Prenatal but not continued postpartum vitamin D supplementation reduces maternal bone resorption as measured by C-terminal telopeptide of type 1 collagen without effects on other biomarkers of bone metabolism.

Vitamin D is a key regulator of bone mineral homeostasis and may modulate maternal bone health during pregnancy and postpartum. Using previously-collected data from the Maternal Vitamin D for Infant Growth (MDIG) trial in Dhaka, Bangladesh, we aimed to investigate the effects of prenatal and postpartum vitamin D3 supplementation on circulating biomarkers of bone formation and resorption at delivery and 6 months postpartum. MDIG trial participants were randomized to receive a prenatal;postpartum regimen of placebo or vitamin D3 (IU/week) as either 0;0 (Group A), 4200;0 (B), 16,800;0 (C), 28,000;0 (D) or 28,000;28,000 (E) from 17 to 24 weeks' gestation to 6 months postpartum. As this sub-study was not pre-planned, the study sample included MDIG participants who had data for at least 1 biomarker of interest at delivery or 6 months postpartum, with a corresponding baseline measurement (n = 690; 53 % of 1300 enrolled trial participants). Biomarkers related to bone turnover were measured in maternal venous blood samples collected at enrolment, delivery, and 6 months postpartum: osteoprotegerin (OPG), osteocalcin (OC), receptor activator nuclear factor kappa-B ligand (RANKL), fibroblast growth factor 23 (FGF23), procollagen type 1 N-terminal propeptide, (P1NP) and carboxy terminal telopeptide of type 1 collagen (CTx). Supplementation effects were expressed as percent differences between each vitamin D group and placebo with 95 % confidence intervals (95 % CI). Of 690 participants, 64 % had 25-hydroxyvitamin D concentrations (25OHD) <30 nmol/L and 94 % had 25OHD < 50 nmol/L at trial enrolment. At delivery, mean CTx concentrations were 27 % lower in group E versus placebo (95 % CI: -38, -13; P < 0.001), adjusting for enrolment concentrations. However, at 6 months postpartum, CTx concentrations were not statistically different in group E versus placebo (14 %; 95 % CI: -5.3, 37; P = 0.168), adjusting for delivery CTx concentrations. Effects on other biomarkers at delivery or postpartum were not statistically significant. In conclusion, prenatal high-dose vitamin D supplementation reduced bone resorption during pregnancy, albeit by only one biomarker, and without evidence of a sustained effect in the postpartum period. However, further evidence is needed to substantiate potential maternal bone health benefits of vitamin D in the postpartum period.

Sophoridine exerts anti-arthritic effects on fibroblast-like synoviocytes and collagen-induced arthritis in rats.

The discovery of alternative medicines with fewer adverse effects is urgently needed for rheumatoid arthritis (RA). Sophoridine (SR), the naturally occurring quinolizidine alkaloid isolated from the leguminous sophora species, has been demonstrated to possess a wide range of pharmacological activities. However, the effect of SR on RA remains unknown. In this study, the collagen-induced arthritis (CIA) rat model and tumor necrosis factor alpha (TNFα)-induced fibroblast-like synoviocytes (FLSs) were utilized to investigate the inhibitory effect of SR on RA. The anti-arthritic effect of SR was evaluated using the CIA rat model in vivo and TNFα-stimulated FLSs in vitro. Mechanistically, potential therapeutic targets and pathways of SR in RA were analyzed through drug target databases and disease databases, and validation was carried out through immunofluorescence, immunohistochemistry, and Western blot. The in vivo results revealed that SR treatment effectively ameliorated synovial inflammation and bone erosion in rats with CIA. The in vitro studies showed that SR could significantly suppress the proliferation and migration in TNFα-induced arthritic FLSs. Mechanistically, SR treatment efficiently inhibited the activation of MAPKs (JNK and p38) and NF-κB pathways in TNFα-induced arthritic FLSs. These findings were further substantiated by Immunohistochemistry results in the CIA rat. SR exerts an anti-arthritic effect in CIA rats through inhibition of the pathogenic characteristic of arthritic FLSs via suppressing NF-κB and MAPKs (JNK and p38) signaling pathways. SR may have a great potential for development as a novel therapeutic agent for RA treatment.

