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Background: Stem cell-laden hydrogel microcapsules construction is important for a wide application in tissue engineering and cell-based medicine, such as building an ideal immune barrier. Challenges are emerging for effectively storing such microcapsules by cryopreservation, and a large proportion of research has been on the cryopreservation of single cells encapsulated into microcapsules without a core-shell structure., Objective: To achieve the effective cryopreservation of stem cell-laden hydrogel microcapsules with a core-shell structure., Materials and Methods: A novel core-shell alginate hydrogel encapsulation method was used to produce mesenchymal stem cell-laden microcapsules by microfluidic technique., Results: This microcapsule could inhibit ice formation to achieve vitreous cryopreservation with a low concentration (2 M) of penetrating cryoprotectants., Conclusion: Cell laden hydrogel microcapsules may have the potential to be the basis of a new strategy of cell cryopreservation and applications. https://doi.org/10.54680/fr24210110212.

Although mitochondria are crucial for recovery after spinal cord injury (SCI), therapeutic strategies to modulate mitochondrial metabolic energy to coordinate the immune response and nerve regeneration are lacking. Here, a ligand-screened cerium-based metal-organic framework (MOF) with better ROS scavenging and drug-loading abilities is encapsulated with polydopamine after loading creatine to obtain microcapsules (Cr/Ce@PDA nanoparticles), which reverse the energy deficits in both macrophages and neuronal cells by combining ROS scavenging and energy supplementation. It reprogrames inflammatory macrophages to the proregenerative phenotype via the succinate/HIF-1α/IL-1β signaling axis. It also promotes the regeneration and differentiation of neural cells by activating the mTOR pathway and paracrine function of macrophages. In vivo experiments further confirm the effect of the microcapsules in regulating early ROS-inflammation positive-feedback chain reactions and continuously promoting nerve regeneration. This study provides a new strategy for correcting mitochondrial energy deficiency in the immune response and nerve regeneration following SCI., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Dyslipidemia is an imbalance of various lipids, and propolis, as a natural resinous viscos mixture made by Apis mellifera L. could improve in this condition. In this single-blind, randomized trial, 60 women with type 2 diabetes and dyslipidemia were divided into four groups: (1) the patients who did not apply the combined training and 500 mg propolis capsules supplement (Control group); (2) subjects performed combined training, including aerobic and resistance training (EXR); (3) subjects received the 500 mg propolis supplement capsules (SUPP); (4) Subjects performed combined training along with receiving the 500 mg propolis supplement capsules (EXR + SUPP). We evaluated the concentration of CTRP12, SFRP5, interleukin-6 (IL6), superoxide dismutase (SOD), malondialdehyde (MDA), adiponectin, and total antioxidant capacity (TAC) before and after the intervention. MDA, TAC, IL6, CTRP12, SFRP5 IL6, adiponectin, and lipid profile levels ameliorated in the EXR + SUPP group. We found that 8 weeks of treatment by combined exercise training and propolis supplement decreased inflammation activity and increased antioxidant defense in women with diabetic dyslipidemia.Trial registration This study was registered in the Iranian Registry of Clinical Trials; IRCT code: IRCT20211229053561N1., (© 2023. The Physiological Society of Japan.)

Improved therapies for inflammatory bowel diseases are sorely needed. Novel therapeutic agents and the development of controlled release systems for targeted tissue delivery are interesting approaches to overcome these barriers. We investigated the activity of trans-chalcone (T) in acetic acid-induced colitis in mice and developed, characterized, and determined the therapeutic effect of pectin/casein polymer microcapsules containing T (MT) in a colitis mouse model. In vitro, compound release was achieved in simulated intestinal fluid but not in the simulated gastric fluid. In vivo, since T at the dose of 3 mg/kg but not 0.3 mg/kg ameliorated colitis, we next tested the effects of MT at 0.3 mg/kg (non-effective dose). MT, but not free T at 0.3 mg/kg, significantly improved colitis outcomes such as neutrophil recruitment, antioxidant capacity, cytokine production, and NF-kB activation. This translated into reduced macro and microscopic damage in the colon. T release from the microcapsules is mediated by a pH-dependent and pectinase-regulated mechanism that provide controlled and prolonged release of T. Moreover, MT lowered the required dose for T therapeutic effect, indicating that could be a suitable pharmaceutical approach to colitis treatment. This is the first demonstration that T or MT is effective at reducing the signs of colitis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Blocking of nutrient uptake and amino acid biosynthesis are considered potential targets for next-generation antifungal drugs against pathogenic fungi, including Cryptococcus neoformans. In this regard, the sulfate assimilation pathway is particularly attractive, as it is only present in eukaryotes such as plants and fungi, yet not in mammals. Here, we demonstrated that the adenylyl sulfate kinase (Met14) in the sulfate assimilation pathway is not essential yet is required for the viability of C. neoformans due to its involvement in biosynthesis of two sulfur-containing amino acids, cysteine and methionine. Met14-dependent cysteine and methionine biosynthesis was found to significantly contribute to a diverse range of pathobiological processes in C. neoformans. Met14-dependent cysteine rather than methionine biosynthesis was also found to play pivotal roles in cell growth and tolerance to environmental stresses and antifungal drugs. In contrast, the Met14-dependent methionine biosynthesis was found to be more important than cysteine biosynthesis for the production of major cryptococcal virulence factors of melanin pigments and polysaccharide capsules. Finally, we also found that despite its attenuated virulence in an insect model, Galleria mellonella, the met14 Δ mutant yielded no difference in virulence in a murine model of systemic cryptococcosis. Hence, clinical inhibition of Met14-dependent amino acid biosynthetic pathways may not be advantageous for the treatment of systemic cryptococcosis. IMPORTANCE Current antifungal drugs have several limitations, such as drug resistance, severe side effects, and a narrow spectrum. Therefore, novel antifungal targets are urgently needed. To this end, fungal sulfur amino acid biosynthetic pathways are considered potential targets for development of new antifungal agents. Here, we demonstrated that Met14 in the sulfate assimilation pathway promotes growth, stress response, and virulence factor production in C. neoformans via synthesis of sulfur-containing amino acids methionine and cysteine. Met14-dependent cysteine rather than methionine synthesis was found to be critical for growth and stress responses, whereas Met14-dependent methionine synthesis was more important for the production of antiphagocytic capsules and antioxidant melanin in C. neoformans. Surprisingly, deletion of the MET14 gene was found to attenuate cryptococcal virulence in an insect model, yet not in a murine model. Collectively, our results showed that Met14-dependent cysteine and methionine biosynthesis play roles that are distinct from each other in C. neoformans. Moreover, Met14 is unlikely to be a suitable anticryptococcal drug target., Competing Interests: The authors declare no conflict of interest.

Objective: In this study, it was aimed to provide a therapeutic approach for T1DM by encapsulating the pancreatic islets with mesenchymal stem cells and decellularized pancreatic extracellular matrix to support the survival of islets while maintaining their cellular activity., Method: Pancreatic extracellular matrix was decellularized using different concentrations of detergent series. After the preparation of the protein-based tissue extracellular matrix was shown to be free of cells or any genetic material by molecular, immunofluorescence and histochemical techniques. Following the homogenization of the decellularized pancreatic extracellular matrix and the analysis of its protein composition by LC-MS, the matrix proteins were incorporated with pancreatic islets and rat adipose tissue-derived MSCs (rAT-MSCs) in alginate microcapsules. Glucose-stimulated insulin secretion property of the islet cells in the microbeads was evaluated by insulin ELISA. The gene expression profile of the encapsulated cells was analyzed by Real-Time PCR., Results: Unlike the protein composition of whole pancreatic tissue, the decellularized pancreas matrix was free of histone proteins or proteins originated from mitochondria. The protein matrix derived from pancreatic tissue was shown to support the growth and maintenance of the islet cells. When compared to the non-encapsulated pancreatic islet, the encapsulated cells demonstrate to be more efficient in terms of insulin expression., Conclusion: The extracellular pancreatic matrix obtained in this study was directly used as supplementary in the alginate-based microcapsule enhancing the cell survival. The tissue matrix protein and alginate had a synergistic effect on total insulin secretion, which might have the potential to overcome the insulin deficiency. Despite the improvement in the cell viability and the number, the efficiency of the insulin secretion in response to glucose stimulation from the alginate microcapsules did not meet the expectation when compared with the non-encapsulated pancreatic islets., Competing Interests: Disclosure of interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

