Endogenous chondroitin extends the lifespan and healthspan in C. elegans.

Chondroitin, a class of glycosaminoglycan polysaccharides, is found as proteoglycans in the extracellular matrix, plays a crucial role in tissue morphogenesis during development and axonal regeneration. Ingestion of chondroitin prolongs the lifespan of C. elegans. However, the roles of endogenous chondroitin in regulating lifespan and healthspan mostly remain to be investigated. Here, we demonstrate that a gain-of-function mutation in MIG-22, the chondroitin polymerizing factor (ChPF), results in elevated chondroitin levels and a significant extension of both the lifespan and healthspan in C. elegans. Importantly, the remarkable longevity observed in mig-22(gf) mutants is dependent on SQV-5/chondroitin synthase (ChSy), highlighting the pivotal role of chondroitin in controlling both lifespan and healthspan. Additionally, the mig-22(gf) mutation effectively suppresses the reduced healthspan associated with the loss of MIG-17/ADAMTS metalloprotease, a crucial for factor in basement membrane (BM) remodeling. Our findings suggest that chondroitin functions in the control of healthspan downstream of MIG-17, while regulating lifespan through a pathway independent of MIG-17.

Preparation and evaluation of spray-dried inhalable microparticles from carrier mixtures.

The formulation of microparticles composed of a mixture of carriers represents an innovative approach for lung drug delivery of dry powder. The carriers used can significantly influence the properties of the microparticles, such as size, shape, surface area, hygroscopicity, or aggregation, thus improving the aerosolization of the drugs after inhalation. The properties mentioned above are crucial for effective  pulmonary  therapy. The  combination of carriers of a carbohydrate nature and gelling agents is advantageous for controlled drug release. The experimental work aimed to prepare by spray drying and subsequently evaluate ten batches of microparticles composed of sugar-based carriers (mannitol, maltodextrin, dextran) and gelling polymers (chitosan, chondroitin sulfate) and to select a suitable combination for follow-up experimental work aimed at drug incorporation into the microparticle matrix. The most suitable parameters were exhibited by batches whose aerodynamic diameter was close to 5 µm, particles prepared from a combination of mannitol and dextran, chitosan and chondroitin, or maltodextrin and chondroitin. These batches also showed the highest fine particle fraction value (> 43%). From a processability point of view, the batch with maltodextrin and chondroitin is preferable due to the lower viscosity of the dispersion and the more regular shape of the final microparticles.

Preparation and evaluation of spray-dried inhalable microparticles from carrier mixtures.

The formulation of microparticles composed of a mixture of carriers represents an innovative approach for lung drug delivery of dry powder. The carriers used can significantly influence the properties of the microparticles, such as size, shape, surface area, hygroscopicity, or aggregation, thus improving the aerosolization of the drugs after inhalation. The properties mentioned above are crucial for effective  pulmonary  therapy. The  combination of carriers of a carbohydrate nature and gelling agents is advantageous for controlled drug release. The experimental work aimed to prepare by spray drying and subsequently evaluate ten batches of microparticles composed of sugar-based carriers (mannitol, maltodextrin, dextran) and gelling polymers (chitosan, chondroitin sulfate) and to select a suitable combination for follow-up experimental work aimed at drug incorporation into the microparticle matrix. The most suitable parameters were exhibited by batches whose aerodynamic diameter was close to 5 µm, particles prepared from a combination of mannitol and dextran, chitosan and chondroitin, or maltodextrin and chondroitin. These batches also showed the highest fine particle fraction value (> 43%). From a processability point of view, the batch with maltodextrin and chondroitin is preferable due to the lower viscosity of the dispersion and the more regular shape of the final microparticles.

MiR-214-3p overexpression-triggered chondroitin polymerizing factor (CHPF) inhibition modulates the ferroptosis and metabolism in colon cancer.