Feasibility of Enzymatic Protein Extraction from a Dehydrated Fish Biomass Obtained from Unsorted Canned Yellowfin Tuna Side Streams: Part II.

The enzymatic extraction of proteins from fish biomasses is being widely investigated. However, little or almost no research has paid attention to the exploitation of unsorted fishery biomasses. This work is part of a larger study, Part I of which has already been published, and focuses on an extensive characterization of two collagenous samples, namely gelatin (G) and hydrolyzed gelatin peptides (HGPs), extracted from a dehydrated fish biomass coming from unsorted canned yellowfin tuna side streams. The results indicate crude protein fractions of 90-93%, pH values between 3 and 5, white-yellow colors, collagen-like FTIR spectra, and 17% in terms of total amino acid content. Viscosity and the study of dynamic viscous-elastic behavior were analyzed. Thermo-gravimetric analysis was performed to assess the residual ashes. Both samples were investigated to determine their molecular weight distribution via size-exclusion chromatography, with a higher total average molecular weight for G compared to HGPs, with values of 17,265.5 Da and 2637.5 Da, respectively. G demonstrated technological properties similar to analogous marine gelatins. HGPs demonstrated antioxidant activity as per FRAP assay. All the results open up new perspectives for the potential use of these substances in biodegradable packaging, dietary supplements, and skin care cosmetics.

Nuciferine alleviates collagen-induced arthritic in rats by inhibiting the proliferation and invasion of human arthritis-derived fibroblast-like synoviocytes and rectifying Th17/Treg imbalance.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by persistent synovial inflammation and joint degradation, posing challenges in the development of effective treatments. Nuciferine, an alkaloid found in lotus leaf, has shown promising anti-inflammatory and anti-tumor effects, yet its efficacy in RA treatment remains unexplored. This study investigated the antiproliferative effects of nuciferine on the MH7A cell line, a human RA-derived fibroblast-like synoviocyte, revealing its ability to inhibit cell proliferation, promote apoptosis, induce apoptosis, and cause G1/S phase arrest. Additionally, nuciferine significantly reduced the migration and invasion capabilities of MH7A cells. The therapeutic potential of nuciferine was further evaluated in a collagen-induced arthritis (CIA) rat model, where it markedly alleviated joint swelling, synovial hyperplasia, cartilage injury, and inflammatory infiltration. Nuciferine also improved collagen-induced bone erosion, decreased pro-inflammatory cytokines and serum immunoglobulins (IgG, IgG1, IgG2a), and restored the balance between T helper (Th) 17 and regulatory T cells in the spleen of CIA rats. These results indicate that nuciferine may offer therapeutic advantages for RA by decreasing the proliferation and invasiveness of FLS cells and correcting the Th17/Treg cell imbalance in CIA rats.

Natural products - Dawn of keloid treatment.

Keloids are prevalent pathological scars, often leading to cosmetic deformities and hindering joint mobility.They cause discomfort, including burning and itching, while gradually expanding and potentially posing a risk of cancer.Developing effective drugs and treatments for keloids has been a persistent challenge in the medical field. Natural products are an important source of innovative drugs and a breakthrough for many knotty disease.Herein, keywords of "natural, plant, compound, extract" were combined with "keloid" and searched in PubMed and Google Scholar, respectively. A total of 32 natural products as well as 9 extracts possessing the potential for treating keloids were ultimately identified.Current research in this field faces a significant challenge due to the lack of suitable animal models, resulting in a predominant reliance on in vitro studies.In vivo and clinical studies are notably scarce as a result.Moreover, there is a notable deficiency in research focusing on the role of nutrients in keloid formation and treatment.The appropriate dosage form (oral, topical, injectable) is crucial for the development of natural product drugs. Finally, the conclusion was hereby made that natural products, when used as adjuncts to other treatments, hold significant potential in the management of keloids.By summarizing the natural products and elucidating their mechanisms in keloid treatment, the present study aims to stimulate further discoveries and research in drug development for effectively addressing this challenging condition.