One of the complications of menopause is sleep disorders, which affect women's health. Ocimum basilicum contains compounds that may affect sleep. The aim of this study was to determine the effect of an oral capsule of O. basilicum leaf extract on sleep quality and the severity of insomnia in menopausal women. This triple-blind, randomized clinical trial study was performed on 60 Iranian menopausal women aged 40 to 65 years. Subjects were randomly assigned into two groups of intervention (each capsule containing 250 mg of O. basilicum extract and 250 mg Avicel) per day for 1 month and placebo. The Pittsburgh Sleep Quality and Insomnia Intensity Index were used to assess sleep quality and severity of insomnia before, 2 weeks after and 1 month after the intervention. There was no statistically significant difference in the baseline variables between the intervention and placebo groups (p > .05). The total sleep quality scores in the two groups of intervention and placebo were 6.2 ± 0.3 versus 9.3 ± 0.3 (p < .001) and 3.7 ± 0.3 versus 9.1 ± 0.3 (p = .015) 2 weeks and 1 month after the intervention, respectively. The total insomnia severity scores in the two groups of intervention and placebo were 9.0 ± 0.3 versus 12.1 ± 0.3 (p < .001) and 5.6 ± 0.5 versus 11.0 ± 0.5 (p < .001) 2 weeks and 1 month after the intervention, respectively. Consumption of O. basilicum capsules improved sleep quality and insomnia in menopausal women. This study was approved (code IR.MUMS.NURSE.REC.1398.070) by the Ethic committee of Mashhad University of Medical Sciences and registered at the Iranian Registry of Clinical Trials, with the No. IRCT20200104046001N1 in January 2020., (© 2023 John Wiley & Sons Ltd.)

Background: Glyphosate-based herbicides have been one of the most intensively used pollutants worldwide and food products containing glyphosate are an essential component of human and animal diet. The aim of present study was to determine the effect of glyphosate intoxication on the neurochemical properties of the enteric nervous system (ENS) neurons located in the wall of the porcine duodenum., Methods: Fifteen sexually immature gilts divided into 3 groups were used: control-animals receiving empty gelatin capsules; G1-animals receiving a low dose of glyphosate-corresponding to the theoretical maximum daily intake (TMDI) - 0.05 mg/kg bw/day; G2-animals receiving a higher dose of glyphosate-corresponding to the acceptable daily intake (ADI)-0.5 mg/kg/day in gelatin capsules orally for 28 days. After this time, the animals were euthanized and small intestine samples were collected. Frozen sections were then subjected to the procedure of double immunofluorescent staining., Key Results: Glyphosate supplementation led to alterations in the neurochemical code of the ENS neurons in the porcine duodenum. Generally, increased population of neurons immunoreactive to PACAP, CGRP, CART, nNOS, and a decreased number of VAChT-like immunoreactive neurons were noted., Conclusions and Inferences: It may be a first preclinical symptom of digestive tract dysfunction in the course of glyphosate intoxication and further studies are needed to assess the toxicity and risks of glyphosate to humans., (© 2022 John Wiley & Sons Ltd.)

Introduction: Little is known about the protective effects of butylphthalide on cerebral ischemia-reperfusion injury. This study aims to investigate the impact on the second mitochondrial-derived activator of Caspases (Smac) and X-linked inhibitor of apoptosis protein (XIAP) expression in the ischemic semidark area using a rat model of carotid artery stenosis., Methods: Thirty Sprague-Dawley rats were randomly divided into the sham-operated group, carotid stenosis model controls, low-dose (20 mg/kg), medium-dose (40 mg/kg), and high-dose (80 mg/kg) butylphthalide groups. The neurological function was scored by the balance beam test (BBT). The morphological changes of brain tissue were detected by Hematoxylin-eosin (HE) staining, with apoptosis detected by Terminal Deoxynucleotidyl Transferase mediated dUTP Nick-End Labeling (TUNEL) staining. Smac and XIAP protein expression were detected by immunohistochemistry (IHC). The expressions of Smac and XIAP mRNA were detected by real-time quantitative polymerase chain reaction (RT-qPCR)., Results: HE showed that neuronal loss, nuclear consolidation, and vacuolar degeneration were significantly reduced in the medium and high-dose butylphthalide groups compared with the model controls. The BBT scores and apoptotic index were significantly lower in the medium and high doses of butylphthalide compared with the model controls. RT-qPCR and IHC showed that Smac, XIAP mRNA and protein expressions in the ischemic hemispheric region were significantly reduced in low, medium, and high doses of butylphthalide compared with the model controls (P < 0.05), showing some concentration effect., Conclusions: Butylphthalide can significantly reduce Smac and XIAP mRNA and protein expression, inhibit neuronal apoptosis induced by ischemia-reperfusion injury in rats with carotid stenosis, and exert neuroprotective effects., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In response to current trends in the modification of guided bone regeneration (GBR) materials, we aimed to build upon our previous studies on epigallocatechin-3-gallate (EGCG) by immersing a commonly used bone graft primarily composed of hydroxyapatite (HA) in EGCG solution, expecting to obtain superior bone material integration after implantation. Bone grafts are commonly used for bone repair, in which the bone extracellular matrix is stimulated to promote osteogenesis. However, due to its profibrosis effect, this osteoconductive material commonly exhibits implant failure. In addition to providing a basic release profile of EGCG-modified bone graft (E-HA) to clarify the relationship between this material and the environment, we have examined the integration effect via subcutaneous implantation experiments. In this manner, we have assessed the aggregation of proinflammatory macrophages, the formation of fibrous capsules, and an enhanced cell viability observed in cultured RAW 264.7 cells. Among these results, we focus on proinflammatory macrophages due to their close relationship with fibrosis, which is the most important process in the immune response. Immunofluorescent staining results showed that E-HA substantially compromised the formation of fibrous capsules in hematoxylin-eosin-stained sections, which exhibited less proinflammatory macrophage recruitment; meanwhile, the cell viability was improved. This work lays the foundation for future studies on GBR., Competing Interests: There are no conflicts of interest related to this manuscript., (Copyright © 2023 Dengbo Yao et al.)

Alginate-based microcapsule has becoming a promising carrier for probiotic encapsulation due to the improved stress resistant ability. Besides the physical protection of microcapsules, bacterial quorum sensing (QS) is another prominent factor affecting microbial stress resistance in microcapsules. In the present study, Vibrio harveyi cells were entrapped and proliferated into cell aggregates in alginate-based microcapsules. The microenvironment composed of cells and biomacromolecules was regulated by the diameter, alginate concentration and core state of microcapsule. Then the effect of microenvironment on bacterial QS capacity was investigated, including bioluminescence, autoinducers (AIs) production and QS related genes expression. The highest diameter of 1200 μm and highest alginate concentration of 2.0 % w/v under the investigation range presented strongest QS capacity, and the maintenance of hydrogel core could enhance bacterial QS. Moreover, the mechanism analysis revealed that the formed biofilm on the surface of cell aggregates hampered the outward transfer of AIs, and the local AIs inside the cell aggregates induced stronger bacteria QS by close-range interaction. As a whole, these findings are helpful to guide the technological development and optimization of microencapsulated probiotics with stronger stress resistance, and the potential application in food, dairy, wastewater treatment and biosensor., Competing Interests: Declaration of competing interest On behalf of all authors of the manuscript entitled with ‘Enhanced quorum sensing capacity via regulating microenvironment to facilitate stress resistance of probiotic in alginate-based microcapsules’, I would hereby disclose that there is no any financial or non-financial assistance provided by a third party for the reported work., (Copyright © 2022. Published by Elsevier B.V.)

Intracerebral transplantation of neural stem cells (NSCs) for ischemic stroke treatment has been demonstrated to be inefficient, with only &lt;5% of delivered cells being retained. Microcapsules may be a good carrier for NSC delivery; however, the current microcapsules do not fully meet the demands for cell survival after transplantation. In the present study, we designed a strategy for the encapsulation of NSCs in a novel lipid-alginate (L-A) microcapsule based on a two-step method. The protective effect of a L-A microcapsule on oxygen-glucose deprivation (OGD) was investigated by using the CCK8 test, the LDH release test, and flow cytometry. Mechanisms underlying the prosurvival effect were investigated by detecting autophagy markers like P62, LC3-I, and LC3-II, and autophagy flux analysis was also performed. Lastly, the ability of the L-A microcapsule to support NSCs delivery for ischemic stroke was investigated in the middle cerebral artery occlusion (MCAO) model. We found that L-A microcapsules exerted a good protective effect against OGD compared with control and alginate microcapsules. The L-A microcapsules were found to promote cell survival by not only providing a "physical" barrier but also altering autophagy markers like P62 and LC3-II, which enhanced autophagy flux. This novel microcapsule was confirmed to be suitable for NSC delivery in vivo, which alleviated transplanted NSC apoptosis, reduced the infarct volume, decreased brain edema, improved neurological deficit scores, and lastly, improved survival rate. The findings of this study may provide a new method for stem cell delivery, raising the prospect that intracerebral cell transplantation may be used to treat, for instance, ischemic stroke, traumatic brain injury, and so on.

