix density, thereby improving the penetration and intratumoral distribution of the concurrently released DOX. In a murine osteosarcoma model, the PEG-rich nanogels showed prolonged circulation and increased tumor accumulation via the enhanced permeability and retention (EPR) effect, accompanied by collagen I degradation and effective tumor growth inhibition, with final tumor volumes reduced to approximately one-tenth of those in the control group and without observable systemic toxicity. This microencapsulation approach provides an enzyme–drug co- encapsulation system that combines ECM degradation with chemotherapy in a single nanogel platform and may be adapted to other proteolytic enzymes and cytotoxic agents for the treatment of stroma-rich solid tumors.

Enhanced production of stem bromelain in Pichia pastoris by coexpression of unfolded protein response activator gene HAC1P.

Sleep deprivation (SD) significantly disrupts intestinal homeostasis and causes intestinal damage. Previous research conducted by our group has demonstrated that SD induces intestinal damage through intestinal hypoxia. Intestinal hypoxia is closely associated with ischemia. In this study, we found that bromelain (BR), a compound with anticoagulant and anti-inflammatory properties, mitigated SD-induced intestinal damage, and restored blood perfusion and clotting function. Mechanistically, we identified 5-HT as a key mediator during SD, and BR reduced 5-HT levels by inhibiting TRPA1-mediated calcium influx in Enterochromaffin (EC) cells. These findings define the TRPA1-5-HT axis as a novel therapeutic target for sleep disorder-related gastrointestinal pathologies and mechanistically expand BR's therapeutic potential from anticoagulation to direct modulation of 5-HT via calcium-dependent inhibition of TRPA1.

BackgroundThis study aims to evaluate the compressive strength, solubility, radiopacity, and flow of Bromelain (BR)-modified Biodentine (BD) for direct pulp capping (DPC). This is suggested to determine the impact of BR on the physical properties of BD.MethodsEighty samples were prepared according to the ISO and ADA specifications and evaluated for compressive strength, solubility, radiopacity, and flow. The compressive strength was evaluated at 24 h and 21 days via a universal testing machine. The solubility was determined by weight loss after 24-hours immersion in deionized water. Radiopacity was assessed via X-ray with aluminum step-wedges, and flow was measured by the diameter of the discs under a standard weight. Independent sample t-tests were used to statistically assess the data. A significance level of 5% was considered.ResultsThe compressive strength was 41.08 ± 1.84 MPa for BD and 40.92 ± 1.80 MPa for BR + BD after 24 h, and 88.93 ± 3.39 MPa for BD and 87.92 ± 3.76 MPa for BR + BD after 21 days, with no significant differences. Solubility was slightly greater in the BR + BD (2.75 ± 0.10%) compared to BD (2.62 ± 0.25%), but not significantly different. The radiopacity was similar between BD (2.82 ± 0.11 mm) and BR + BD (2.73 ± 0.10 mm). BR + BD resulted in significantly greater flow (9.99 ± 0.18 mm) than did BD (9.65 ± 0.27 mm) (p ≤ 0.05).ConclusionBR-modified BD maintains BD’s physical properties, with improved flow, making it a promising DPC agent that warrants further study.

Addressing the interaction of stem bromelain with different anionic surfactants, below, at and above the critical micelle concentration (cmc) in phosphate buffer at pH 7: Physicochemical, spectroscopic, & molecular docking study

