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Scientific Reports Jun 2024Delivery of therapeutic stem cells to treat bone tissue damage is a promising strategy that faces many hurdles to clinical translation. Among them is the design of a...
Delivery of therapeutic stem cells to treat bone tissue damage is a promising strategy that faces many hurdles to clinical translation. Among them is the design of a delivery vehicle which promotes desired cell behavior for new bone formation. In this work, we describe the use of an injectable microporous hydrogel, made of crosslinked gelatin microgels, for the encapsulation and delivery of human mesenchymal stem cells (MSCs) and compared it to a traditional nonporous injectable hydrogel. MSCs encapsulated in the microporous hydrogel showed rapid cell spreading with direct cell-cell connections whereas the MSCs in the nonporous hydrogel were entrapped by the surrounding polymer mesh and isolated from each other. On a per-cell basis, encapsulation in microporous hydrogel induced a 4 × increase in alkaline phosphatase (ALP) activity and calcium mineral deposition in comparison to nonporous hydrogel, as measured by ALP and calcium assays, which indicates more robust osteogenic differentiation. RNA-seq confirmed the upregulation of the genes and pathways that are associated with cell spreading and cell-cell connections, as well as the osteogenesis in the microporous hydrogel. These results demonstrate that microgel-based injectable hydrogels can be useful tools for therapeutic cell delivery for bone tissue repair.
Topics: Mesenchymal Stem Cells; Osteogenesis; Humans; Hydrogels; Cell Differentiation; Porosity; Alkaline Phosphatase; Cells, Cultured; Cell Encapsulation; Mesenchymal Stem Cell Transplantation; Injections
PubMed: 38918510
DOI: 10.1038/s41598-024-65731-9 -
PloS One 2024Young calves are more susceptible to cold than older animals due to their limited ability to regulate body temperature and lack of fat reserves and may have difficulty...
Young calves are more susceptible to cold than older animals due to their limited ability to regulate body temperature and lack of fat reserves and may have difficulty consuming the energy needed to cope with the cold by maintaining body temperature and meeting their metabolic needs, especially when fed constant levels of waste milk (WM) with less solids, which can be detrimental to health and future performance. An alternative to overcome this problem is increasing the milk's solids content to the existing volume by using different sources [milk replacer powder (MR) or transition milk (TM)]. Thus, we aimed to evaluate the effects of increasing the total solids of WM via MR (WM+MR) or TM (WM+TM) on the performance, feeding behavior, and health-related variables of cold-stressed dairy calves during pre- and post-weaning. We hypothesized that feeding WM supplemented with MR or TM as potential liquid feed enhancers would improve milk dry matter and energy intake of the calves with a positive impact on body development and have no negative impact on feeding behavior and health. Additionally, we hypothesized that MR would not differ from TM. As a sample size calculation at 80% power using power analysis (PROC POWER) in SAS 9.4, a total of 51 Holstein-Friesian vigorous male calves [vigor score 21-27; 17 per treatment; 4-d old; body weight (BW) = 40.0 ± 0.63 kg (mean ± SD)] were selected, assigned randomly to treatments, and housed in individual pens in an outdoor barn. Irrespective of the type of treatment, all calves were fed 6 kg/d liquid feed from d 1 to d 53 of the experiment. In a step-down weaning program, calves received 0.5 kg liquid feed from d 54 to d 60. All calves were weaned on d 61 and remained in the study until d 101 as post-weaning evaluation. The calves had ad libitum access to starter feed and fresh drinking water across the experiment. Intake, growth, and behavior data were analyzed using a general linear mixed model and health data were analyzed using mixed logistic regression, mixed linear regression, and survival analysis models in SAS. We found that supplementation was responsible for a greater dry matter intake (DMI; P = 0.004), superior average BW (P = 0.037), and increased crude protein (CP; P = 0.001) and crude fat (CF; P = 0.001) intakes, with the most favorable outcomes observed for the WM+TM group when compared with WM+MR. Animals fed WM (control group; CON) showed a smaller average daily gain during the first 40-d of life (P = 0.026), showing slight changes during the whole period of evaluation when compared with the supplemented groups (SUP; WM+MR and WM+TM). No difference between MR- and TM-SUP groups, probability of having abnormal appearance (P = 0.032) and pneumonia occurrence (P = 0.022) was reduced in the SUP than in CON animals, with no effect on diarrhea among treatment groups (P = 0.461). Using milk supplements added to WM is an alternative to improve the intake, performance, and health of young calves under cold stress. Our findings showed that SUP animals outperformed the CON group in terms of DMI, average BW, and intake of CP and CF, with the TM-SUP group displaying the most favorable outcomes. Moreover, the SUP groups demonstrated reduced odds of experiencing abnormal appearance and pneumonia, highlighting the positive impact of supplementation on calf health.