Maintaining the stemness of the transplanted stem cell spheroids in an inflammatory microenvironment is challenging but important in regenerative medicine. Direct delivery of stem cells to repair periodontal defects may yield suboptimal effects due to the complexity of the periodontal inflammatory environment. Herein, stem cell spheroid is encapsulated by interfacial assembly of metal-phenolic network (MPN) nanofilm to form a stem cell microsphere capsule. Specifically, periodontal ligament stem cells (PDLSCs) spheroid was coated with Fe III /tannic acid coordination network to obtain spheroid@[Fe III -TA] microcapsules. The formed biodegradable MPN biointerface acted as a cytoprotective barrier and exhibited antioxidative, antibacterial and anti-inflammatory activities, effectively remodeling the inflammatory microenvironment and maintaining the stemness of PDLSCs. The stem cell microencapsulation proposed in this study can be applied to multiple stem cells with various functional metal ion/polyphenol coordination, providing a simple yet efficient delivery strategy for stem cell stemness maintenance in an inflammatory environment toward a better therapeutic outcome., (© 2022. The Author(s).)

Microcapsules serve as a feasible formulation to load phenolic substances such as salicylic acid, a natural and safe antimicrobial agent. However, the antibacterial efficacy of salicylic acid microcapsules (SAMs) remains to be elucidated. Here, salicylic acid/β-cyclodextrin inclusion microcapsules were subjected to systematic antibacterial assays and preliminary antibacterial mechanism tests using Escherichia coli and Staphylococcus aureus as target organisms. It was found that the core-shell rhomboid-shaped SAMs had a smooth surface. SAMs exhibited a minimum inhibitory concentration (MIC) and a minimum bactericidal concentration (MBC) of 4 mg/mL against both bacteria. In the growth inhibition assay, 1/4 × MIC, 1/2 × MIC, and 1 × MIC of SAMs effectively retarded bacterial growth, and this effect was more prominent with the rise in the level of SAMs. Practically, SAMs possessed a rapid bactericidal effect at the 1 × MIC level with a reduction of more than 99.9% bacterial population within 10 min. A pronounced sterilization activity against E. coli and S. aureus was also observed when SAMs were embedded into hand sanitizers as antimicrobial agents. Moreover, exposure of both bacteria to SAMs resulted in the leakage of intracellular alkaline phosphatases and macromolecular substances (nucleic acids and proteins), which indicated the disruption of bacterial cell walls and cell membranes. In conclusion, SAMs were able to inactivate E. coli and S. aureus both in vitro and in situ , highlighting the promising utilization of this formulation for antimicrobial purposes in the area of food safety and public health.

A retrospective cohort study to explore the clinical efficacy and safety evaluation of calcitriol combined with bisphosphonates in the therapy of postmenopausal osteoporosis is conducted. The postmenopausal osteoporosis sufferers admitted to our hospital from January 2020 to June 2021 are retrospectively collected and divided into a contrast set and a study set, with 60 cases in each set. For the contrast set, all sufferers are treated with bisphosphonates. For the study set, on the basis of the therapy drugs in the contrast set, they are treated with calcitriol capsules. Firstly, the curative effects, bone mineral density standards, and bone metabolism standards of the two sets are contrasted; then, the lumbar spine bone mineral density, VAS score, and quality of life between the two sets of sufferers before therapy and 1 year after therapy are contrasted, and the correlation between bone mineral density and VAS and quality of life of the sufferers is analyzed. Lastly, the readmission situation between the two sets at one year is contrasted. The experimental results show that for postmenopausal women with osteoporosis, calcitriol combined with bisphosphonate therapy can notoriously enhance the clinical therapy effect of sufferers, with low adverse reactions, and can effectively enhance the bone mineral density and bone density of sufferers., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Weibing Jing et al.)

Posterior capsular opacification (PCO) can cause postoperative visual loss after cataract surgery. Residual human lens epithelial cell (HLEC) proliferation, migration, epithelial-mesenchymal transition (EMT) and synthesis of extracellular matrix (ECM) are the entitative reasons for PCO. Low expression of Ral-binding protein 1-associated Eps domain-containing 2 (REPS2) and high levels of basic fibroblast growth factor (b-FGF) were observed in the lens and postoperative aqueous humor of cataract patients. REPS2 was identified as a negative regulator in growth factor signaling; however, its function in HLECs is unknown. This was first investigated in the present study by evaluating REPS2 expression in anterior lens capsules from cataract patients, a mouse cataract model, and HLE-b3 cells. The biological function of REPS2 in HLE-B3 cells was assessed by REPS2 silencing and Cell Counting Kit 8, wound healing, Transwell migration, F-actin staining, G-protein pulldown and western blot assays. In the present study, REPS2 was significantly downregulated in human and mouse cataract capsules and H 2 O 2 -treated HLE-B3 cells. REPS2 knockdown increased fibronectin, type I collagen, and α-smooth muscle actin expression levels and stimulated HLECs proliferation and migration; these effects were enhanced by FGF treatment and accompanied with focal adhesion kinase (FAK) phosphorylation, cell division cycle 42 (Cdc42) activation, focal adhesion protein upregulation, and F-actin cytoskeleton reorganization. However, treatment with the FAK inhibitor PF573228 abolished these effects. Thus, REPS2 downregulation in cataract HLECs induces their proliferation and facilitates FGF-induced ECM synthesis, EMT, cell adhesion and migration by activating FAK/Cdc42 signaling, which may underlie PCO pathogenesis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Antithrombotic therapy is confronted with short half-lives of thrombolytic agents and high bleeding risks. Challenges remain in the development of drug delivery systems for thorough destruction of thrombi and timely restoration of blood flow while minimizing side effects. Herein, polydopamine capsule-like micromotors with urokinase (uPA) loadings and Arg-Gly-Asp (RGD) grafts (r-u@PCM) were constructed using rod-shaped bacteria as the template, and one single opening was created on each capsule through bacterial ghost (BG) formation. Glucose oxidase and catalase were encapsulated in the large cavity of microcapsules, and their successive oxidation of glucose produced O 2 bubbles, which ejected out through the single opening to propel the motion of r-u@PCM. In vitro targeting testing of r-u@PCM shows significant higher accumulations on the activated platelets than those without RGD grafts (u@PCM, 7 folds) or without enzyme loadings (r-u@PC, 11 folds). Compared with the major distribution of r-u@PC on the clot surface, r-u@PCM efficiently penetrates into clots with dense fibrin networks, and near-infrared (NIR) irradiation (r-u@PCM/NIR) promotes thrombus infiltration through increasing uPA release and thermolysis of the networks. Pharmacokinetic study shows that the loading of uPA in r-u@PCM extends the terminal half-life from 24 min to 5.5 h and the bioavailability increased 13 times. In a hindlimb venous thrombosis model, r-u@PCM/NIR treatment promotes uPA accumulations in thrombi and disrupts all the thrombi after 8 h with a full recovery of blood flows. Effective thrombolysis is also achieved even after reducing the uPA dose 5 times. Thus, this is the first attempt to fabricate rod-shaped microcapsule motors through a biologically derived method, including bacterial templating and BG formation-induced opening generation. r-u@PCM/NIR treatment promotes thrombolysis through the photothermal effect, self-propelled infiltration into thrombi, and accelerated local release of uPA, providing a prerequisite for reducing uPA dose and bleeding side effects.

