Collagen Biosynthesis Research Articles

Amaranthus cruentus L. Seed Oil Counteracts UVA-Radiation-Induced Inhibition of Collagen Biosynthesis and Wound Healing in Human Skin Fibroblasts.

The effect of Amaranthus cruentus L. seed oil (AmO) on collagen biosynthesis and wound healing was studied in cultured human dermal fibroblasts exposed to UVA radiation. It was found that UVA radiation inhibited collagen biosynthesis, prolidase activity, and expression of the β1-integrin receptor, and phosphorylated ERK1/2 and TGF-β, while increasing the expression of p38 kinase. The AmO at 0.05-0.15% counteracted the above effects induced by UVA radiation in fibroblasts. UVA radiation also induced the expression and nuclear translocation of the pro-inflammatory NF-κB factor and enhanced the COX-2 expression. AmO effectively suppressed the expression of these pro-inflammatory factors induced by UVA radiation. Expressions of β1 integrin and IGF-I receptors were decreased in the fibroblasts exposed to UVA radiation, while AmO counteracted the effects. Furthermore, AmO stimulated the fibroblast's migration in a wound healing model, thus facilitating the repair process following exposure of fibroblasts to UVA radiation. These data suggest the potential of AmO to counteract UVA-induced skin damage.

Transcriptional Profiling of Muscle in Females With Distal Radius Fracture and Functional Sarcopenia.

Skeletal muscle and bone interact with each other in mechanical and biochemical ways. This study aimed to investigate the molecular mechanisms of interaction between muscle and bone by analyzing the transcriptional profiles of total RNA from the muscle tissue of females with distal radius fractures. A total of 30 female participants (mean age 71.1 ± 8.9 years) with distal radius fractures were recruited. Participants were categorized into 2 groups: the NORM group consisted of participants with T score of the areal bone mineral density (aBMD) of the femoral neck higher than -1.0, handgrip strength greater than 18kg, and gait speed faster than 1.0 m/s (n = 10). Otherwise, participants with T score of the aBMD of the femoral neck equal to or less than -1.0, handgrip strength lower than 18kg, and gait speed slower than 1.0 m/s (n = 20) were categorized into EXP group. Pronator quadratus muscle samples were obtained from all participants. Total RNA was extracted from frozen muscle samples and sequenced. The gene ontology analysis demonstrated that the potential interactions between attached muscle function and the density of the associated bone would be linked with collagen biosynthetic activity and maintenance of extracellular matrix structures. The analysis of the pathway, network, and protein class exhibited that integrin signaling, inflammatory reactions, matrix metalloproteinase (MMP) activity, and extracellular matrix protein structure had possible associations with the molecular background of muscle-bone interaction. Through integrin signaling, MMP activity, inflammatory reactions, and collagen biosynthesis, muscle and bone may mutually interact with one another.

The role of P3H family in cancer: implications for prognosis, tumor microenvironment and drug sensitivity.

Prolyl 3-hydroxylases (P3H) are crucial enzymes in collagen biosynthesis and are known to be involved in a variety of physiological processes. However, their specific roles in cancer progression, modulation of the tumor microenvironment (TME), and impact on patient prognosis remain areas that require further investigation. The investigation involved a comprehensive analysis of expression profiles and clinical data obtained from the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases. This included the assessment of genetic variation, gene expression, and the prognostic significance of P3H family genes. P3H scores were calculated using various databases and R-based tools, followed by correlation analyses with the TME, immune cell infiltration, drug sensitivity and immunotherapy.Variations in P3H gene expression patterns were observed across different tumor types and prognoses, suggesting that most genes within the family were risk factors, especially P3H1 and P3H4. The P3H score was associated with immune infiltration and drug resistance. Notably, individuals with elevated expression of P3H2, P3H3, and CRTAP exhibited higher resistance to multiple anti-tumor drugs. P3H family proteins play diverse roles in cancer progression, significantly impacting patient prognosis and the effectiveness of immunotherapy. The P3H score, identified as a potential biomarker for evaluating TME, holds promise in guiding precision medicine strategies.