Topics: Animals; Cattle; Milk; Animal Feed; Feeding Behavior; Dietary Supplements; Animals, Newborn; Cold Temperature; Weaning; Female; Male; Milk Substitutes; Powders
PubMed: 38917166
DOI: 10.1371/journal.pone.0305227 -
JAMA Network Open Jun 2024Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are limited.
OBJECTIVE
To assess the effectiveness of sublingual or extended-release injection formulations of buprenorphine for the treatment of OUD among patients with and without fentanyl use.
DESIGN, SETTING, AND PARTICIPANTS
Post hoc analysis of a 24-week, randomized, double-blind clinical trial conducted at 35 outpatient sites in the US from December 2015 to November 2016 of sublingual buprenorphine-naloxone vs extended-release subcutaneous injection buprenorphine (CAM2038) for patients with OUD subgrouped by presence vs absence of fentanyl or norfentanyl in urine at baseline. Study visits with urine testing occurred weekly for 12 weeks, then 6 times between weeks 13 and 24. Data were analyzed on an intention-to-treat basis from March 2022 to August 2023.
INTERVENTION
Weekly and monthly subcutaneous buprenorphine vs daily sublingual buprenorphine-naloxone.
MAIN OUTCOMES AND MEASURES
Retention in treatment, percentage of urine samples negative for any opioids (missing values imputed as positive), percentage of urine samples negative for fentanyl or norfentanyl (missing values not imputed), and scores on opiate withdrawal scales and visual analog craving scales.
RESULTS
Of 428 participants, 123 (subcutaneous buprenorphine, n = 64; sublingual buprenorphine-naloxone, n = 59; mean [SD] age, 39.1 [10.8] years; 75 men [61.0%]) had evidence of baseline fentanyl use and 305 (subcutaneous buprenorphine, n = 149; buprenorphine-naloxone, n = 156; mean [SD] age, 38.1 [11.1] years; 188 men [61.6%]) did not have evidence of baseline fentanyl use. Study completion was similar between the fentanyl-positive (60.2% [74 of 123]) and fentanyl-negative (56.7% [173 of 305]) subgroups. The mean percentage of urine samples negative for any opioid were 28.5% among those receiving subcutaneous buprenorphine and 18.8% among those receiving buprenorphine-naloxone in the fentanyl-positive subgroup (difference, 9.6%; 95% CI, -3.0% to 22.3%) and 36.7% among those receiving subcutaneous buprenorphine and 30.6% among those receiving buprenorphine-naloxone in the fentanyl-negative subgroup (difference, 6.1%; 95% CI, -1.9% to 14.1%), with significant main associations of baseline fentanyl status and treatment group. In the fentanyl-positive subgroup, the mean percentage of urine samples negative for fentanyl during the study was 74.6% among those receiving subcutaneous buprenorphine vs 61.9% among those receiving sublingual buprenorphine-naloxone (difference, 12.7%; 95% CI, 9.6%-15.9%). Opioid withdrawal and craving scores decreased rapidly after treatment initiation across all groups.
CONCLUSIONS AND RELEVANCE
In this post hoc analysis of a randomized clinical trial of sublingual vs extended-release injection buprenorphine for OUD, buprenorphine appeared to be effective among patients with baseline fentanyl use. Patients with fentanyl use had fewer opioid-negative urine samples during the trial compared with the fentanyl-negative subgroup. These findings suggest that the subcutaneous buprenorphine formulation may be more effective at reducing fentanyl use.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02651584.
Topics: Humans; Opioid-Related Disorders; Fentanyl; Male; Female; Administration, Sublingual; Adult; Double-Blind Method; Buprenorphine; Middle Aged; Delayed-Action Preparations; Injections, Subcutaneous; Narcotic Antagonists; Analgesics, Opioid; Opiate Substitution Treatment; Buprenorphine, Naloxone Drug Combination; Treatment Outcome
PubMed: 38916892
DOI: 10.1001/jamanetworkopen.2024.17377 -
TheScientificWorldJournal 2024Pharmaceutical formulations have traditionally relied on plants and their derivatives for various APIs and excipients. In Ghana, the widespread utilization of plantains,...