Inflammatory reaction and neuronal apoptosis are the major pathophysiological mechanisms involved in cerebral ischemia-reperfusion injury (CI/RI). It has been reported that Zhongfeng Capsules (ZFCs), which contain Panax notoginseng, Hirudo, Red ginseng, Eupolyphaga sinensis, Pangolin scales, Rhubarb, and Radix Salvia miltiorrhizae, have a definite therapeutic effect on CI/RI. However, the specific molecular mechanisms of ZFCs are unclear. In this study, the effects of ZFCs on middle cerebral artery occlusion were investigated in rats. Our results showed that neurological impairment and neuronal apoptosis were alleviated in ZFC-treated rats. Additionally, infarct volume and cerebral edema decreased and there was an improvement in histopathological features. Furthermore, the expression levels of IL-1β, IL-6, and TNF-α were downregulated in ZFC-treated rats. TLR 4, NF-κB, Bax, and Caspase-3 expression also tended to decrease, whereas the expression of Bcl-2, p-PI3K, p-Akt, and I-κBα increased. The results indicate that the ZFCs effectively protected the rats against CI/RI possibly via the TLR4/NF-κB signaling pathway. Additionally, the formulation regulated the transcriptional activity of NF-κB, secretion of downstream inflammatory factors, and the expression of Bcl-2-Bax proteins in the PI3K/Akt pathway. Our findings suggest that ZFCs suppress neuronal apoptosis and inflammatory reaction via the PI3K/Akt and TLR4/NF-κB signaling pathways, respectively. Moreover, activation of the PI3K/Akt pathway may result in the inhibition of proinflammatory cytokine secretion, which may be another mechanism by which ZFCs alleviate CI/RI., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Patients with heart failure with preserved ejection fraction (HFpEF) have few pharmacologic therapies, and it is not known if supplementing with ubiquinol and/or d-ribose could improve outcomes. The overall objective of this study was to determine if ubiquinol and/or d-ribose would reduce the symptoms and improve cardiac performance in patients with HFpEF. This was a phase 2 randomized, double-blind, placebo-controlled trial of 216 patients with HFpEF who were ≥ 50 years old with a left ventricular ejection fraction (EF) ≥ 50%. A total of 4 study groups received various supplements over 12 weeks: Group 1 received placebo ubiquinol capsules and d-ribose powder, Group 2 received ubiquinol capsules (600 mg/d) and placebo d-ribose powder, Group 3 received placebo ubiquinol capsules with d-ribose powder (15 g/d), and Group 4 received ubiquinol capsules and d-ribose powder. There were 7 outcome measures for this study: Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score, level of vigor using a subscale from the Profile of Mood States, EF, the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity (septal E/e' ratio), B-type natriuretic peptides, lactate/adenosine triphosphate ratio, and the 6-minute walk test. Treatment with ubiquinol and/or d-ribose significantly improved the KCCQ clinical summary score (17.30 to 25.82 points), vigor score (7.65 to 8.15 points), and EF (7.08% to 8.03%) and reduced B-type natriuretic peptides (-72.02 to -47.51) and lactate/adenosine triphosphate ratio (-4.32 to -3.35 × 10 -4 ). There were no significant increases in the septal E/e' or the 6-minute walk test. In conclusion, ubiquinol and d-ribose reduced the symptoms of HFpEF and increased the EF. These findings support the use of these supplements in addition to standard therapeutic treatments for patients with HFpEF., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Potato tubers tend to sprout during long-term storage, resulting in quality deterioration and shortened shelf life. Restrictions on the use of chlorpropham, the major potato sprout suppressant, have led to a need to seek alternative methods. In this study, the effects of methyl jasmonate (MeJA) solutions and MeJA microcapsules on sprouting and other key quality attributes of the potato tuber were investigated. The results showed that the MeJA solution was most effective at 300 μmol L -1 according to TOPSIS analysis. To prepare MeJA microcapsules, the optimal formulation is with 0.04% emulsifier, 2.5% sodium alginate, 0.5% chitosan and 3% CaCl 2 . Compared to 300 μmol L -1 MeJA solution, MeJA microcapsules consumed a lower dose of MeJA but demonstrated a better retaining effect on the overall quality attributes of potato tubers. MeJA microcapsules are promising agents for the preservation of postharvest potato tubers.

The common and frequent disease, ulcerative colitis (UC), causes serious physical and mental distress to patients. M2 macrophages have proven to play a role in anti-inflammation, which is a new potential target for UC therapy. In this study, we designed a safe and macrophages-targeting oral drug delivery system. Natural products, berberine (BBR), and Epigallocatechin Gallate (EGCG) with anti-inflammatory activity were assembled and encapsulated into yeast microcapsule (YM), generating therapeutic system BBR/MPN@YM. BBR and EGCG exhibited synergistic effects against UC through the effect of antioxidation. Through the interaction between β-1,3-d-glucan on the surface of YM and dectin-1 receptors on macrophages, BBR/MPN@YM could be effectively transported to inflammation parts and internalized into macrophages, avoiding gastric degradation. In the in vivo UC mouse model, BBR/MPN@YM could transform M1 macrophages into anti-inflammatory M2 macrophages, thus exerting specific anti-inflammatory effects. Therefore, this BBR/MPN@YM targeted oral drug delivery system provided a new macrophages-targeting strategy for the clinical treatment of UC.

Objective: This study aimed to investigate the effect of aerobic exercise combined with glucosamine (OTL) on the apoptosis of chondrocytes of rabbit knee osteoarthritis (KOA) by affecting the expression of TRPV5., Methods: After the KOA white rabbit model was established, aerobic training and OTL treatment were performed, then the model joints were evaluated by Mankin, HE staining was used to observe the pathological changes of articular cartilage, TUNEL and immunohistochemistry were used to detect chondrocyte apoptosis. Knee chondrocytes were isolated and identified by Alcian Blue and type II collagen fiber staining. The cells were treated with iodoacetic acid (MIA) to simulate osteoarthritis in vitro, and then the effect of TRPV5 on apoptosis was detected by flow cytometry, in addition, apoptosis-related proteins and TRPV5 were detected by western blotting and qRT-PCR., Results: Both aerobic exercise and OTL treatment could significantly reduce the Mankin score of KOA model, and could effectively inhibit chondrocyte apoptosis in the KOA model, and inhibit the expression of caspase 3 and caspase 9 in the KOA model. TRPV5 expression was significantly increased in the model, while both aerobic exercise and OTL could reverse its expression. The low-expression of TRPV5 significantly reversed the role of MIA in promoting apoptosis and apoptosis-related proteins of knee chondrocytes, while overexpressing TRPV5 promoted MIA-induced apoptosis and apoptosis-related proteins., Conclusion: Aerobic exercise combined with glucosamine hydrochloride capsules inhibited the apoptosis of chondrocytes in rabbit KOA by affecting the expression of TRPV5., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: The study is aimed at exploring the effect of the controlled release of the glial-derived neurotrophic factor (GDNF) on nerve regeneration., Methods: The PLGA/chitosan composite nerve conduit was used to bridge the dissected trunk of the rat facial nerve. GDNF microcapsules were loaded into the nerve conduit. Nine weeks after surgery, the facial nerve zygomatic and buccal branches were labeled with fluorescent indicators. The incorrectly grown facial neurons were reversed and counted. The facial nerve functional recovery was assessed by measuring the maximum evoked potential., Results: The nerve conduit was filled with different regenerating factors, such as the GDNF, GDNF microcapsules, or saline (control). The number of incorrectly regenerated neurons was lower with the nerve conduits filled with GDNF microcapsules than with those supplied with just the GDNF. However, neither the GDNF nor GDNF microcapsules affected the number of regenerated neurons. The functional recovery of the facial nerve was the best, with the nerve conduit filled with GDNF microcapsules closest to the healthy uncut facial nerve., Conclusion: The stable slow-release GNDF microcapsule inside the biodegradable nerve conduit can reduce the extent of incorrect growth of the facial nerve neuron when bridging the dissected rat facial nerve trunk. The technique has a good effect on functional nerve recovery., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Siwen Xia et al.)

Female pediatric cancer survivors often develop Premature Ovarian Insufficiency (POI) owing to gonadotoxic effects of anticancer treatments. Here we investigate the use of a cell-based therapy consisting of human ovarian cortex encapsulated in a poly-ethylene glycol (PEG)-based hydrogel that replicates the physiological cyclic and pulsatile hormonal patterns of healthy reproductive-aged women. Human ovarian tissue from four donors was analyzed for follicle density, with averages ranging between 360 and 4414 follicles/mm 3 . Follicles in the encapsulated and implanted cryopreserved human ovarian tissues survived up to three months, with average follicle densities ranging between 2 and 89 follicles/mm 3 at retrieval. We conclude that encapsulation of human ovarian cortex in PEG-based hydrogels did not decrease follicle survival after implantation in mice and was similar to non-encapsulated grafts. Furthermore, this approach offers the means to replace the endocrine function of the ovary tissue in patients with POI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor YF declared a past collaboration with the author AS., (Copyright © 2022 Brunette, Kinnear, Hashim, Flanagan, Day, Cascalho, Padmanabhan and Shikanov.)