Colon cancer is a common cancer with high mortality globally. The role of chondroitin polymerizing factor (CHPF) has been elucidated in various cancers. However, its role and mechanism remain unknown in colon cancer. CHPF expression was examined by GEPIA database, reverse transcription-quantitative polymerase chain reaction and western blot. The relationship between CHPF expression and the clinicopathologic characteristics as well as miR-214-3p level was determined in colon cancer patients. The role and mechanism of CHPF in the growth, ferroptosis, and glycolysis of colon cancer cells were evaluated by cell counting kit-8, biochemical detections, luciferase, and western blot experiments. Additionally, the role of CHPF was explored in xenografted mice. CHPF expression was increased and was related to advanced TNM stage, poor differentiation and shorter overall survival in patients with colon cancer. Knockdown of CHPF inhibited colon cancer cell growth, and downregulated the expression of proteins involving in ferroptosis and glycolysis both in vitro and in vivo. Besides, CHPF silencing increased the levels of ferrous iron and ROS, but decreased glucose uptake, lactate product, and ATP level in vitro. Mechanically, miR-214-3p directly targeted CHPF and negatively regulated its expression. Upregulation of miR-214-3p reduced cell viability, glucose uptake, lactate product, and ATP level, but increased the levels of ferrous iron and ROS, which were reversed by the overexpression of CHPF. Upregulation of CHPF predicted poor prognosis, and miR-214-3p/CHPF axis inhibited growth, downregulated the levels of glycolysis-related indexes, and promoted ferroptosis in colon cancer cells.

Reprogramming Metabolic Flux in Escherichia Coli to Enhance Chondroitin Production.

Reprogramming metabolic flux is a promising approach for constructing efficient microbial cell factories (MCFs) to produce chemicals. However, how to boost the transmission efficiency of metabolic flux is still challenging in complex metabolic pathways. In this study, metabolic flux is systematically reprogrammed by regulating flux size, flux direction, and flux rate to build an efficient MCF for chondroitin production. The ammoniation pool for UDP-GalNAc synthesis and the carbonization pool for UDP-GlcA synthesis are first enlarged to increase flux size for providing enough precursors for chondroitin biosynthesis. Then, the ammoniation pool and the carbonization pool are rematched using molecular valves to shift flux direction from cell growth to chondroitin biosynthesis. Next, the adaptability of polymerization pool with the ammoniation and carbonization pools is fine-tuned by dynamic and static valve-based adapters to accelerate flux rate for polymerizing UDP-GalNAc and UDP-GlcA to produce chondroitin. Finally, the engineered strain E. coli F51 is able to produce 9.2 g L-1 chondroitin in a 5-L bioreactor. This strategy shown here provides a systematical approach for regulating metabolic flux in complex metabolic pathways for efficient biosynthesis of chemicals.

The HNF4A-CHPF pathway promotes proliferation and invasion through interactions with MAD1L1 in glioma.

Chondroitin polymerizing factor (CHPF) is an important glycosyltransferases that participates in the biosynthesis of chondroitin sulfate (CS). Our previous study showed that silencing CHPF expression inhibited glioma cell proliferation in vitro, but the molecular mechanisms by which CHPF contributes to development of glioma have not been characterized. In this study, we found that CHPF was up-regulated in glioma tissues and was positively correlated with malignant clinical pathological characteristics of patients with glioma. Silencing CHPF expression inhibited proliferation, colony formation, migration, and cell cycle of glioma cells. Moreover, silencing CHPF suppressed glioma malignance in vivo. Immunoprecipitation, co-immunoprecipitation, GST pulldown, and liquid chromatography-mass spectrometry (LC-MS/MS) assays were used to verify the interaction between CHPF and Mitotic arrest deficient 1-like 1 (MAD1L1). In addition, Chromatin Immunoprecipitation (ChIP)-PCR analysis showed that HNF4A bound to the CHPF promoter region, which indicated that the transcription factor hepatocyte nuclear factor 4A (HNF4A) could regulate the expression of CHPF in glioma cells.

Causal Effect of Chondroitin, Glucosamine, Vitamin, and Mineral Intake on Kidney Function: A Mendelian Randomization Study.