Fried foods are favored for their unique crispiness, golden color and flavor, but they also face great challenge because of their high oil content, high calories and the existence of compounds such as acrylamide and polycyclic aromatic hydrocarbons. Long-term consumption of fried foods may adversely affect health. Therefore, it is necessary to explore fried foods with lower oil contents and a high quality to meet the demand. A method of enzyme treatment was explored to investigate the effects of maltogenic amylase (MA), transglutaminase (TG) and bromelain (BRO) on the physicochemical properties of the batter and the quality of fried spring roll wrapper (FSRW). The results showed that the MA-, TG- or BRO-treated batters had a significant shear-thinning behavior, especially with an increase in viscosity upon increasing TG contents. FSRW enhanced its fracturability from 419.19 g (Control) to 616.50 g (MA-6 U g-1), 623.49 g (TG-0.75 U g-1) and 644.96 g (BRO-10 U g-1). Meanwhile, in comparison with BRO and MA, TG-0.5 U g-1 endowed batter with the highest density and thermal stability. MA-15 U g-1 and TG-0.5 U g-1 displayed FSRW with uniform and dense pores, and significantly reduced its oil content by 18.05% and 25.02%, respectively. Moreover, compared to MA and TG, BRO-50 U g-1 improved the flavor of FSRW. MA, TG or BRO played a key role in affecting the physicochemical properties of the batter and the quality of FSRW. TG-0.5 U g-1 remarkly reduced the oil content of FSRW with a great potential in practical application. © 2024 Society of Chemical Industry.

Bilayer fiber membrane electrospun from polylactic acid/alginate/bromelain and polylactic acid for enhancing the functionality of tea bags

Bromelain-loaded silver nanoparticles: Formulation, characterization and biological activity

The emergence of acute hepatopancreatic necrosis disease (AHPND) caused by pathogenic strains of Vibrio parahaemolyticus (VPAHPND) had economically impacted shrimp farmers. There is great interest in using phytogenics as antibiotic alternatives in mitigating bacterial diseases. A 28‐day feeding trial using quadruplicate groups of Penaeus vannamei was conducted to evaluate the efficacy of bromelain (BM), a pineapple extract, on growth, gut microbiota, and resistance to AHPND. Dietary 1% or 2% BM enhanced growth of shrimp, which was significantly (P < 0.05) higher at 2% BM compared to control (0% BM). In the first AHPND challenge, shrimp survival (mean ± SE) fed 1% or 2% BM were 84.8% ± 3.8% and 78.3% ± 2.5%, respectively, and significantly higher compared to the positive control group (69.6% ± 1.8%). Surviving shrimp were then regrouped into triplicates and fed the control diet for 14 days. This wash‐out period was used to determine if prior dietary BM had a longer‐term effect on shrimp health. In the second AHPND challenge, shrimp survival previously fed 1% or 2% BM was 71.1% ± 9.7% and 73.3% ± 3.8%, respectively, and significantly higher compared to the control group (51.1% ± 2.2%). Hepatopancreas showed less damage and harbored significantly lower Vibrio counts in shrimp fed BM‐added diets. Dietary BM modulated the stomach bacterial community and imparted the highest alpha diversity. At the phylum level, Proteobacteria, Actinobacteria, and Bacteroidetes were the main groups across treatments but with varying relative abundance. Luteolibacter, Paracoccus, Planctomyces, and Demequina were identified as the main contributors for the diversity differences observed among treatment groups. The relative abundance of Luteolibacter was significantly enriched and Vibrio bacteria significantly lowered in the stomach of the BM‐added groups. It was concluded that dietary BM induced modulation of the stomach microbiota of shrimp, which potentially enhanced its resistance to AHPND‐causing VP.

A new bioamphiphile sodium-2-decanamyde-2-methyl propanoate (SDMP) was synthesized to study the photophysical properties of bromelain (BM) in its micellar medium, and with the addition of RTILs, SDS, NaCl and NOT using spectroscopic methods.