Cardiovascular diseases (CVD) are the leading causes of mortality worldwide. Flow-mediated dilation (FMD) is a marker of vascular function. Beneficial cardiometabolic effects of Nigella sativa (N. sativa) have been observed. We evaluated the effect of N. sativa oil on FMD, plasma nitrite, and nitrate (NOx) as nitric oxide (NO) metabolites, and inflammatory markers in subjects with CVD risk factors. Fifty participants were randomly assigned to either the N. sativa (two capsules of 500 mg N. sativa oil) or the placebo group (two capsules of 500 mg mineral oil), for 2 months. The brachial FMD, plasma NOx, vascular cellular adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) were measured. FMD and plasma NOx levels was significantly increased in the N. sativa group compared to the placebo group (changes: 2.97 ± 2.11% vs. 0.71 ± 3.19%, p < 0.001 for FMD and 4.73 ± 7.25 μmol/L vs. 0.99 ± 5.37 μmol/L, p = 0.036 for plasma NOx). However, there was no significant difference in ICAM-1 and VCAM-1 levels between groups. Therefore, N. sativa oil improves vascular NO and FMD in subjects with cardiovascular risk factors. However, more studies are warranted to confirm the beneficial impacts of the N. sativa oil on vascular inflammation., (© 2022 John Wiley & Sons, Ltd.)

Introduction. Atherosclerosis is a chronic disorder in which plaque builds up in the arteries and is associated with several cardiovascular and cerebrovascular diseases such as coronary artery disease, cerebral infarction and cerebral haemorrhage. Therefore, there is an urgent need to discover new medications to treat or prevent atherosclerosis. Hypothesis/Gap Statement. The active components of Guanxin Xiaoban capsules may have an effect on the gut microbiome of patients with atherosclerosis and have a role in their therapeutic targets. Aim. The aim of this study was to identify genes and pathways targeted by active ingredients in Guanxin Xiaoban capsules for the treatment of atherosclerosis based on network pharmacology and analysis of changes to the gut microbiome. Methods. Mice were treated with Guanxin Xiaoban capsules. The 16S rDNA genome sequence of all microorganisms from each group of faecal samples was used to evaluate potential structural changes in the gut microbiota after treatment with Guanxin Xiaoban capsules. Western blotting and real-time quantitative PCR were used to detect gene targets in aortic and liver tissues. Haematoxylin and eosin staining was used to observe improvements in mouse arterial plaques. Results. The gut microbiota of atherosclerotic mice is disturbed. After Guanxin Xiaoban treatment, the abundance of bacteria in the mice improved, with an increase in the proportion of Akkermansia and a significant decrease in the proportion of Faecalibaculum . The main ingredients of Guanxin Xiaoban capsules are calycosin, liquiritin, ferulic acid, ammonium glycyrrhizate, aloe emodin, rhein and emodin. The core genes of this network were determined to be glutathione S -transferase mu 1 (GSTM1), vascular endothelial growth factor A (VEGFA) and cyclin-dependent kinase inhibitor 1A (CDKN1A). The compound-target gene network revealed an interaction between multiple components and targets and contributed to a better understanding of the potential therapeutic effects of the capsules on atherosclerosis. In addition, expression of the AGE-receptor for the AGE (RAGE) pathway was significantly inhibited and the mice showed signs of arterial plaque reduction. Guanxin Xiaoban capsules may improve atherosclerosis and reduce the plaque area by inhibiting the AGE-RAGE signalling pathway to delay the development of atherosclerosis. This mechanism appears to involve changes in the gut microbiota. Therefore, Guanxin Xiaoban capsules have potential value as a treatment for atherosclerosis.

Manipulation of gut microbiota by bacterial metabolites has shown protective effects against colitis; while the efficacy is strictly limited by the poor oral delivery efficiency and single drug usage. Here, a novel prebiotics and postbiotics synergistic delivery microcapsule composed of indole-3-propionic acid (IPA) postbiotic and three prebiotics including alginate sodium, resistant starch (RS), and chitosan via microfluidic electrospray for preventing and treating colitis are proposed. It is found that oral administration of IPA microcapsules (IPA@MC) to mice can exert significant protective effects to colitis, suggesting the therapeutic synergy between prebiotics and postbiotics. Furthermore, the mechanism of the IPA@MC is revealed in modulating the gut microbiota, that is by significantly increasing the overall richness and abundance of short-chain fatty acids (SCFA) producing bacteria such as Faecalibacterium and Roseburia. These results indicate that the prebiotics and postbiotics synergistic delivery microcapsules are ideal candidates for treating colitis., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: Gastrointestinal enteroendocrine cells express chemosensory bitter taste receptors that may play an important role in regulating energy intake (EI) and gut function., Objectives: To determine the effect of a bitter hop extract (Humulus lupulus L.) on acute EI, appetite, and hormonal responses., Methods: Nineteen healthy-weight men completed a randomized 3-treatment, double-blind, crossover study with a 1-wk washout between treatments. Treatments comprised either placebo or 500 mg of hop extract administered in delayed-release capsules (duodenal) at 11:00 h or quick-release capsules (gastric) at 11:30 h. Ad libitum EI was recorded at the lunch (12:00 h) and afternoon snack (14:00 h), with blood samples taken and subjective ratings of appetite, gastrointestinal (GI) discomfort, vitality, meal palatability, and mood assessed throughout the day., Results: Total ad libitum EI was reduced following both the gastric (4473 kJ; 95% CI: 3811, 5134; P = 0.006) and duodenal (4439 kJ; 95% CI: 3777, 5102; P = 0.004) hop treatments compared with the placebo (5383 kJ; 95% CI: 4722, 6045). Gastric and duodenal treatments stimulated prelunch ghrelin secretion and postprandial cholecystokinin, glucagon-like peptide 1, and peptide YY responses compared with placebo. In contrast, postprandial insulin, glucose-dependent insulinotropic peptide, and pancreatic polypeptide responses were reduced in gastric and duodenal treatments without affecting glycemia. In addition, gastric and duodenal treatments produced small but significant increases in subjective measures of GI discomfort (e.g., nausea, bloating, abdominal discomfort) with mild to severe adverse GI symptoms reported in the gastric treatment only. However, no significant treatment effects were observed for any subjective measures of appetite or meal palatability., Conclusions: Both gastric and duodenal delivery of a hop extract modulates the release of hormones involved in appetite and glycemic regulation, providing a potential "bitter brake" on EI in healthy-weight men., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objective: The clinical efficacy of Xianling Gubao capsule (XLGB) and its combination therapy in the treatment of postmenopausal osteoporosis (PMOP) was systematically evaluated by frequency-based network meta-analysis., Methods: We searched the China National Knowledge Infrastructure (CNKI), Wanfang, SinoMed, PubMed, Embase and Cochrane Library databases to identify clinical trials of XLGB for the treatment of PMOP from the establishment of each database to November 22, 2021. The quality of the included studies was evaluated by using the risk of bias assessment tool version 2.0 (Rob 2.0) recommended by Cochrane. Stata 14.0 was applied for statistical analysis of the data, and the surface under the cumulative ranking curve (SUCRA) was used to rank the intervention measures of each outcome index., Results: This study included 22 clinical trials (including 19 RCTs and 3 non-RCTs) involving 12 drug therapies. According to the results of the network meta-analysis and SUCRA, the best three interventions for improving lumbar bone mineral density (BMD) are XLGB+BP+calcium (83.7%), XLGB+BP (68.5.7%) and XLGB+VD (67.1%). XLGB+calcium was the best combination regimen for improving femoral neck BMD and increasing bone Gla protein (BGP) and alkaline phosphatase (ALP) contents in serum. The SUCRA values of XLGB+calcium for improving the three outcome indicators were 68.0%, 59.5% and 82.1%, respectively., Conclusions: The results of this network meta-analysis show that combined application of XLGB can effectively improve BMD and serum BGP and ALP compared to calcium alone, VD or BP. In the future, multicenter, large-sample and double-blind clinical RCTs should be carried out to supplement and verify the results of this study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Zhao, Xu, Xiao, Feng, Li and Zeng.)