Emodin ameliorates myocardial fibrosis in mice by inactivating the ROS/PI3K/Akt/mTOR axis.

BACKGROUND: Emodin is a traditional medicine that has been shown to exert anti-inflammatory and anti-oxidative effects. Previous research has indicated that emodin can alleviate myocardial remodeling and inhibit myocardial hypertrophy and fibrosis. However, the mechanism by which emodin affects myocardial fibrosis (MF) has not yet been elucidated. METHODS: Fibroblasts were treated with ANGII, and a mouse model of MF was established by ligation of the left anterior descending coronary artery. Cell proliferation was examined by a Cell Counting Kit-8 (CCK8) assay. Dihydroethidium (DHE) was used to measure reactive oxygen species (ROS) levels, and Masson and Sirius red staining were used to examine changes in collagen fiber levels. PI3K was over-expressed by lentiviral transfection to verify the effect of emodin on the PI3K/AKT/mTOR signaling axis. Changes in cardiac function in each group were examined by echocardiography. RESULTS: Emodin significantly inhibited fibroblast proliferation, decreased intracellular ROS levels, significantly upregulated collagen II expression, downregulated α-SMA expression, and inhibited PI3K/AKT/mTOR pathway activation in vitro. Moreover, the in vivo results were consistent with the in vitro. Emodin significantly decreased ROS levels in heart tissue and reduced collagen fibrillogenesis. Emodin could regulate the activity of PI3K to increase the expression of collagen II and downregulate α-SMA expression in part through the PI3K/AKT/mTOR pathway, and emodin significantly improved cardiac structure and function in mice. CONCLUSIONS: This study revealed that emodin targeted the PI3K/AKT/mTOR pathway to inhibit the development of myocardial fibrosis and may be an antifibrotic agent for the treatment of cardiac fibrosis.

Insulin-transferrin-selenium promote formation of tissue-engineered vascular grafts in early stage of culture.

To create tissue-engineered vascular grafts (TEVGs) in vitro, vascular smooth muscle cells (VSMCs) must function effectively and produce sufficient extracellular matrix (ECM) in a three-dimensional space. In this study, we investigated whether the addition of insulin-transferrin-selenium (ITS), a medium supplement, could enhance TEVG formation. PGA fabric was used as the scaffold, and 1% ITS was added to the medium. After two weeks, the tissues were examined using electron microscopy and staining. The ITS group exhibited a denser structure and increased collagen production. VSMCs were cultured in two dimensions with ITS and assessed for collagen production, cell growth, and glucose metabolism. The results showed that ITS supplementation increased collagen production, cell growth, glucose utilization, lactate production, and ATP levels. Furthermore, reducing the amount of fetal bovine serum (FBS) in the medium did not affect the TEVGs or VSMCs when ITS was present. In conclusion, ITS improves TEVG construction by promoting VSMCs growth and reducing the need for FBS.

Association of a Skin Dressing Made With the Organic Part of Marine Sponges and Photobiomodulation on the Wound Healing in an Animal Model.

The present study aims to characterize and to evaluate the biological effects of a skin dressing manufactured with the organic part of the Chondrilla caribensis marine sponge (called spongin-like collagen (SC)) associated or not to photobiomodulation (PBM) on the skin wound healing of rats. Skin dressings were manufactured with SC and it was characterized using scanning electron microscopy (SEM) and a tensile assay. In order to evaluate its biological effects, an experimental model of cutaneous wounds was surgically performed. Eighteen rats were randomly distributed into three experimental groups: control group (CG): animals with skin wounds but without any treatment; marine collagen dressing group (DG): animals with skin wounds treated with marine collagen dressing; and the marine collagen dressing + PBM group (DPG): animals with skin wounds treated with marine collagen dressing and PBM. Histopathological, histomorphometric, and immunohistochemical evaluations (qualitative and semiquantitative) of COX2, TGFß, FGF, and VEGF were done. SEM demonstrates that the marine collagen dressing presented pores and interconnected fibers and adequate mechanical strength. Furthermore, in the microscopic analysis, an incomplete reepithelialization and the presence of granulation tissue with inflammatory infiltrate were observed in all experimental groups. In addition, foreign body was identified in the DG and DPG. COX2, TGFß, FGF, and VEGF immunostaining was observed predominantly in the wound area of all experimental groups, with a statistically significant difference for FGF immunostaining score of DPG in relation to CG. The marine collagen dressing presented adequate physical characteristics and its association with PBM presented favorable biological effects to the skin repair process.