The causal effects of chondroitin, glucosamine, and vitamin/mineral supplement intake on kidney function remain unknown, despite being commonly used. We conducted a two-sample summary-level Mendelian randomization (MR) analysis to test for causal associations between regular dietary supplement intake and kidney function. Genetic instruments for chondroitin, glucosamine, and vitamin/mineral supplement intake were obtained from a genome-wide association study of European ancestry. Summary statistics for the log-transformed estimated glomerular filtration rate (log-eGFR) were provided by the CKDGen consortium. The multiplicative random-effects inverse-variance weighted method showed that genetically predicted chondroitin and glucosamine intake was causally associated with a lower eGFR (chondroitin, eGFR change beta = -0.113%, standard error (SE) = 0.03%, p-value = 2 × 10-4; glucosamine, eGFR change beta = -0.240%, SE = 0.035%, p-value = 6 × 10-12). However, a genetically predicted vitamin/mineral supplement intake was associated with a higher eGFR (eGFR change beta = 1.426%, SE = 0.136%, p-value = 1 × 10-25). Validation analyses and pleiotropy-robust MR results for chondroitin and vitamin/mineral supplement intake supported the main results. Our MR study suggests a potential causal effect of chondroitin and glucosamine intake on kidney function. Therefore, clinicians should carefully monitor their long-term effects.

Chondroitin/Lactoferrin-dual functionalized pterostilbene-solid lipid nanoparticles as targeted breast cancer therapy.

Breast cancer remains the leading cause of cancer-associated mortality in women. Research investigating novel therapeutic approaches is thus crucial, including phytotherapeutics. Pterostilbene (PTS) is a phytochemical agent with promising efficacy against breast cancer. Poor solubility, low bioavailability and chemical instability are major drawbacks compromising PTS functionality. Herein, novel PTS-loaded solid lipid nanoparticles (PTS-SLNs) were fabricated using the ultrasonication technique. Dual-functionalization with lactoferrin (Lf) and chondroitin-sulfate (CS; CS/Lf/PTS-SLNs) was adopted as active-targeting approach. CS/Lf/PTS-SLNs demonstrated nanoparticle-size (223.42 ± 18.71 nm), low PDI (0.33 ± 0.017), acceptable zeta potential (-11.85 ± 0.07 mV) and controlled release (72.93 ± 2.93% after 24 h). In vitro studies on triple-negative MDA-MB-231 revealed prominent cytotoxicity of CS/Lf/PTS-SLNs (2.63-fold IC50 reduction), higher anti-migratory effect and cellular uptake relative to PTS-solution. The in vivo anti-tumor efficacy in an orthotopic cancer model verified the superiority of CS/Lf/PTS-SLNs; achieving 2.4-fold decrease in tumor growth compared to PTS-solution. On the molecular level, CS/Lf/PTS-SLNs enhanced suppression of VEGF, down-regulated cyclin D1 and upregulated caspase-3 and BAX, compared to PTS-solution. Also, immunohistochemical assay confirmed the higher anti-tumorigenic effect of CS/Lf/PTS-SLNs (5.87-fold decrease in Bcl-2 expression) compared to PTS-solution. Our findings highlight CS/Lf/PTS-SLNs as a promising nanoplatform for phytotherapeutic targeted-breast cancer therapy.

Synergistic delivery of Imatinib through multifunctional nano-crystalline capsules, in response to redox environment for improved breast cancer therapy.

Chondroitin anchored crystalline nano-capsules bearing Imatinib (IMT), and simvastatin (SMV) was developed using Poly (L-lactic acid) (PLLA) by two-step method, i.e., firstly, by synthesizing chondroitin (CSA) anchored simvastatin (SMV) using cystamine as a spacer (SMV-SS-CSA) for disulfide triggered glutathione (GSH) sensitive release and secondly, by developing phenyl boronic ester grafted Pluronic F68 (PEPF) for H2O2 responsive release. By combining these conjugates, we have prepared crystalline nano-capsules (CNs) for preferential targeting of CD44 receptors. The developed CNs were spherical when characterized through SEM, TEM, and AFM for surface morphology, while changes in particle size and crystalline structure were confirmed through Quasi-Elastic light scattering (QELS) and Wide Angle X-ray Scattering (WAXS). The enhanced cellular uptake was noted in chondroitin-modified nano-capsules IMT/SMV-SS-CSA@CNs compared to unmodified nano-capsules IMT+SMV@CNs. IMT/SMV-SS-CSA@CNs displayed significantly higher G2/M phase arrest (76.9%) than unmodified nano-capsules. The prototype formulation (IMT/SMV-SS-CSA@CNs) showed an overall improved pharmacokinetic profile in terms of both half-life and AUC0-α. When tested in the 4T1 subcutaneously injected tumor-bearing Balb/c mice model, the tumor growth inhibition rate of IMT/SMV-SS-CSA@CNs was significantly higher (91%) than the IMT+SMV combination. Overall, the findings suggest that the proposed dual responsive chondroitin-modified drug delivery could have a step forward in achieving spatial and temporal targeting at the tumor site.