KLF6 activates Sp1-mediated prolidase transcription during TGF-β1 signaling

Prolidase (PEPD) is the only hydrolase that cleaves the dipeptides containing C-terminal proline or hydroxyproline- the rate-limiting step in collagen biosynthesis. However, the molecular regulation of prolidase expression remains largely unknown. In this study, we have identified overlapping binding sites for the transcription factors- Krüppel‐like factor 6 (KLF6) and Specificity protein 1 (Sp1) in the PEPD promoter and demonstrate that KLF6/Sp1 transcriptionally regulate prolidase expression. By cloning the PEPD promoter into a luciferase reporter and through site-directed deletion, we pinpointed the minimal sequences required for KLF6 and Sp1-mediated PEPD promoter-driven transcription. Interestingly, Sp1 inhibition abrogated KLF6-mediated PEPD promoter activity, suggesting that Sp1 is required for the basal expression of prolidase. We further studied the regulation of PEPD by KLF6 and Sp1 during transforming growth factor β1 (TGF-β1) signaling, since both KLF6 and Sp1 are key players in TGF-β1 mediated collagen biosynthesis. Mouse and human fibroblasts exposed to TGF-β1 resulted in the induction of PEPD transcription and prolidase expression. Inhibition of TGF-β1 signaling abrogated PEPD promoter-driven transcriptional activity of KLF6 and Sp1. Knock-down of KLF6 as well as Sp1 inhibition also reduced prolidase expression. Chromatin immunoprecipitation assay supported direct binding of KLF6 and Sp1 to the PEPD promoter and this binding was enriched by TGF-β1 treatment. Finally, immunofluorescence studies showed that KLF6 co-operates with Sp1 in the nucleus to activate prolidase expression and enhance collagen biosynthesis. Collectively, our results identify functional elements of the PEPD promoter for KLF6 and Sp1-mediated transcriptional activation and describe the molecular mechanism of prolidase expression.

Host-microbiota interactions contributing to the heterogeneous tumor microenvironment in colorectal cancer.

Colorectal cancer (CRC) exhibits pronounced heterogeneity and is categorized into four widely accepted consensus molecular subtypes (CMSs) with unique tumor microenvironments (TMEs). However, the intricate landscape of the microbiota and host-microbiota interactions within these TMEs remains elusive. Using RNA-sequencing data from The Cancer Genome Atlas, we analyzed the host transcriptomes and intratumoral microbiome profiles of CRC samples. Distinct host genes and microbial genera were identified among the CMSs. Immune microenvironments were evaluated using CIBERSORTx and ESTIMATE, and microbial coabundance patterns were assessed with FastSpar. Through LASSO penalized regression, we explored host-microbiota associations for each CMS. Our analysis revealed distinct host gene signatures within the CMSs, which encompassed ferroptosis-related genes and specific immune microenvironments. Moreover, we identified 293, 153, 66, and 109 intratumoral microbial genera with differential abundance, and host-microbiota associations contributed to distinct TMEs, characterized by 829, 1,270, 634, and 1,882 robust gene-microbe associations for each CMS in CMS1-CMS4, respectively. CMS1 featured inflammation-related HSF1 activation and gene interactions within the endothelin pathway and Flammeovirga. Integrin-related genes displayed positive correlations with Sutterella in CMS2, whereas CMS3 spotlighted microbial associations with biosynthetic and metabolic pathways. In CMS4, genes involved in collagen biosynthesis showed positive associations with Sutterella, contributing to disruptions in homeostasis. Notably, immune-rich subtypes exhibited pronounced ferroptosis dysregulation, potentially linked to tissue microbial colonization. This comprehensive investigation delineates the diverse landscapes of the TME within each CMS, incorporating host genes, intratumoral microbiota, and their complex interactions. These findings shed light on previously uncharted mechanisms underpinning CRC heterogeneity and suggest potential therapeutic targets.NEW & NOTEWORTHY This study determined the following: 1) providing a comprehensive landscape of consensus molecular subtype (CMS)-specific tumor microenvironments (TMEs); 2) constructing CMS-specific networks, including host genes, intratumoral microbiota, and enriched pathways, analyzing their associations to uncover unique patterns that demonstrate the intricate interplay within the TME; and 3) revealing a connection between immune-rich subtypes and ferroptosis activation, suggesting a potential regulatory role of the microbiota in ferroptosis dysregulation of the colorectal cancer TME.