Treatment with synchronized radiofrequency and facial muscle stimulation: Histologic analysis of human skin for changes in collagen and elastin fibers.

BACKGROUND: Skin's exposure to intrinsic and extrinsic factors causes age-related changes, leading to a lower amount of dermal collagen and elastin. AIM: This study investigated the effects of a novel facial muscle stimulation technology combined with radiofrequency (RF) heating on dermal collagen and elastin content for the treatment of facial wrinkles and skin laxity. METHODS: The active group subjects (N = 6) received four 20-min facial treatments with simultaneous RF and facial muscle stimulation, once weekly. The control subject (N = 1) was untreated. Skin biopsies obtained at baseline, 1-month and 3-month follow-up were evaluated histologically to determine collagen and elastin fibers content. A group of independent aestheticians evaluated facial skin appearance and wrinkle severity. Patient safety was followed. RESULTS: In the active group, collagen-occupied area reached 11.91 ± 1.80 × 106 µm2 (+25.32%, p < 0.05) and 12.35 ± 1.44 × 105 µm2 (+30.00%, p < 0.05) at 1-month and 3-month follow-up visits. Elastin-occupied area at 1-month and 3-month follow-up was 1.64 ± 0.14 × 105 µm2 (+67.23%, p < 0.05), and 1.99 ± 0.21 × 105 µm2 (+102.80%, p < 0.05). In the control group, there was no significant difference (p > 0.05) in collagen and elastin fibers. Active group wrinkle scores decreased from 5 (moderate, class II) to 3 (mild, class I). All subjects, except the control, improved in appearance posttreatment. No adverse events or side effects occurred. CONCLUSION: Decreased dermal collagen and elastin levels contributes to a gradual decline in skin elasticity, leading to facial wrinkles and unfirm skin. Study results showed noticeable improvement in facial appearance and increased dermal collagen and elastin content subsequent to simultaneous, noninvasive RF, and facial muscle stimulation treatments.

Efficacy and Safety of Spinal Collagen Mesotherapy in Patients with Chronic Low Back Pain in a Three-Month Follow-Up-Retrospective Study.

Background: Low back pain syndrome is associated with muscular and myofascial pain and is linked with muscle overstrain or a lack of regular physical activity as well as a habitual bad posture, which cause the overload of perispinal soft tissues. One of the forms of therapy of LBP is the mesotherapy of the spine, which consists of multi-point micro-injections of drugs or medicine mixtures, which include preparations of collagen type I. The aim of the study was to assess the efficacy and safety of mesotherapy with collagen type I. Methods: A retrospective analysis of the results of the treatment of patients with chronic low back pain syndrome using mesotherapy was performed. A total of 130 patients (83 women and 47 men; mean age: 51 ± 14 years) were divided into two groups: group I (n = 65), treated with collagen type I, and group II (n = 65), treated with lignocaine 1%. Mesotherapy was performed weekly over five weeks. Patients were assessed using the following scales: the VAS, Laitinen Scale, and Revised Oswestry Low Back Pain Disability Scale before the start of the treatment, after five treatments, and at the three-month follow-up visit. Results: A statistically significant improvement was observed after the use of spinal mesotherapy both with collagen type I and lignocaine, with the collagen treatment having better results at the three-month follow-up visit. No adverse effects were observed after the procedures. Conclusions: Spinal mesotherapy using collagen type I and lignocaine seems to be an effective method in the treatment of chronic LBP. Collagen mesotherapy gives better results in the long term. Mesotherapy is a safe form of therapy.

Dietary Isoeugenol Supplementation Attenuates Chronic UVB-Induced Skin Photoaging and Modulates Gut Microbiota in Mice.