Glucosamine and Chondroitin Use and Mortality Among Adults in the United States from 1999 to 2014.

Introduction: Glucosamine and chondroitin are supplements that are often, but not always, used in combination for arthritis and joint pain. Multiple studies have suggested that glucosamine and chondroitin may be associated with reduced risk of several diseases, as well as all-cause, cancer- and respiratory disease-specific mortality. Methods: Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) were used to further evaluate the association between glucosamine and chondroitin with mortality. Participants include 38,021 adults, ages 20+ years and older, who completed the detailed NHANES between 1999 and 2014. Participants were followed for death through linkage with the National Death Index through the end of 2015, over which time 4905 deaths occurred. Adjusted hazard ratios (HRs) for overall and cause-specific mortality were estimated using Cox regression models. Results: Despite glucosamine and chondroitin use appearing to be inversely associated with mortality in the minimally adjusted models, no association was observed in multivariable models (glucosamine: HR = 1.02; 95% confidence interval [CI]: 0.86-1.21, chondroitin: HR = 1.04, 95% CI: 0.87-1.25). No association with cancer mortality or other mortality rate was observed after multivariable adjustment. There was a suggestive, nonsignificant inverse association for cardiovascular-specific mortality (glucosamine HR = 0.72; 95% CI: 0.46-1.15, chondroitin: HR = 0.76; 95% CI: 0.47-1.21). Conclusion: The lack of significant relationship between glucosamine and chondroitin use and all-cause or cause-specific mortality after adjusting extensively for multiple covariates in this nationally representative adult population was in contrast to prior literature. Given the limited power to explore the cause-specific mortality, future well-powered studies will be needed to better understand the potential association with cardiovascular-specific mortality.

Interaction of Chondroitin and Hyaluronan Glycosaminoglycans with Surfaces of Carboxylated Carbon Nanotubes Studied Using Molecular Dynamics Simulations.

Interaction of ß-D-glucopyranuronic acid (GlcA), N-acetyl-ß-D-glucosamine (GlcNAc), N-acetyl-ß-D-galactosamine (GalNAc) and two natural decameric glycosaminoglycans, hyaluronic acid (HA) and Chondroitin (Ch) with carboxylated carbon nanotubes, were studied using molecular dynamics simulations in a condensed phase. The force field used for carbohydrates was the GLYCAM-06j version, while functionalized carbon nanotubes (fCNT) were described using version two of the general amber force field. We found a series of significant differences in carbohydrate-fCNT adsorption strength depending on the monosaccharide molecule and protonation state of surface carboxyl groups. GlcNAc and GalNAc reveal a strong adsorption on fCNT with deprotonated carboxyl groups, and a slightly weaker adsorption on the fCNT with protonated carboxyl groups. On the contrary, GlcA weakly adsorbs on fCNT. The change in protonation state of surface carboxyl groups leads to the reversal orientation of GlcNAc and GalNAc in reference to the fCNT surface, while GlcA is not sensitive to that factor. Adsorption of decameric oligomers on the surface of fCNT weakens with the increasing number of monosaccharide units. Chondroitin adsorbs weaker than hyaluronic acid and incorporation of four Ch molecules leads to partial detachment of them from the fCNT surface. The glycan-fCNT interactions are strong enough to alter the conformation of carbohydrate backbone; the corresponding conformational changes act toward a more intensive contact of glycan with the fCNT surface. Structural and energetic features of the adsorption process suggest the CH-π interaction-driven mechanism.

Immunochemical Detection and Glycosaminoglycan Disaccharide-Based Characterization of Chondroitin Sulfate Proteoglycans.

Chondroitin sulfate proteoglycans (CSPGs) are polyanionic extra/pericellular matrix macromolecules that surround almost all cell types and create microenvironmental niches to support miscellaneous cellular events. In general, the multifunctional properties of CSPGs are attributable to the structural divergence of the CS glycosaminoglycan (GAG) moieties. Because the expression profiles of the GAG chains of CSPGs change with developmental stage, aging, and disease progression, characterization of the GAG chains is essential to understand the functional roles of CSPGs. This chapter describes the basic protocols for GAG moiety-based immunochemical detection of CSPGs in biological samples in conjunction with CS disaccharide composition analysis.