Controlling the size, shape, and stability of SeNPs by bromelain: Improved antioxidant, anti-bacterial and anti-cancer activities

A cutaneous wound is caused by various injuries in the skin, which can be wrapped with an efficient dressing. Electrospinning is a straightforward adjustable technique that quickly and continuously generates nanofibrous wound dressings containing antibacterial and anti-inflammatory agents to promote wound healing. The present study investigated the physicochemical and biological properties of bromelain (BRO)- and silver nanoparticle (Ag NPs)-loaded gel-based electrospun polycaprolactone/chitosan (PCL/CS) nanofibrous dressings for wound-healing applications. Electron microscopy results showed that the obtained nanofibers (NFs) had a uniform and homogeneous morphology without beads with an average diameter of 176 ± 63 nm. The FTIR (Fourier transform infrared) analysis exhibited the loading of the components. Moreover, adding BRO and Ag NPs increased the tensile strength of the NFs up to 4.59 MPa. BRO and Ag NPs did not significantly affect the hydrophilicity and toxicity of the obtained wound dressing; however, the antibacterial activity against E. coli and S. aureus bacteria was significantly improved. The in vivo study showed that the wound dressing containing BRO and Ag NPs improved the wound-healing process within one week compared to other groups. Therefore, gel-based PCL/CS nanofibrous dressings containing BRO and Ag NPs could be a promising solution for healing skin wounds.

Gastric ulcer is one of the most common diseases of the gastrointestinal system and some of its complications are the main causes of morbidity and mortality. Bromelain (BRM), a sulfhydryl proteolytic enzyme, has multiple activities in many areas of medicine as an antioxidant and anti-inflammatory agent. In this study, it was aimed to investigate the anti-inflammatory and oxidative stress-mediated therapeutic effect of BRM in a gastric ulcer model induced by indomethacin (IND) which is a non-steroidal anti-inflammatory drug (NSAID) with gastric ulcer-forming effects. Gastric mucosal paraoxonase (PON), arylesterase (ARE), catalase (CAT), myeloperoxidase (MPO) and glutathione peroxidase (GPx) activity and total glutathione (GSH) levels were analyzed. Interleukin-33 (IL-33), the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) levels were determined by immunohistochemically. Although IND-induced histopathological changes occurred, BRM pretreatment prevented these effects. As a result of the study, it was determined that BRM had an anti-ulcerative effect at a dose of 50 mg/kg. BRM given at this dose significantly decreased gastric tissue MPO activity, and increased CAT, PON, ARE, GPx activity and GSH level. The increased IL-33 and decreased Nrf-2 and HO-1 levels were obtained in IND group and these changes were reversed by BRM. As a result, it was concluded that BRM may have protective effects in IND-induced gastric model by reducing inflammation and regulating oxidant/antioxidant balance.

MP27-06 BROMELAIN INDUCES RELAXATION OF HUMAN CORPUS CAVERNOSUM TISSUE <i>IN VITRO</i> INDEPENDENT NITRIC OXIDE-CGMP PATHWAY: POSSIBLE SIGNIFICANCE FOR ERECTILE DYSFUNCTION

Bromelain (BRN) is an extensive product of investigation, regarded as eff ective naturally produced anticancer agents. Heterogeneity of tumors amongst patients and within disease, generates a necessity of personalization of nanomedicine. The size of nanoparticle is found to be a signifi cant target in enhancing precision therapeutics, by fondly accumulate it within the tumor microenvironment. The objective of the study is to achieve an optimum size of 50 to 100 nm BRN loaded nano carriers, to intensify the EPR eff ect and thereby overcome heterogeneity. Optimization of the nanoparticles commenced with the interrogation of eff ect by various formulation variables. The development of nanoparticles carried out by the nanoprecipitation method, where three independent variables, such as the amount of PLGA, Tween 80 and BRN are chosen after an overall screening and employed in Design Expert Software. The selected Box-Behnken design provides a total of 17 confi rmatory runs at varied levels of independent variables and detected its infl uence on responses. The runs resulted in an optimized formula with the desired particle size of 78.64 ± 2.14 nm and a maximum entrapment effi ciency of 89.14% at 24th hour. Then the selected formula characterized for polydispersity index, zeta potential, sanning electron m icroscopy, determination of drug content, study of in-vitro drug release etc.