Injectable Microparticle-containing hydrogel with controlled release of bioactive molecules for facial rejuvenation

The skin is the largest organ and a crucial barrier for protection against various intrinsic and extrinsic factors. As we age, the skin's components become more vulnerable to damage, forming wrinkles. Among different procedures, hyaluronic acid-based hydrogel has been extensively utilized for skin regeneration and reducing wrinkles. However, it has limitations like low retention and weak mechanical properties. In this study, we suggested the poly(l-lactic acid) (PLLA) microparticles containing alkaline magnesium hydroxide and nitric oxide-generating zinc oxide and rejuvenative hyaluronic acid (HA) hydrogels including these functional microparticles and asiaticoside, creating a novel delivery system for skin rejuvenation and regeneration. The fabricated rejuvenative hydrogels have exhibited enhanced biocompatibility, pH neutralization, reactive oxygen species scavenging, collagen biosynthesis, and angiogenesis capabilities in vitro and in vivo. Additionally, an excellent volume retention ability was demonstrated due to the numerous hydrogen bonds that formed between hyaluronic acid and asiaticoside. Overall, our advanced injectable hydrogel containing functional microparticles, with controlled release of bioactive molecules, has a significant potential for enhancing the regeneration and rejuvenation of the skin.

Therapeutic potential of Zataria multiflora: A narrative review of current evidence

Zataria multiflora Boiss is a perennial plant with a wide spectrum of biological and pharmacological activities including antidiabetic, anti-nociceptive, anti-asthmatic, anti-fever, anti-spastic, anti-oxidative, anti-inflammatory, and antimicrobial properties. This paper reviews the therapeutic effects of Zataria multiflora based on recent reports. The relevant reports were extracted by checking the electronic databases including PubMed, Scopus, Web of Science, and Google Scholar from the beginning of 2010 until the end of May 2023. The neuroprotective effects of Zataria multiflora can be attributed to inhibition of acetylcholinesterase, enhancement of brain-derived neurotrophic factor, and alleviation of brain oxidative damage. Zataria multiflora also exerts its protective effects on the respiratory system, liver, and kidney by reducing the level of inflammatory cytokines, scavenging the free radicals, and augmenting the antioxidant enzymes. Additionally, Zataria multiflora accelerates wound healing via upregulating transforming growth factor-β, insulin-like growth factor 1, fibroblast growth factor 2, and vascular endothelial growth factor, and inducing angiogenesis and collagen biosynthesis. Overall, the protective impacts of Zataria multiflora on different organs are mainly attributed to its antioxidant and anti-inflammatory properties.

Uterine Collagen Cross-Linking: Biology, Role in Disorders, and Therapeutic Implications.

Collagen is an essential constituent of the uterine extracellular matrix that provides biomechanical strength, resilience, structural integrity, and the tensile properties necessary for the normal functioning of the uterus. Cross-linking is a fundamental step in collagen biosynthesis and is critical for its normal biophysical properties. This step occurs enzymatically via lysyl oxidase (LOX) or non-enzymatically with the production of advanced glycation end-products (AGEs). Cross-links found in uterine tissue include the reducible dehydro-dihydroxylysinonorleucine (deH-DHLNL), dehydro-hydroxylysinonorleucine (deH-HLNL), and histidinohydroxymerodesmosine (HHMD); and the non-reducible pyridinoline (PYD), deoxy-pyridinoline (DPD); and a trace of pentosidine (PEN). Collagen cross-links are instrumental for uterine tissue integrity and the continuation of a healthy pregnancy. Decreased cervical cross-link density is observed in preterm birth, whereas increased tissue stiffness caused by increased cross-link density is a pathogenic feature of uterine fibroids. AGEs disrupt embryo development, decidualization, implantation, and trophoblast invasion. Uterine collagen cross-linking regulators include steroid hormones, such as progesterone and estrogen, prostaglandins, proteoglycans, metalloproteinases, lysyl oxidases, nitric oxide, nicotine, and vitamin D. Thus, uterine collagen cross-linking presents an opportunity to design therapeutic targets and warrants further investigation in common uterine disorders, such as uterine fibroids, cervical insufficiency, preterm birth, dystocia, endometriosis, and adenomyosis.

Assessment of in vitro anti-skin aging activities of Phyllanthus indofischeri Bennet extracts for dermatological and aesthetic applications

Giant Indian Gooseberry (GIG) or Phyllanthus indofischeri Bennet are commercially cultivated and commonly used herbs in Traditional medicine, especially in Thailand. The aim of this study was to assess the potential of the GIG extracts in anti-aging activities to be a dermatological application. The juice, meat residues, and seeds of GIG collected from Sra Kaeo Province, Thailand, were extracted by the Boiling method (B) and the Maceration process (M) by using 95% ethanol as a solvent. The GIG extracts gave the total phenolic, total flavonoid contents and quercetin contents, as well as exhibited anti-oxidative activities. The GIG-R-B extract inhibited tyrosinase activity and had the highest anti-melanogenesis activity on B16F10 cells at 31.63 ± 0.70%. The GIG-S-B, GIG-S-M, and GIG-R-M extracts demonstrated the highest collagen biosynthesis, which was comparable to vitamin C (p < 0.05), whereas the GIG-R-B extracts gave the highest stimulation of anti-aging genes (SIRT1 and FOXO1). All extracts at the concentration of 0.1 mg/mL showed no cytotoxicity on human skin fibroblasts. Therefore, the GIG-S-B extract was discovered to be a promising natural anti-aging agent for dermatological health and aesthetic applications that can be further developed in cosmetic, functional food and food supplement industries.