Photoaging, the primary cause of skin aging damage, results from chronic ultraviolet (UV) exposure, leading to dryness and wrinkle formation. Nutritional intervention has emerged as a practical approach for preventing and addressing the effect of skin photoaging. The primary aromatic compound isolated from clove oil, isoeugenol (IE), has antibacterial, anti-inflammatory, and antioxidant qualities that work to effectively restrict skin cancer cell proliferation. This investigation delved into the advantages of IE in alleviating skin photoaging using UVB-irradiated skin fibroblasts and female SKH-1 hairless mouse models. IE alleviated UVB-induced photodamage in Hs68 dermal fibroblasts by inhibiting matrix metalloproteinase secretion and promoting extracellular matrix synthesis. In photoaged mice, dietary IE reduced wrinkles, relieved skin dryness, inhibited epidermal thickening, and prevented collagen loss. Additionally, the intestinal dysbiosis caused by prolonged UVB exposure was reduced with an IE intervention. The results of Spearman's analysis showed a strong correlation between skin photoaging and gut microbiota. Given the almost unavoidable UVB exposure in contemporary living, this research demonstrated the efficacy of dietary IE in reversing skin photoaging, presenting a promising approach to tackle concerns related to extrinsic skin aging.

The Effects In Vitro of Photobiomodulation Over Fibroblasts and Extracellular Matrix.

Objective: The objective of this study is to evaluate the potential effects of photobiomodulation (PBM) on cell proliferation and extracellular matrix production of human fibroblasts (FN1) cultured in 2D. Background: Patients with healing difficulties suffer injuries that take time to recover. In addition, aging can be seen in our faces daily when we look in the mirror; in both situations, collagen production is reduced. Fibroblasts act in the beginning and at the end of the inflammation phase, signaling to immune agents, and platelets, and producing collagen, coordinating repair. PBM increases cell viability, proliferation, and mRNA production. Methods: Human fibroblasts were irradiated three times after cell seed (after 24, 48, and 72 h) using a gallium-aluminum arsenideGaAlAs low-level laser (LLL). Cell viability, proliferative response, synthesis of collagen types I and III, and soluble collagen production were analyzed. The statistical significance of differences between groups was determined using unpaired one-way analysis of variance (ANOVA) p < 0.05. Results: PBM increased significantly the number of fibroblasts, and the production of collagen types I (Col I) and III (Col III), after three sessions of LLL with 2.5 J per session, every 24 h, for 3 consecutive days; total energy delivered after 72 h is 7.5 J. Conclusions: This energy density of LLL increases fibroblast proliferation and collagen production in vitro without side effects.

The study of wound healing activity of Thespesia populnea L. bark, an approach for accelerating healing through nanoparticles and isolation of main active constituents.

The present study provides an evaluation for the wound healing activity of the ethanolic extract of Thespesia populnea L. bark (EBE) and its successive fractions in two doses level (1&2%), designed for determining the most bioactive fraction and the suitable dose. Furthermore, development of the most convenient formulation for these bioactive fractions through either their direct incorporation into hydrogel formulations or incorporation of chitosan-loaded nanoparticles with these bioactive fractions into hydrogel formulations. The highest excision wound healing activity was observed in petroleum ether (Pet-B) followed by ethyl acetate (Etac-B) fractions at the high dose (2%). The most suitable formulation designed for the Etac-B fraction was found to be the chitosan-loaded nanoparticles incorporated in the hydrogel formulation, while the conventional hydrogel formulation was observed to be the highly acceptable formulation for Pet-B fraction. Further phytochemical studies of the bioactive fractions led to the isolation of many compounds of different chemical classes viz; beta-sitosterol and lupeol acetate isolated from the Pet-B, in addition to cyanidin and delphinidin from the Etac-B. Our results revealed that EBE and its bioactive fractions (Pet-B & Etac-B) could be considered as strong wound healers through their anti-oxidant and anti-inflammatory activities, in addition to stimulating collagen synthesis.

Natural compound library screening to identify berberine as a treatment for rheumatoid arthritis.