In nature, individual cells are compartmentalized by a membrane that protects the cellular elements from the surrounding environment while simultaneously equipped with an antioxidant defense system to alleviate the oxidative stress resulting from light, oxygen, moisture, and temperature. However, this mechanism has not been realized in cellular mimics to effectively encapsulate and retain highly reactive antioxidants. Here, we report cell-inspired hydrogel microcapsules with an interstitial oil layer prepared by utilizing triple emulsion drops as templates to achieve enhanced retention of antioxidants. We employ ionic gelation for the hydrogel shell to prevent exposure of the encapsulated antioxidants to free radicals typically generated during photopolymerization. The interstitial oil layer in the microcapsule serves as an stimulus-responsive diffusion barrier, enabling efficient encapsulation and retention of antioxidants by providing an adequate pH microenvironment until osmotic pressure is applied to release the cargo on-demand. Moreover, addition of a lipophilic reducing agent in the oil layer induces a complementary reaction with the antioxidant, similar to the nonenzymatic antioxidant defense system in cells, leading to enhanced retention of the antioxidant activity. Furthermore, we show the complete recovery and even further enhancement in antioxidant activity by lowering the storage temperature, which decreases the oxidation rate while retaining the complementary reaction with the lipophilic reducing agent.

Probiotics are incorporated into food products because of numerous favorable effects on human health. The viability of probiotics is often affected by unfavorable interference during processing. The encapsulation can provide protection to probiotics during mechanical processing, storage, and gastrointestinal digestion. This study aimed to evaluate the protective effect of whey protein isolate (WPI) and dextran (DX) conjugates for Lactobacillus plantarum. The WPI-DX conjugate was prepared by Maillard-based glycation and confirmed by gel electrophoresis. Extending the heating time from 1 to 5 h decreased the content of tryptophan residues and increased the amide I and amide II bands. The enhanced protective ability of Maillard reaction products (MRPs) for L. plantarum was observed under conditions of stress (pH, heat, and salt) and in vitro digestion. In situ viability tests showed that encapsulation improved the survival of bacteria in kefir during 15 days of storage at 4 °C. Overall, our results provide valuable information for the development of functional probiotic food products., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Directed neural differentiation of embryonic stem cells (ESCs) has been studied extensively to improve the treatment of neurodegenerative disorders. This can be done through stromal-cell derived inducing activity (SDIA), by culturing ESCs directly on top of a layer of feeder stromal cells. However, the stem cells usually become mixed with the feeder cells during the differentiation process, making it difficult to obtain a pure population of the differentiated cells for further use. To address this issue, a non-planar microfluidic device is used here to encapsulate murine ESCs (mESCs) in the 3D liquid core of microcapsules with an alginate hydrogel shell of different sizes for early neural differentiation through SDIA, by culturing mESC-laden microcapsules over a feeder layer of PA6 cells. Furthermore, the alginate hydrogel shell of the microcapsules is modified via oxidation or RGD peptide conjugation to examine the mechanical and chemical effects on neural differentiation of the encapsulated mESC aggregates. A higher expression of Nestin is observed in the aggregates encapsulated in small (∼300 μm) microcapsules and cultured over the PA6 cell feeder layer. Furthermore, the modification of the alginate with RGD facilitates early neurite extension within the microcapsules. This study demonstrates that the presence of the RGD peptide, the SDIA effect of the PA6 cells, and the absence of leukemia inhibition factor from the medium can lead to the early differentiation of mESCs with extensive neurites within the 3D microenvironment of the small microcapsules. This is the first study to investigate the effects of cell adhesion and degradation of the encapsulation materials for directed neural differentiation of mESCs. The simple modifications (i.e., oxidation and RGD incorporation) of the miniaturized 3D environment for improved early neural differentiation of mESCs may potentially enhance further downstream differentiation of the mESCs into more specialized neurons for therapeutic use and drug screening., (© 2021 S. Karger AG, Basel.)

Lenvatinib (LT) is gradually replacing sorafenib as an alternative targeted drug against advanced hepatocellular carcinoma (HCC). However, the anticancer effects of LT are still limited because of its low cytotoxicity, multidrug resistance (MDR), and tumor relapse. Herein, we constructed a smart biophotonic nanoplatform to overcome the barriers preventing high performance. LT and copper sulfide nanocrystals (Cu 2- x S NCs) with excellent photothermal properties in the near-infrared-II (NIR-II) zone were co-encapsulated in poly(D,L-lactide- co -glycolide) (PLGA) through nanoprecipitation. Both in vitro and in vivo evaluations demonstrated that Cu 2- x S NCs enhanced the anticancer efficacy of LT, without recurrence. In addition, the presence of copper ions could allow glutathione (GHS) to be consumed and oxygen to be produced, likely suppressing the expression of P-glycoprotein (P-gp) and overcoming the issue of MDR relating to LT. More importantly, synergistic chemo-photothermal therapy with LT and Cu 2- x S NCs was more effective than any single therapy or theoretical combination. This nanoplatform is promising for advancing future LT-based treatment strategies for HCC therapy.

Tuberculosis (TB) is an infectious disease that causes a great number of deaths in the world (1.5 million people per year). This disease is currently treated by administering high doses of various oral anti-TB drugs for prolonged periods (up to 2 years). While this regimen is normally effective when taken as prescribed, many people with TB experience difficulties in complying with their medication schedule. Furthermore, the oral administration of standard anti-TB drugs causes severe side effects and widespread resistances. Recently, we proposed an original platform for pulmonary TB treatment consisting of mannitol microspheres (Ma MS) containing iron (III) trimesate metal-organic framework (MOF) MIL-100 nanoparticles (NPs). In the present work, we loaded this system with the first-line anti-TB drug isoniazid (INH) and evaluated both the viability and safety of the drug vehicle components, as well as the cell internalization of the formulation in alveolar A549 cells. Results show that INH-loaded MOF (INH@MIL-100) NPs were efficiently microencapsulated in Ma MS, which displayed suitable aerodynamic characteristics for pulmonary administration and non-toxicity. MIL-100 and INH@MIL-100 NPs were efficiently internalized by A549 cells, mainly localized in the cytoplasm. In conclusion, the proposed micro-nanosystem is a good candidate for the pulmonary administration of anti-TB drugs.

Two ways to deliver ultrasmall gold nanoparticles and gold-bovine serum albumin (BSA) nanoclusters to the colon were developed. First, oral administration is possible by incorporation into gelatin capsules that were coated with an enteric polymer. These permit the transfer across the stomach whose acidic environment damages many drugs. The enteric coating dissolves due to the neutral pH of the colon and releases the capsule's cargo. Second, rectal administration is possible by incorporation into hard-fat suppositories that melt in the colon and then release the nanocarriers. The feasibility of the two concepts was demonstrated by in-vitro release studies and cell culture studies that showed the easy redispersibility after dissolution of the respective transport system. This clears a pathway for therapeutic applications of drug-loaded nanoparticles to address colon diseases, such as chronic inflammation and cancer.

We report the microencapsulation of oil soluble vitamins (A, D and E) using a one pot ultrasonic process and raw egg white proteins as a shell material. Green tea catechin/iron complex coating method was further developed to impart UV filtering property to the microcapsules in order to protect the encapsulated nutrients from photodegradation. The microcapsules showed antibacterial properties and long shelf-life. The encapsulated vitamins were protected from degradation upon heating, UV irradiation, simulated storage/transit and cooking processes. The in-vitro digestion study showed that functional vitamin D can be potentially released in the gastrointestinal tract improving vitamin D availability by more than 2-fold compared to the free vitamin. The vitamin D microcapsules were highly stable and maintained their microstructures once incorporated into staple food products. The low-cost egg white shell encapsulated vitamins can improve the nutritional value of staple food products to combat maternal and child malnutrition., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the protective effects of Naoxintong capsules ( NXT)on tumor necrosis factor-α (TNF-α) -induced senescence inendothelial cells and its mechanism., Methods: Human umbilical vascular endothelial cells (HUVECs) were treated with TNF-α ± NXT and assessed for silent information regulator 1 (SIRT1) expression and signaling. Cells were stained with beta-galactosidase to assess the levels of cellular senescence. SIRT1 was silenced through siRNA transfection., Results: TNF-α treatment led to the downregulation of SIRT1, resulting in forkhead box O1 (FoxO-1) acetylation, p53 acetylation and enhanced p21 expression. Following TNF-α treatment, higher SA β-Gal activity improved. TNF-α enhanced the migration of HUVECs and increased SIRT1 expression, both of which were attenuated by NXT treatment. The downstream targets of SIRT1 including FoxO-1/p53/p21 were also modulated, and HUVECs were protected from TNF-α-induced senescence. In contrast, the NXT-mediated protection was prevented by SIRT1 silencing., Conclusions: These findings suggest that sustained endothelial senescence can be induced by TNF-α stimulation via the SIRT1/FoxO-1/p53/p21 pathway. The protection of NXT against TNF- was partially mediated through its effects on SIRT1. This highlights the promise of NXT as a therapeutic for atherosclerosis.