Role of Glucosamine and Chondroitin in the Prevention of Cancer: A Meta-Analysis.

The anti-inflammatory properties of glucosamine and chondroitin suggest that they may have potential effects in cancer prevention. We performed this meta-analysis to assess the protective function of glucosamine and/or chondroitin intake against cancer risk. We searched the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) databases. The odds ratio (OR), corresponding to the 95% confidence interval (95% CI), was used to assess the association between chondroitin and/or glucosamine intake and cancer risk. Thirteen studies met the inclusion criteria, with 1,690,918 participants and 55,045 cancer cases. Overall, chondroitin and/or glucosamine intake was associated with a lower risk of colorectal cancer (OR = 0.91, 95% CI, 0.87-0.94) and lung cancer (OR = 0.84, 95% CI, 0.79-0.89). Subgroup analysis supported the protective effect of different SYSADOAs (chondroitin and/or glucosamine) intake. However, the protective effect was not observed in the only chondroitin intake group and in the NSAIDs group. Our meta-analysis found that the intake of glucosamine and/or chondroitin decreased the risk of colorectal and lung cancers. Moreover, NSAIDs use may have a synergistic protective effect.

Efficacy and safety of the combination of glucosamine and chondroitin for knee osteoarthritis: a systematic review and meta-analysis.

AIMS: Though glucosamine and chondroitin have become common practices for treating knee osteoarthritis, the clinical value of these two drugs in combination are still questionable. To evaluate the efficacy and safety of the combination of glucosamine (GS) and chondroitin (CS) in knee osteoarthritis (KOA) treatment. METHODS: We searched electronic databases, including PubMed, Embase, Web of Science, SCOPUS, The Cochrane Central Register of Controlled Trials (CENTRAL), OVID, Chinese Clinical Trial Registry (ChiCTR), CBM, CNKI, WanFang and VIP from their inception to August 20, 2020, for literature concerning the combination of glucosamine and chondroitin in knee osteoarthritis treatment. The Cochrane Collaboration's tool for assessing risk of bias and Jadad scale were used to evaluate the risk of bias and quality of literature. The meta-analysis was performed using Review Manager 5.3 software. RESULTS: Eight randomized controlled trials (RCTs) were included, including 7 studies in English and 1 study in Chinese. While the number of included papers was quite limited, the number of participants was decent, and quality appraisal result is acceptable. The total number of patients was 3793, with 1067 patients receiving a combination of glucosamine and chondroitin and 2726 patients receiving other treatments. The meta-analysis results revealed the following: (1) Regarding the total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, compared with the placebo group, the combination group showed a statistically significant advantage [MD = - 12.04 (- 22.33 ~ - 1.75); P = 0.02], while the other groups showed no significance. (2) Regarding the VAS score, none of the comparisons showed significance. (3) In the secondary outcomes, except the comparison of JSN between the combination and placebo groups (MD = - 0.09 (- 0.18 ~ - 0.00); P = 0.04) and the comparison of the WOMAC stiffness score between the combination and CS groups [MD = - 4.70 (- 8.57 ~ - 0.83); P = 0.02], none of the comparisons showed a significant difference. (4)Safety analysis results show that none of the comparisons have significant differences. CONCLUSION: Our study confirmed that the combination of glucosamine and chondroitin is effective and superior to other treatments in knee osteoarthritis to a certain extent. It is worthwhile to popularize and apply the combination in KOA treatment considering the point of effect, tolerability and economic costs. Additionally, regarding the limited number of studies and uneven trial quality, more high-quality trials are required to investigate the accurate clinical advantages of the combination. PROSPERO REGISTRATION ID: CRD42020202093.

Chondroitin sulfate is not digested at all in the mouse small intestine but may suppress interleukin 6 expression induced by tumor necrosis factor-α.