OBJECTIVE: Fibroblast-like synoviocytes (FLS) play a critical role on the exacerbation and deterioration of rheumatoid arthritis (RA). Aberrant activation of FLS pyroptosis signaling is responsible for the hyperplasia of synovium and destruction of cartilage of RA. This study investigated the screened traditional Chinese medicine berberine (BBR), an active alkaloid extracted from the Coptis chinensis plant, that regulates the pyroptosis of FLS and secretion of inflammatory factors in rheumatoid arthritis. METHODS: First, BBR was screened using a high-throughput drug screening strategy, and its inhibitory effect on RA-FLS was verified by in vivo and in vitro experiments. Second, BBR was intraperitoneally administrated into the collagen-induced arthritis rat model, and the clinical scores, arthritis index, and joint HE staining were evaluated. Third, synovial tissues of CIA mice were collected, and the expression of NLRP3, cleaved-caspase-1, GSDMD-N, Mst1, and YAP was detected by Western blot. RESULTS: The administration of BBR dramatically alleviated the severity of collagen-induced arthritis rat model with a decreased clinical score and inflammation reduction. In addition, BBR intervention significantly attenuates several pro-inflammatory cytokines (interleukin-1ß, interleukin-6, interleukin-17, and interleukin-18). Moreover, BBR can reduce the pyroptosis response (caspase-1, NLR family pyrin domain containing 3, and gasdermin D) of the RA-FLS in vitro, activating the Hippo signaling pathway (Mammalian sterile 20-like kinase 1, yes-associated protein, and transcriptional enhanced associate domains) so as to inhibit the pro-inflammatory effect of RA-FLS. CONCLUSION: These results support the role of BBR in RA and may have therapeutic implications by directly repressing the activation, migration of RA-FLS, which contributing to the attenuation of the progress of CIA. Therefore, targeting PU.1 might be a potential therapeutic approach for RA. Besides, BBR inhibited RA-FLS pyroptosis by downregulating of NLRP3 inflammasomes (NLRP3, caspase-1) and eased the pro-inflammatory activities via activating the Hippo signaling pathway, thereby improving the symptom of CIA.

Minimizing pain in deer antler removal: Local anaesthetics in ZnO nanoparticle based collagen dressings as a promising solution.

Antler removal in deer is a common practice for various purposes, including meat production and traditional medicine. However, the current industry practice using lidocaine as a local anesthetic has limitations, such as short duration of action and the potential for postoperative infections. In this study, we investigated the performance of a ZnO collagen nanocomposites loaded with local anesthetics to improve wound management and alleviate pain associated with antler removal in red deer. The research involved the preparation of collagen nanocomposites with local anesthetics and testing the drug release rates using in vitro drug release tests. Pharmacokinetic analysis was performed to evaluate the total drug release from the collagen matrix in red deer after velvet removal. Additionally, the analgesic efficacy of these collagen nanocomposite dressings was assessed after antler removal in red deer. Functionalized ZnO nanoparticles were incorporated into collagen fibers to enhance their mechanical stability and prolong drug release. The developed collagen nanocomposites aimed to slowly release local anesthetics and promote wound healing. The findings of this research could have significant implications for improving the pain management and wound healing associated with antler removal in deer. The results obtained from the in vitro drug release tests, pharmacokinetic analysis, and analgesic efficacy evaluations provide valuable insights into the understanding and development of novel approaches for antler removal procedures in red deer. The findings contribute to the advancement of knowledge in this field and lay the foundation for future implementation of improved techniques and protocols for antler removal.

Organic-inorganic biohybrid films from wool-keratin/jellyfish-collagen/silica/boron via sol-gel reactions for soft tissue engineering applications.