Pharmaceutical formulations have traditionally relied on plants and their derivatives for various APIs and excipients. In Ghana, the widespread utilization of plantains, irrespective of their ripeness, generates significant waste at every stage of processing, posing disposal issues. Fascinatingly, these wastes, often discarded, possess significant economic potential and can be recycled into valuable raw materials or products. Pectin, a polysaccharide that occurs naturally, has seen a surge in interest in recent times. It has found widespread use in the pharmaceutical sector, particularly as a binding agent in tablet formulations. This study aimed to evaluate pectin from two popular plantain varieties, Apem (M) and Apantu (T) at different ripening stages, for pharmaceutical use as a binding agent in immediate-release tablets. The ripening stages selected were the matured-green (G), half-ripe (H), and full-ripe (R). Acid (D) and alkaline (L) mediums of extraction were employed for each ripening stage for both varieties. Wet granulation method was used to prepare the granules using paracetamol as a model drug, and their flow properties were subsequently assessed. Postcompression tests including, hardness, friability, weight uniformity, disintegration, assay, and in vitro dissolution were also assessed. Granules from all formulation batches had good flow properties indicated by their angle of repose (14.93 ± 1.41-21.80 ± 1.41), Hausner ratio (0.96 ± 0.27-1.22 ± 0.02), and compressibility (%) (7.69 ± 0.002-20.51 ± 0.002). All the tablets passed the uniformity of weight with none deviating by ±5%. The hardness of all the formulated tablets ranged between 3.96 ± 0.32 and 13.21 ± 0.36, while the friability for all tablets was below 1%. The drug content was between 100.1 ± 0.23% and 103.4 ± 0.01%. Tablets formulated with pectin as a binding agent at concentrations of 10% w/v and 15% w/v successfully met the disintegration test criteria for immediate release tablets. However, those prepared with a concentration of 20% w/v (MGL, MHD, MHL, MRD, MRL, TGL, THD, THL, and TRL) did not pass the disintegration test. Consequently, all batches of tablets successfully met the dissolution test requirement (Diss, > 75%), except for the batches that did not pass the disintegration test (Diss, < 75%). Ultimately, pectins extracted from the peels of Apem and Apantu at different ripening stages using acid and alkaline extraction can be commercially exploited as pharmaceutical binders at varying concentrations in immediate-release tablets.
Topics: Pectins; Tablets; Ghana; Plantago; Acetaminophen; Excipients
PubMed: 38915814
DOI: 10.1155/2024/5461358 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Jun 2024Stimuli-responsive liposomes, a novel type of nanocarriers, have been widely used in the fields of medicine, food, and cosmetics. This paper provides a comprehensive... (Review)
Review
Stimuli-responsive liposomes, a novel type of nanocarriers, have been widely used in the fields of medicine, food, and cosmetics. This paper provides a comprehensive introduction to the preparation methods, construction strategies, and biological applications of stimuli-responsive liposomes. The review highlights the functional principles of pH-sensitive, redox-sensitive, enzyme-sensitive, heat-sensitive, light-sensitive, and magnetic field-responsive liposomes, and summarizes their applications based on various drug delivery mode. Finally, the article provides an overview of the current challenges and future development prospects for stimuli-responsive liposomes.
Topics: Liposomes; Drug Delivery Systems; Hydrogen-Ion Concentration; Drug Carriers; Oxidation-Reduction
PubMed: 38914489
DOI: 10.13345/j.cjb.230747 -
Frontiers in Cellular and Infection... 2024Widespread opportunistic pathogens pose a serious threat to global health, particularly in susceptible hospital populations. The escalating crisis of antibiotic...
INTRODUCTION
Widespread opportunistic pathogens pose a serious threat to global health, particularly in susceptible hospital populations. The escalating crisis of antibiotic resistance highlights the urgent need for novel antibacterial agents and alternative treatment approaches. Traditional Chinese Medicine (TCM) and its compounds have deep roots in the treatment of infectious diseases. It has a variety of active ingredients and multi-target properties, opening up new avenues for the discovery and development of antimicrobial drugs.