Salmon nasal cartilage proteoglycan (PG) was orally administered to mice. The PG digest was recovered from the small intestine, and its sugar chain size and unsaturated disaccharide content were examined. The elution position of the PG digest following Sepharose CL-4B chromatography was consistent with that of actinase-digested PG prior to administration. The PG digest was incubated with chondroitinase ABC, which resulted in the elution pattern of the unsaturated disaccharides being identical to that of the degraded product of actinase-digested PG. The core protein of PG was digested in the mouse small intestine, but chondroitin sulfate, which is the sugar chain of PG, was not degraded at all. Then, the effects of chondroitin 4- and 6-sulfates on human colon cancer cells were examined. These chondroitin sulfates were found to suppress the expression of interleukin-6 induced by TNF-α. Overall, the chondroitin sulfate chain may act on the intestinal epithelium and suppress inflammation of the intestinal tract.

Highly sensitive quantification of bacterial chondroitin in a culture based on ELISA techniques.

Some bacteria produce non-sulfated chondroitin (CH). Accurate, rapid, and high throughput methods to quantify CH in fermented cultures helps to improve microbial breeding and fermentation conditions efficiently. In this study, highly sensitive methods to quantify bacterial CH were developed based on ELISA techniques. An assay using an anti-K4 antiserum successfully determined the concentration of fructosylated CH in the range from 9 to 800 ng/mL. The method also enabled the determination of CH concentration exceeding 9 µg/mL. To improve the assay sensitivity for CH, hyaluronan (HA) binding protein (HABP) was applied instead of a capture antibody. HABP was bound to CH, but not to chemically desulfated chondroitin sulfate or fructosylated CH. The quantification limit of CH was 18 µg/mL in the HA assay using HABP. Replacing the HA-coated microplate with a CH-coated microplate increased the sensitivity >1000 times (assay range = 14 to 1000 ng/mL). Pretreatment with hyaluronidase enabled us to accurately quantify CH in samples mixed with HA.

[A multicenter cross-sectional study of quality of life and nonsurgical treatment in patients with knee osteoarthritis].

Objective: To explore the influencing factors of health-related quality of life (HRQoL) in patients with knee osteoarthritis, and to analyze the non-surgical treatment of knee osteoarthritis. Methods: Demographic variables, treatment modalities, imaging data, and 12-item short form health survey (SF-12) scores of patients with knee osteoarthritis in orthopedic outpatient departments of five hospitals in Beijing from December 2017 to November 2018 were collected to analyze influencing factors of HRQoL and non-surgical treatment. Results: A total of 2 034 patients were included. There were 530 males (26.1%) and 1 504 females (73.9%), with a mean age of (59.17±10.22) years. In terms of physical quality of life, female patients with knee osteoarthritis had lower physical components summary (PCS) compared with male patients (ß=-0.521, P=0.036); patients aged ≥64 years had lower PCS than those aged<55 years (ß=-0.636, P=0.026). Patients with an education of more than 12 years had higher PCS than those with less than 10 years (ß=1.063, P<0.001). Compared to patients with mild clinical symptoms, the PCS of patients with moderate clinical symptoms was lower (ß=-0.860, P=0.002), while the PCS of those with severe clinical symptoms was much lower (ß=-1.126, P<0.001). Patients treated with combination therapy had higher PCS than untreated patients (ß=0.731, P=0.005). In terms of mental quality of life, compared to patients engaged in sedentary work, the mental components summary (MCS) of patients engaged in mild manual labor jobs was lower (ß=-0.712, P=0.015); Compared to patients with a Charson comorbidity index of 0, patients with a Charlson comorbidity index ≥ 2 had lower MCS (ß=-1.183, P=0.007). In the past 12 months, 648 (31.9%), 143 (7.0%), 406 (20.0%), 680 (33.4%), 343 (16.9%), 681 (33.5%), 170 (8.4%) patients had used non-steroid anti-inflammatory drugs (NSAIDs), acetaminophen, glucosamine/chondroitin formulations, physical therapy, articular cavity puncture injection, traditional Chinese medicine treatment and exercise therapy, respectively. Total of 451 patients (22.2%) received monotherapy and 889 patients (43.7%) received combination therapy. Conclusions: The major non-surgical treatment methods for patients with knee osteoarthritis in Beijing are NSAIDs, physiotherapy and traditional Chinese medicine. Combination therapy is used more frequently than monotherapy. Physical quality of life is related to gender, age, education, severity of symptoms and treatment, while mental quality of life is related to occupational labor and comorbidities.