Therapeutic angiogenesis is pivotal in creating effective tissue-engineered constructs that deliver nutrients and oxygen to surrounding cells. Hence, biomaterials that promote angiogenesis can enhance the efficacy of various medical treatments, encompassing tissue engineering, wound healing, and drug delivery systems. Considering these, we propose a rapid method for producing composite silicon-boron-wool keratin/jellyfish collagen (Si-B-WK/JFC) inorganic-organic biohybrid films using sol-gel reactions. In this approach, reactive tetraethyl orthosilicate and boric acid (pKa ⩾ 9.24) were used as silicon and boron sources, respectively, and a solid-state gel was formed through the condensation reaction of these reactive groups with the keratin/collagen mixture. Once the resulting gel was thoroughly suspended in water, the films were prepared by a casting/solvent evaporation methodology. The fabricated hybrid films were characterized structurally and mechanically. In addition, angiogenic characteristics were determined by the in ovo chick chorioallantoic membrane assay, which revealed an increased vascular network within the Si-B-WK/JFC biohybrid films. In conclusion, it is believed that Si-B-WK/JFC biohybrid films with mechanical and pro-angiogenic properties have the potential to be possessed in soft tissue engineering applications, especially wound healing.

MHC-DRB alleles with amino acids Val11, Phe13, and the shared epitopes promote collagen-induced arthritis and a rapid IgG1 response in Filipino cynomolgus macaques.

Macaques are useful animal models for studying the pathogenesis of rheumatoid arthritis (RA) and the development of anti-rheumatic drugs. The purpose of this study was to identify the major histocompatibility complex (MHC) polymorphisms associated with the pathology of collagen-induced arthritis (CIA) and anti-collagen IgG induction in a cynomolgus macaque model, as MHC polymorphisms affect the onset of CIA in other animal models. Nine female Filipino cynomolgus macaques were immunized with bovine type II collagen (b-CII) to induce CIA, which was diagnosed clinically by scoring the symptoms of joint swelling over 9 weeks. MHC polymorphisms and anti-b-CII antibody titers were compared between symptomatic and asymptomatic macaques. Four of 9 (44%) macaques were defined as the CIA-affected group. Anti-b-CII IgG in the affected group increased in titer approximately 3 weeks earlier compared with the asymptomatic group. The mean plasma IgG1 titer in the CIA-affected group was significantly higher (p < 0.05) than that of the asymptomatic group. Furthermore, the cynomolgus macaque MHC (Mafa)-DRB1*10:05 or Mafa-DRB1*10:07 alleles, which contain the well-documented RA-susceptibility five amino acid sequence known as the shared epitope (SE) in positions 70 to 74, with valine at position 11 (Val11, V11) and phenylalanine at position 13 (Phe13, F13), were detected in the affected group. In contrast, no MHC polymorphisms specific to the asymptomatic group were identified. In conclusion, the presence of V11 and F13 along with SE in the MHC-DRB1 alleles seems essential for the production of IgG1 and the rapid induction of severe CIA in female Filipino cynomolgus macaques.

In Vitro Safety and Efficacy Evaluation of a Juniperus communis Callus Culture Extract and Matricaria recutita Processing Waste Extract Combination as a Cosmetic Ingredient.

For skin health promotion and cosmetic applications, combinations of plant cell extracts are extensively utilized. As most natural ingredient suppliers offer crude extracts from individual plants or specific isolated compounds, the potential interactions between them are assessed in the development phase of cosmetic products. The industry seeks extract combinations that have undergone optimization and scrutiny for their bioactivities. This study presents a combination of two sustainably produced botanical ingredients and outlines their chemical composition, in vitro safety, and bioactivity for skin health enhancement. The amalgamation comprises the extract of Matricaria recutita processing waste and the extract from Juniperus communis callus culture. Chemical analysis revealed distinct compounds within the extracts, and their combination led to a broader array of potentially synergistic compounds. In vitro assessments on skin cells demonstrated that the combination possesses robust antioxidant properties and the ability to stimulate keratinocyte proliferation, along with regulating collagen type I and matrix metalloproteinase 1 (MMP-1) production by dermal fibroblasts. The identified traits of this combination render it an appealing cosmetic component. To the best of our knowledge, this represents the first case when the extracts derived from medicinal plant processing waste and biotechnological plant cell cultivation processes have been combined and evaluated for their bioactivity.

Berberine modulates the immunometabolism and differentiation of CD4+ T cells alleviating experimental arthritis by suppression of M1-exo-miR155.