METHODS
This study focuses on assessing the efficacy of the Shensheng-Piwen changed medicinal powder (SPC) extracts against opportunistic pathogen infections by broth microdilution and agar disc diffusion methods. Additionally, biofilm inhibition and eradication assays were performed to evaluate the antibiofilm effects of SPC extracts.
RESULTS
Metabolite profiles were analyzed by LC-MS. Furthermore, the potential synergistic effect between SPC and Metal-Organic Framework (MOF) was investigated by bacterial growth curve analysis. The results indicated that the SPC extracts exhibited antibacterial activity against , with a minimum inhibitory concentration (MIC) of 7.8 mg/mL (crude drug concentration). Notably, at 1/2 MIC, the SPC extracts significantly inhibited biofilm formation, with over 80% inhibition, which was critical in tackling chronic and hospital-acquired infections. Metabolomic analysis of revealed that SPC extracts induced a notable reduction in the levels of various metabolites, including L-proline, L-asparagine. This suggested that the SPC extracts could interfere with the metabolism of . Meanwhile, the growth curve experiment proved that SPC extracts and MOFs had a synergistic antibacterial effect.
DISCUSSION
In conclusion, the present study highlights the potential of SPC extracts as a novel antibacterial agent against infections, with promising biofilm inhibition properties. The observed synergistic effect between SPC extracts and MOFs further supports the exploration of this combination as an alternative treatment approach.
Topics: Anti-Bacterial Agents; Biofilms; Microbial Sensitivity Tests; Metal-Organic Frameworks; Drugs, Chinese Herbal; Staphylococcus aureus; Drug Synergism; Powders; Humans; Chromatography, Liquid
PubMed: 38912207
DOI: 10.3389/fcimb.2024.1376312 -
Frontiers in Immunology 2024The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and...
The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous . These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic challenges.
Topics: Animals; Nipah Virus; Henipavirus Infections; Ferritins; Mesocricetus; Antibodies, Viral; Antibodies, Neutralizing; Nanoparticles; Viral Vaccines; Cricetinae; Vaccines, Virus-Like Particle; Female; Humans; Nanovaccines
PubMed: 38911870
DOI: 10.3389/fimmu.2024.1387811 -
Frontiers in Immunology 2024Vitamin E, which is also known as tocopherol, is a compound with a polyphenol structure. Its esterified derivative, Vitamin E succinate (VES), exhibits unique anticancer...
BACKGROUND
Vitamin E, which is also known as tocopherol, is a compound with a polyphenol structure. Its esterified derivative, Vitamin E succinate (VES), exhibits unique anticancer and healthcare functions as well as immunomodulatory effects. Natural polysaccharides are proved to be a promising material for nano-drug delivery systems, which show excellent biodegradability and biocompatibility. In this study, we employed a novel polysaccharide-vitamin E succinate polymer (BSP-VES) micelles to enhance the tumor targeting and anti-colon cancer effect of andrographolide (AG).
METHODS
BSP-VES polymer was synthesized through esterification and its structure was confirmed using 1H NMR. AG@BSP-VES was prepared via the dialysis method and the drug loading, entrapment efficiency, stability, and safety were assessed. Furthermore, the tumor targeting ability of AG@BSP-VES was evaluated through targeted cell uptake and imaging. The antitumor activity of AG@BSP-VES was measured using MTT assay, Live&Dead cell staining, and cell scratch test.
RESULTS
In this study, we successfully loaded AG into BSP-VES micelles (AG@BSP-VES), which exhibited good stability, biosafety and sustained release effect. In addition, AG@BSP-VES also showed excellent internalization capability into CT26 cells compared with NCM460 cells . Meanwhile, the specific delivery of AG@BSP-VES micelles into subcutaneous and colon tumors was observed compared with normal colon tissues during the whole experiment process (1-24 h). What's more, AG@BSP-VES micelles exhibited significant antitumor activities than BSP-VES micelles and free AG.
CONCLUSION
The study provides a meaningful new idea and method for application in drug delivery system and targeted treatment of colon cancer based on natural polysaccharides.