A 2022 Systematic Review and Meta-Analysis of Enriched Therapeutic Diets and Nutraceuticals in Canine and Feline Osteoarthritis.

With osteoarthritis being the most common degenerative disease in pet animals, a very broad panel of natural health products is available on the market for its management. The aim of this systematic review and meta-analysis, registered on PROSPERO (CRD42021279368), was to test for the evidence of clinical analgesia efficacy of fortified foods and nutraceuticals administered in dogs and cats affected by osteoarthritis. In four electronic bibliographic databases, 1578 publications were retrieved plus 20 additional publications from internal sources. Fifty-seven articles were included, comprising 72 trials divided into nine different categories of natural health compound. The efficacy assessment, associated to the level of quality of each trial, presented an evident clinical analgesic efficacy for omega-3-enriched diets, omega-3 supplements and cannabidiol (to a lesser degree). Our analyses showed a weak efficacy of collagen and a very marked non-effect of chondroitin-glucosamine nutraceuticals, which leads us to recommend that the latter products should no longer be recommended for pain management in canine and feline osteoarthritis.

Biosynthesis of non-sulfated high-molecular-weight glycosaminoglycans and specific-sized oligosaccharides.

Non-sulfated forms of glycosaminoglycans (NSGAGs) including hyaluronan, chondroitin and heparosan with high-molecular-weight (HMW) are extensively used biomaterials, while NSGAGs oligosaccharides display strong bioactivities. However, microbial production of HMW-NSGAGs and oligosaccharides with specific size are always challenging. Here, a membrane shield strategy was developed to produce HMW-NSGAGs by recruiting type II NSGAG synthases in Corynebacterium glutamicum. By enhancing precursor supplies and reinforcing cell membrane, the MWs of hyaluronan, heparosan and chondroitin reached 4100 kDa, 3000 kDa and 2400 kDa, respectively. In parallel, a synchronized depolymerization-polymerization strategy was developed by co-expressing NSGAGs synthases and lyases. With cell membrane as a filter, we achieved the direct biosynthesis of NSGAGs tetrasaccharides and disaccharides. The titers of chondroitin, hyaluronan and heparosan tetrasaccharides and disaccharides reached 10.9 g L-1, 12.1 g L-1 and 5.8 g L-1, respectively. The strategies developed here should also be applicable to the biosynthesis of other polysaccharides.

Clinical Efficacy and Safety of Chondroitin Combined with Glucosamine in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

Objective: This analysis was aimed at providing evidence-based medicine basis for systematic evaluation of chondroitin combined with glucosamine in the treatment of knee osteoarthritis. Methods: The randomized controlled trials (RCTs) of chondroitin combined with glucosamine in the treatment of knee osteoarthritis (KOA) were searched in PubMed, EMBASE, ScienceDirect, Cochrane Library, China Knowledge Network Database (CNKI), China VIP Database, Wanfang Database, and China Biomedical Literature Database (CBM) online database. The retrieval time ranges from the database creation to the present. Two investigators gathered the information individually. The risk of bias was assessed using the criteria of the Cochrane back review group. RevMan5.4 statistical software analyzed the selected data. Results: A total of 6 RCT articles were obtained. Overall, 764 samples were evaluated by meta-analysis. The clinical efficacy of chondroitin combined with glucosamine was significantly better than that of routine treatment by meta-analysis. The confidence interval of 95% was (4.86, 17.08) (Z = 6.89, P < 0.00001). The scores of joint pain, tenderness, swelling, and dysfunction in patients with knee osteoarthritis treated with chondroitin combined with glucosamine were significantly lower than those treated with routine treatment. There was no significant difference in the incidence of adverse reactions between chondroitin combined with glucosamine and single treatment of KOA. Due to the small number of documents included in the analysis, it is not suitable to make a funnel chart, but there may be some publication deviation in the analysis. Conclusion: Chondroitin combined with glucosamine is more effective than chondroitin or glucosamine alone in the treatment of KOA and deserves clinical promotion. However, this conclusion still needs to be supported by multicenter, high-quality, double-blind, large-sample randomized controlled clinical trials due to the limitations of the six trials included.