Chronic neuropathic pain, particularly peripheral pain, is a cause of great concern for diabetic patients. Current treatments include numerous agents such as capsaicinoids, a known deterrent of neuropathic pain despite the inconvenience associated with local side effects. In this context, the current work aims to elucidate the potential mechanisms involved in cytotoxicity by capsaicin and proposes an efficient formulation of capsaicin in alginate microcapsules, which significantly reduces side effects from capsaicin topical administration. For this, human dermal fibroblast cells were treated with alginate-microencapsulated capsaicin extracts and screened for potential cytotoxic effects produced by the treatment. Cell viability and morphology were examined, as well as oxidative stress status and anti-inflammatory potential. Our results show that the alginate encapsulated formulation of capsaicin exerted lower cytotoxic effects on human dermal fibroblasts as measured by cell viability and reactive oxygen species (ROS) production. Furthermore, the expression profiles of inflammatory cytokines were significantly altered by the treatment as compared with the control culture.

Application of natural products as new green agrochemicals with low average lifetime, low concentration doses, and safety is both complex and expensive due to chemical modification required to obtain desirable physicochemical properties. Transport, aqueous solubility, and bioavailability are some of the properties that have been improved using functionalized metal-organic frameworks based on zinc for the encapsulation of bioherbicides ( ortho -disulfides). An in situ method has been applied to achieve encapsulation, which, in turn, led to an improvement in water solubility by more than 8 times after 2-hydroxypropyl-β-cyclodextrin HP-β-CD surface functionalization. High-resolution high-angle annular dark-field scanning transmission electron microscopy (HR HAADF-STEM) and integrated differential phase contrast (iDPC) imaging techniques were employed to verify the success of the encapsulation procedure and crystallinity of the sample. Inhibition studies on principal weeds that infect rice, corn, and potato crops gave results that exceed those obtained with the commercial herbicide Logran. This finding, along with a short synthesis period, i . e ., 2 h at 25 °C, make the product an example of a new generation of natural-product-based herbicides with direct applications in agriculture.

Antibiotic-resistant bacteria are a significant and growing threat to human health. Recently, two-dimensional (2D) nanomaterials have shown antimicrobial activity and have the potential to be used as new approaches to treating antibiotic resistant bacteria. In this Research Article, we exfoliate transition metal dichalcogenide (TMDC) nanosheets using synthetic single-stranded DNA (ssDNA) sequences, and demonstrate the broad-spectrum antibacterial activity of MoSe 2 encapsulated by the T 20 ssDNA sequence in eliminating several multidrug-resistant (MDR) bacteria. The MoSe 2 /T 20 is able to eradicate Gram-positive Escherichia coli and Gram-positive Staphylococcus aureus at much lower concentrations than graphene-based nanomaterials. Eradication of MDR strains of methicillin-resistant S. aureus (MRSA), Enterococcus faecalis , Pseudomonas aeruginosa , Klebsiella pneumoniae , and Acinetobacter baumannii are shown to occur at at 75 μg mL -1 concentration of MoSe 2 /T 20 , and E. coli at 150 μg mL -1 . Molecular dynamics simulations show that the thymine bases in the T 20 sequence lie flat on the MoSe 2 surface and can, thus, form a very good conformal coating and allow the MoSe 2 to act as a sharp nanoknife. Electron microscopy shows the MoSe 2 nanosheets cutting through the cell membranes, resulting in significant cellular damage and the formation of interior voids. Further assays show the change in membrane potential and reactive oxygen species (ROS) formation as mechanisms of antimicrobial activity of MoSe 2 /T 20 . The cellular death pathways are also examined by mRNA expression. This work shows that biocompatible TMDCs, specifically MoSe 2 /T 20 , is a potent antimicrobial agent against MDR bacteria and has potential for clinical settings.

Cancer is a major health issue concerning to all of us. Current treatment options are still limited due to not-selective action. Encapsulation is contemplated as an innovative approach to address systemic toxicity and tumor resistance caused by traditional therapies, while increasing encapsulated compounds bioavailability. The coating material of capsules strongly determines the success of the system. Since alginate has been proved non-toxic, biocompatible and biodegradable, it is considered a potential vehicle for therapeutic factors encapsulation. Besides, it has the particular ability to form hydrogels, which hold a high-water content and greatly resemble to natural soft tissues. The present review exposes the state-of-the-art and the most sophisticated alginate-based systems for cancer therapy and research. It begins with an overview of alginate hydrogels and the qualities that make them especially suitable for biomedical applications. In the following section, the application of alginate hydrogels as pioneering strategies for cancer treatment is described. Several examples of alginate-based delivery systems of therapeutic drugs, proteins and nucleic acids are provided. Significant emphasis is placed in both oral delivery systems and colorectal cancer therapy. Moreover, the role of alginate 3-D scaffolds for both cell culture and delivery is explained. Lastly, other applications of alginate-based hydrogels such as tumor biomarkers immunosensing and fluorescent surgical marker are included., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The microencapsulation is an ideal solution to overcome immune rejection without immunosuppressive treatment. Poor biocompatibility and small molecular antigens secreted from encapsulated islets induce fibrosis infiltration. Therefore, the aims of this study were to improve the biocompatibility of microcapsules by dexamethasone coating and to verify its effect after xenogeneic transplantation in a streptozotocin-induced diabetes mice., Methods: Dexamethasone 21-phosphate (Dexa) was dissolved in 1% chitosan and was cross-linked with the alginate microcapsule surface. Insulin secretion and viability assays were performed 14 days after microencapsulation. Dexa-containing chitosan-coated alginate (Dexa-chitosan) or alginate microencapsulated porcine islets were transplanted into diabetic mice. The fibrosis infiltration score was calculated from the harvested microcapsules. The harvested microcapsules were stained with trichrome and for insulin and macrophages., Results: No significant differences in glucose-stimulated insulin secretion and islet viability were noted among naked, alginate, and Dexa-chitosan microencapsulated islets. After transplantation of microencapsulated porcine islets, nonfasting blood glucose were normalized in both the Dexa-chitosan and alginate groups until 231 days. The average glucose after transplantation were lower in the Dexa-chitosan group than the alginate group. Pericapsular fibrosis and inflammatory cell infiltration of microcapsules were significantly reduced in Dexa-chitosan compared with alginate microcapsules. Dithizone and insulin were positive in Dexa-chitosan capsules. Although fibrosis and macrophage infiltration was noted on the surface, some alginate microcapsules were stained with insulin., Conclusion: Dexa coating on microcapsules significantly suppressed the fibrotic reaction on the capsule surface after transplantation of xenogenic islets containing microcapsules without any harmful effects on the function and survival of the islets.

Background: Microcapsule is considered as a promising 3D microenvironment for Bone Tissue Engineering (BTE) applications. Microencapsulation of cells in an appropriate scaffold not only protected the cells against excess stress but also promoted cell proliferation and differentiation. Through the current study, we aimed to microcapsulate the human Dental Pulp Stem Cells (hDPSCs) and evaluated the proliferation and osteogenic differentiation of those cells by using MTT assay, qRT-PCR, Alkaline phosphatase, and Alizarine Red S., Results: The SEM results revealed that Alg/Gel microcapsules containing nHA showed a rough and more compact surface morphology in comparison with the Alg/Gel microcapsules. Moreover, the microencapsulation by Alg/Gel/nHA could improve cell proliferation and induce osteogenic differentiation. The cells cultured in the Alg/Gel and Alg/Gel/nHA microcapsules showed 1.4-fold and 1.7-fold activity of BMP-2 gene expression more in comparison with the control group after 21 days. The mentioned amounts for the BMP-2 gene were 2.5-fold and 4-fold more expression for the Alg/Gel and Alg/Gel/nHA microcapsules after 28 days. The nHA, addition to hDPSCs-laden Alg/Gel microcapsule, could up-regulate the bone-related gene expressions of osteocalcin, osteonectin, and RUNX-2 during the 21 and 28 days through the culturing period, too. Calcium deposition and ALP activities of the cells were observed in accordance with the proliferation results as well as the gene expression analysis., Conclusion: The present study demonstrated that microencapsulation of the hDPSCs inside the Alg/Gel/nHA hydrogel could be a potential approach for regenerative dentistry in the near future.