BACKGROUND: The inflammatory cascade mediated by macrophages and T cells is considered to be an important factor in promoting the progression of rheumatoid arthritis (RA). Our previous study found that berberine (BBR) can therapeutically impact adjuvant arthritis (AA) in rats through the regulation of macrophage polarization and the balance of Th17/Treg. However, whether BBR's effects on CD4+T cells response are related to its suppression of M1 macrophage still unclear. PURPOSE: The study aimed to estimate the mechanism of BBR in regulating the immunometabolism and differentiation of CD4+T cells are related to exosome derived from M1-macrophage (M1-exo). STUDY-DESIGN/METHODS: Mice model of collagen-induced arthritis (CIA) was established to investigate the antiarthritic effect of BBR was related with regulation of M1-exo to balance T cell subsets. Bioinformatics analysis using the GEO database and meta-analysis. In vitro, we established the co-culture system involving M1-exo and CD4+ T cells to examine whether BBR inhibits CD4+T cell activation and differentiation by influencing M1-exo-miR155. Exosome was characterized using transmission electron microscopy and western blot analysis, macrophage and CD4+T cell subpopulation were detected by flow cytometry. Further, the metabolic profiles of CD4+T cells were assessed by ECAR, OCR, and the level of glucose, lactate, intracellular ATP. RESULT: BBR reinstates CD4+ T cell homeostasis and reduces miR155 levels in both M1-exo and CD4+ T cells obtained from mice with CIA. In vitro, we found exosomes are indispensable for M1-CM on T lymphocyte activation and differentiation. BBR reversed M1-exo facilitating the activation and differentiation of CD4+T cells. Furthermore, BBR reversed glycolysis reprogramming of CD4+T cells induced by M1-exo, while these regulation effects were significantly weakened by miR155 mimic. CONCLUSION: The delivery of miR-155 by M1-exo contributes to CD4+ T cell immunometabolism dysfunction, a process implicated in the development of RA. The anti-arthritic effect of BBR is associated with the suppression of glycolysis and the disruption of CD4+ T cell subsets balance, achieved by reducing the transfer of M1-exo-miR155 into T cells.

Management and Amelioration of Knee Joint Osteoarthritis in Adults Using a Novel High-Functional Bovine Collagen Peptide as a Nutritional Therapy: A Double-Blind, Prospective, Multicentric, Randomized, Active and Placebo Controlled, Five-Arm, Clinical Study to Evaluate the Efficacy, Safety, and Tolerability.

OBJECTIVE: The various functionalities of collagen peptides have generated a large interest in utilizing the bioactive peptides as a nutritional therapy to ameliorate various physiological degenerative conditions. Collagen peptides are observed to reduce the pain and aligned difficulties with respect to osteoarthritis. Here we report the enhanced ameliorating property of novel high-functional "Wellnex" Type J collagen peptides following a double-blind randomized active and placebo-controlled 5-arm clinical trial (n = 100) by using it as a nutritional supplement in subjects with knee joint osteoarthritis in comparison with conventional bovine collagen peptides. The efficacy, safety, and tolerability were also studied. DESIGN: Dosages of 2.5, 5.0, and 10.0 g of high-functional Type J bovine collagen peptides, 10.0 g of conventional collagen peptides, and 10.0 g of placebo were given to the 5 groups for a period of 90 days. The Western Ontario McMaster Universities Arthritis Index (WOMAC) score, Pain Scale, Quality of Life (QoL), Physician's Impression of change Score (PICS), serum C-terminal cross-linked telopeptide of type II collagen (CTX-II) levels and Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) parameters were monitored. RESULTS: Type J 2.5 g showed significant improvement in WOMAC, QoL, CTX, and MOAKS and observed to be equivalent to conventional collagen peptide 10-g supplementation in terms of efficacy. CONCLUSION: The two significant outcomes of the study were that Type J 10.0 g, Type J 5.0 g, Type J 2.5 g and conventional collagen peptides 10.0 g supplementation were observed to be beneficial nutraceutical therapies for knee joint osteoarthritis, and Type J 2.5 g supplementation was equivalent to conventional collagen peptides 10.0-g supplementation in terms of efficacy.