Topics: Micelles; Animals; Colonic Neoplasms; Diterpenes; Humans; Mice; Cell Line, Tumor; Polysaccharides; Antineoplastic Agents; Drug Delivery Systems; Xenograft Model Antitumor Assays; Drug Carriers; Nanoparticles; Nanoparticle Drug Delivery System; Mice, Nude; Mice, Inbred BALB C
PubMed: 38911867
DOI: 10.3389/fimmu.2024.1380229 -
International Journal of Nanomedicine 2024Targeted therapy for infantile hemangiomas (IHs) has been extensively studied as they can concentrate drugs, increase therapeutic efficacy and reduce drug dosage.... (Review)
Review
Targeted therapy for infantile hemangiomas (IHs) has been extensively studied as they can concentrate drugs, increase therapeutic efficacy and reduce drug dosage. Meanwhile, they can extend drug release times, enhance drug stability, decrease dosing frequency, and improve patient compliance. Moreover, carriers made from biocompatible materials reduced drug immunogenicity, minimizing adverse reactions. However, current targeted formulations still face numerous challenges such as the non-absolute safety of carrier materials; the need to further increase drug loading capacity; the limitation of animal hemangioma models in fully replicating the biological properties of human infantile hemangiomas; the establishment of models for deep-seated hemangiomas with high incidence rates; and the development of more specific targets or markers. In this review, we provided a brief overview of the characteristics of IHs and summarized the past decade's advances, advantages, and targeting strategies of targeted drug delivery systems for IHs and discussed their applications in the treatment of IHs. Furthermore, the goal is to provide a reference for further research and application in this field.
Topics: Humans; Animals; Hemangioma; Infant; Drug Delivery Systems; Drug Carriers; Antineoplastic Agents
PubMed: 38911507
DOI: 10.2147/IJN.S463119 -
International Journal of Nanomedicine 2024Combination therapy offers superior therapeutic results compared to monotherapy. However, the outcomes of combination therapy often fall short of expectations, mainly...
BACKGROUND
Combination therapy offers superior therapeutic results compared to monotherapy. However, the outcomes of combination therapy often fall short of expectations, mainly because of increased toxicity from drug interactions and challenges in achieving the desired spatial and temporal distribution of drug delivery. Optimizing synergistic drug combination ratios to ensure uniform targeting and distribution across space and time, particularly in vivo, is a significant challenge. In this study, cRGD-coated liposomes encapsulating optimized synergistic cepharanthine (CEP; a chemotherapy drug) and IR783 (a phototherapy agent) were developed for combined chemotherapy and photothermal therapy in vitro and in vivo.
METHODS
An MTT assay was used to evaluate the combination index of CEP and IR783 in five cell lines. The cRGD-encapsulated liposomes were prepared via thin-film hydration, and unencapsulated liposomes served as controls for the loading of CEP and IR783. Fluorescence and photothermal imaging were used to assess the efficacy of CEP and IR783 encapsulated in liposomes at an optimal synergistic ratio, both in vitro and in vivo.
RESULTS
The combination indices of CEP and IR783 were determined in five cell lines. As a proof-of-concept, the optimal synergistic ratio (1:2) of CEP to IR783 in 4T1 cells was evaluated in vitro and in vivo. The average diameter of the liposomes was approximately 100 nm. The liposomes effectively retained the encapsulated CEP and IR783 in vitro at the optimal synergistic molar ratio for over 7 d. In vivo fluorescence imaging revealed that the fluorescence signal from cRGD-CEP-IR783-Lip was detectable at the tumor site at 4 h post-injection and peaked at 8 h. In vivo photothermal imaging of tumor-bearing mice indicated an increase in tumor temperature by 32°C within 200 s. Concurrently, cRGD-CEP-IR783-Lip demonstrated a significant therapeutic effect and robust biosafety in the in vivo antitumor experiments.
CONCLUSION
The combination indices of CEP and IR783 were successfully determined in vitro in five cell lines. The cRGD-coated liposomes encapsulated CEP and IR783 at an optimal synergistic ratio, exhibiting enhanced antitumor effects and targeting upon application in vitro and in vivo. This study presents a novel concept and establishes a research framework for synergistic chemotherapy and phototherapy treatment.
Topics: Liposomes; Animals; Cell Line, Tumor; Humans; Female; Mice; Indoles; Photothermal Therapy; Benzylisoquinolines; Mice, Inbred BALB C; Peptides, Cyclic; Drug Synergism; Antineoplastic Agents; Combined Modality Therapy; Cell Survival; Drug Delivery Systems; Benzodioxoles
PubMed: 38911506
DOI: 10.2147/IJN.S457008