Background: Compounds with biological activities had been reported in the jackfruit. These compounds are susceptible to structural changes such as isomerization and/or loss of bonds due to environmental factors. Then, the encapsulation for protecting is a necessary process., Objective: In this study, encapsulation of High-Value Biological Compounds (HVBC) was performed using High Degree of Polymerization Agave Fructans (HDPAF) and Whey Protein (WP) as encapsulating materials to preserve the biological properties of the HVBC., Methods: The extract was characterized by HPLC-MS in order to show the presence of compounds with preventive or therapeutic effects on chronic degenerative diseases such as cancer. The micrographs by Scanning Electron Microscopy (SEM), Thermal Analysis (TGA and DSC), photostabilization and antiproliferation of M12.C3.F6 cell line of capsules were evaluated., Results: The micrographs of the nanocapsules obtained by Scanning Electron Microscopy (SEM) showed spherical capsules with sizes between 700 and 800nm. No cracks, dents or deformations were observed. The Thermogravimetric Analysis (TGA) evidenced the decomposition of the unencapsulated extract ranging from 154 to 221°C. On the other hand, the fructan-whey protein mixture demonstrated that nanocapsules have a thermoprotective effect because the decomposition temperature of the encapsulated extract increased 32.1°C. Differential Scanning Calorimetry (DSC) exhibited similar values of the glass transition temperature (Tg) between the capsules with and without extract; which indicates that the polymeric material does not interact with the extract compounds. The photoprotection study revealed that nanocapsules materials protect the jackfruit extract compounds from the UV radiation. Finally, the cell viability on the proliferation of M12.C3.F6 cell line was not affected by powder nanocapsules without jackfruit extract, indicating that capsules are not toxic for these cells. However, microcapsules with jackfruit extract (50μg/ml) were able to inhibit significantly the proliferation cells., Conclusion: The encapsulation process provides thermoprotection and photostability, and the antiproliferative activity of HVBC from jackfruit extract was preserved., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Controlled-release formulations (CRFs) have potential applications in modern agriculture, for it can not only prolong the duration of agrochemicals but also alleviate the adverse effect on non-target organism. In this study, we constructed pyraclostrobin@SiO 2 @polydopamine microcapsule (Pyr@SiO 2 @PDA MC). The resulting microcapsule is a near-rod shape (about 1.15 μm), which has a drug-loading efficiency of 55%. Fourier transform infrared (FTIR) and thermogravimetric analysis (TG) revealed the successful entrapment of the pesticide. The coating of polydopamine (PDA) endowing the microcapsule with superior UV-shielding properties than pyraclostrobin@SiO 2 microcapsule (Pyr@SiO 2 MC). Compared with pyraclostrobin emulsifiable concentrate (EC), the Pyr@SiO 2 @PDA MC exhibited 9.07-, 5.50-, 4.93- and 4.16-fold higher fungicidal activity against Rice blast fungus ( Pyricularia oryzae) at concentrations of 0.5, 1, 2 and 4 mg/L. Moreover, acute toxicity tests demonstrated that the sample on zebrafish with lower toxicity on the first day. These results showed that the obtained microcapsule may process broader application potential in agriculture.

The bioactivity of essential oils applied in foods to act as natural preservatives can be reduced due to interactions with other components of the food matrix. Microencapsulation can help to increase the functionality of these compounds. In addition, the electrostatic interaction between proteins and polysaccharides can result in double-layered encapsulating structures, ensuring greater protection to essential oils than using only protein as surface active agent. In this work, pink pepper essential oil was microencapsulated by spray drying of single-layer emulsions, stabilized by soy protein isolate (SPI), and of double-layer emulsions, stabilized by soy protein isolate/high methoxyl pectin (SPI/HMP). Pink pepper essential oil showed predominance of α-pinene, β-pinene, β-mircene, δ-3-carene, d-limonene, and germacrene D. Compared to SPI microcapsules, SPI/HMP microcapsules better preserved the total volatile content identified in pure oil, showed less water adsorption during storage at relative humidity ≥75% and improved antimicrobial properties. When stored for 20 days (25 °C/RH = 52.8%), both microcapsules allowed more gradual release of volatiles compared with non-encapsulated oil. Microencapsulation by spray drying did not have negative effects on the antioxidant activity of the encapsulated oil, as the microcapsules showed similar results to the non-encapsulated oil, around 11 μg Trolox/mg of oil. After storage, however, the non-encapsulated oil showed greater losses of its antioxidant activity due to higher rates of volatile release. In the in vitro antimicrobial activity assay, both microcapsules inhibited growth of Staphylococcus aureus, Bacillus subtilis, Listeria monocytogenes and Listeria innocua, although no inhibition was observed against Gram-negative bacteria. When added in milk, both microcapsules reduced bacterial growth, whereas non-encapsulated oil showed no satisfactory inhibition. Faster reduction of microbial growth in milk was observed for SPI/HMP microcapsules. Inhibition results were better for skim milk than for whole milk, suggesting that the interaction of essential oil with other lipids present in milk decreased its bioactivity. Microencapsulation positively affected the functionality of pink pepper essential oil, highlighting its potential for application as a natural preservative in food products., (Copyright © 2020 Elsevier B.V. All rights reserved.)

An encapsulated formulation of Bacillus thuringiensis (Bt) was produced by the Pickering emulsion technique to improve its activity and stability under UV-A radiation. In this technique latex particles, GO nanosheets, olive oil, ethanol, and water were used to encapsulate Bt in colloidosomes. The protective efficacy of this formulation in protecting Bt subsp. Kurstaki against deactivation by UV-A irradiation was measured, so that spore viability and mortality on Ephestia kuehniella (E. kuehniella) Zeller larvae under UV-A radiation are investigated. According to the results of both tests, encapsulated formulation at a concentration of 0.045% has the highest protection of viability. Hence, colloidosome microcapsule formulations successfully provide good protection against UV radiation.

This work aimed to formulate and perform physicochemical and functional characterization of maltodextrin microcapsules containing ethanolic extract of stevia, rich in antioxidant compounds, encapsulated by a spray-drying process with two maltodextrins (DE10 and DE19). The powders were named M10 and M19, respectively. We analyzed the physicochemical parameters, antidiabetic activity, cytotoxicity, bioaccessibility of the compounds by in vitro digestion, as well as the structure of the microcapsules by scanning electron microscopy. Microcapsules showed higher solubility (∼35%), lower moisture content (∼29%), and the maltodextrin DE10 had higher efficiency as an encapsulating agent (87%) when compared to DE19 (76%) and showed well-defined spherical structures. The microencapsulation preserved the content of phenolic compounds and antioxidant activity present in the extract (7.2% and 87.5%, respectively). The bioaccessibility of these microencapsulated compounds and antioxidant activity were higher under different conditions of in vitro digestion (mouth, gastric, and intestinal conditions) and showed no cytotoxic effects. We identified 41 compounds (by UHPLC-MS/MS-Qtof) related to the nutritional benefits offered by stevia and the microencapsulation technique can be recommended to preserve bioactive compounds. PRACTICAL APPLICATION: Ethanol extract from stevia leaves contains antioxidant phytochemicals related to the nutritional benefits of stevia. However, this extract presents low solubility and consequently low bioaccessibility under in vitro digestion. The microencapsulation process protects the bioactive compounds of the different pH from digestion and improves the physical-chemical parameters of the extract, increasing its applicability as a possible food additive., (© 2020 Institute of Food Technologists®.)

ShuFeng JieDu capsule (SFJDC), a traditional Chinese medicine, has been recommended for the treatment of COVID-19 infections. However, the pharmacological mechanism of SFJDC still remains vague to date. The active ingredients and their target genes of SFJDC were collected from TCMSP. COVID-19 is a type of Novel Coronavirus Pneumonia (NCP). NCP-related target genes were collected from GeneCards database. The ingredients-targets network of SFJDC and PPI networks were constructed. The candidate genes were screened by Venn diagram package for enrichment analysis. The gene-pathway network was structured to obtain key target genes. In total, 124 active ingredients, 120 target genes of SFJDC and 251 NCP-related target genes were collected. The functional annotations cluster 1 of 23 candidate genes (CGs) were related to lung and Virus infection. RELA, MAPK1, MAPK14, CASP3, CASP8 and IL6 were the key target genes. The results suggested that SFJDC cloud be treated COVID-19 by multi-compounds and multi-pathways, and this study showed that the mechanism of traditional Chinese medicine (TCM) in the treatment of disease from the overall perspective., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)