Enhanced photothermal and chemotherapy of pancreatic tumors by degrading the extracellular matrix

Metabolic syndrome (MS) is considered a major public health problem because it is associated with the development of cardiovascular disease and type 2 diabetes. Bioactive peptides can play an important role in the prevention and treatment of MS. The possible health effects of peptides obtained from hydrolysed chicken by-products (CH) by the action of plant proteases from Bromelia pinguin (BP), B. karatas (BK), and bromelain (BRO) were evaluated in a model of induced MS. Thirty male Wistar rats were randomised into the following groups: (1) standard diet (STD); (2) induction of MS with a hypercaloric diet (MS+CH); (3) CH-BP 200 mg CH/kg; (4) CH-BK 200 mg CH/kg; (5) CH-BRO 200 mg CH/kg; and (6) carnosine (CAR) 50 mg of carnosine/kg of body weight. The CH decreased the glucose levels (p &lt; 0.05) and improved the lipid profile (p &lt; 0.05) in the serum of the groups with induced MS. Liver lesions were attenuated with a decrease in hepatic enzymatic activities (p &lt; 0.05), and the accumulation of lipid inclusions in the liver decreased. The data showed that CH and the use of proteases to obtain peptides with health effects could be a good therapeutic alternative for individuals with MS.

Effects of p-sulfonatocalixarene and p-sulfonatocalixarene/sulfobetaine surfactant complex on the activities of bromelain and polyphenol oxidase

Many studies have revealed the prominent roles of mast cells in wound healing, including inflammatory reactions, angiogenesis and extracellular matrix reabsorption. In the present study, we aimed to assess the probable therapeutic features of bromelain on wound contraction and mast cell degranulation in wound healing in experimental diabetic animals. Male rats were grouped as control, vehicle and experiment. Skin wounds were generated in all groups. Treatments were applied with distilled water and with bromelain (BR) intraperitoneally in the vehicle and experimental groups, respectively. Following skin wound generation, animals were euthanised on days 3, 5, 7 and 15. We gathered 16,800 microscopic images to count the mast cells and degranulation level (Image J software). The wound contraction index was assessed both microscopically (Image J software) and macroscopically (time-lapse photography). The meshwork evaluation method was used to assess wound healing. Time-lapse photography revealed that the BR significantly (p<0.05) accelerated wound contraction and healing. BR significantly (p<0.05) increased the total number of mast cells in all experimental groups on days 5 and 7. The count of grade III (degranulated) mast cells was reduced significantly (p<0.05) on days 5 and 7 in experimental groups compared to control and vehicle groups. In this study, the rate of wound healing was accelerated considerably following BR administration. In addition, this agent decreased the count of degranulated mast cells, leading to wound contraction and healing.

Objective: The goal of this study was to look into whether bromelain (BRM) could protect against methotrexate (MTX)-induced kidney and liver damage. Material and Method: The rats were divided into four groups (n=7); the control group was given distilled water by gavage for 14 days and intraperitoneal (i.p.) physiological saline (%0.9 NaCI) on the third day; the BRM group was given 200 mg/kg BRM by gavage for 14 days and i.p. physiological saline (%0.9 NaCI) on third day; the MTX group was given distilled water by gavage for 14 days and i.p. single dose of 20 mg/kg MTX on the third day; the MTX+BRM group was given 200 mg/kg BRM by gavage for 14 days and i.p. single dose of 20 mg/kg MTX on the third day. Rats were decapitated at the end of the experiment, kidney and liver tissues were kept at -80°C, and biochemical analyzes were performed on the supernatants obtained from tissue homo-gentates. Results: With the administration of MTX, oxidation indicator thiobarbituric acid reactive substance (TBARS) levels increased in comparison with the control group; antioxidants- glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities were decreased compared to the control group. Co-administration of BRM with MTX resulted in reduction in TBARS level and increase in GSH, CAT, SOD, and GPx activities. Conclusion: In this study, it was determined that MTX caused oxidative damage in kidney and liver tissues and BRM prevented this damage.