Common Beans as a Source of Amino Acids and Cofactors for Collagen Biosynthesis.

Common beans (Phaseolus vulgaris L.) are widely consumed in diets all over the world and have a significant impact on human health. Proteins, vitamins, minerals, phytochemicals, and other micro- and macronutrients are abundant in these legumes. On the other hand, collagens, the most important constituent of extracellular matrices, account for approximately 25-30 percent of the overall total protein composition within the human body. Hence, the presence of amino acids and other dietary components, including glycine, proline, and lysine, which are constituents of the primary structure of the protein, is required for collagen formation. In this particular context, protein quality is associated with the availability of macronutrients such as the essential amino acid lysine, which can be acquired from meals containing beans. Lysine plays a critical role in the process of post-translational modifications facilitated with enzymes lysyl hydroxylase and lysyl oxidase, which are directly involved in the synthesis and maturation of collagens. Furthermore, collagen biogenesis is influenced by the cellular redox state, which includes important minerals and bioactive chemicals such as iron, copper, and certain quinone cofactors. This study provides a novel perspective on the significant macro- and micronutrients present in Phaseolus vulgaris L., as well as explores the potential application of amino acids and cofactors derived from this legume in the production of collagens and bioavailability. The utilization of macro- and micronutrients obtained from Phaseolus vulgaris L. as a protein source, minerals, and natural bioactive compounds could optimize the capacity to promote the development and durability of collagen macromolecules within the human body.

Role of Pericytes in Cardiomyopathy-Associated Myocardial Infarction Revealed by Multiple Single-Cell Sequencing Analysis.

Acute myocardial infarction (AMI) is one of the leading causes of cardiovascular death worldwide. AMI with cardiomyopathy is accompanied by a poor long-term prognosis. However, limited studies have focused on the mechanism of cardiomyopathy associated with AMI. Pericytes are important to the microvascular function in the heart, yet little attention has been paid to their function in myocardial infarction until now. In this study, we integrated single-cell data from individuals with cardiomyopathy and myocardial infarction (MI) GWAS data to reveal the potential function of pericytes in cardiomyopathy-associated MI. We found that pericytes were concentrated in the left atrium and left ventricle tissues. DLC1/GUCY1A2/EGFLAM were the top three uniquely expressed genes in pericytes (p < 0.05). The marker genes of pericytes were enriched in renin secretion, vascular smooth muscle contraction, gap junction, purine metabolism, and diabetic cardiomyopathy pathways (p < 0.05). Among these pathways, the renin secretion and purine metabolism pathways were also found in the process of MI. In cardiomyopathy patients, the biosynthesis of collagen, modulating enzymes, and collagen formation were uniquely negatively regulated in pericytes compared to other cell types (p < 0.05). COL4A2/COL4A1/SMAD3 were the hub genes in pericyte function involved in cardiomyopathy and AMI. In conclusion, this study provides new evidence about the importance of pericytes in the pathogenesis of cardiomyopathy-associated MI. DLC1/GUCY1A2/EGFLAM were highly expressed in pericytes. The hub genes COL4A2/COL4A1/SMAD3 may be potential research targets for cardiomyopathy-associated MI.

Mitochondrial glutamate transporter SLC25A22 uni-directionally export glutamate for metabolic rewiring in radioresistant glioblastoma

Glioblastoma Multiforme (GBM) is a malignant primary brain tumor. Radiotherapy, one of the standard treatments for GBM patients, could induce GBM radioresistance via rewiring cellular metabolism. However, the precise mechanism attributing to GBM radioresistance or targeting strategies to overcome GBM radioresistance are lacking. Here, we demonstrate that SLC25A22, a mitochondrial bi-directional glutamate transporter, is upregulated and showed uni-directionality from mitochondria to cytosol in radioresistant GBM cells, resulting in accumulating cytosolic glutamate. However, mitochondrial glutaminolysis-mediated TCA cycle metabolites and OCR are maintained constantly. The accumulated cytosolic glutamate enhances the glutathione (GSH) production and proline synthesis in radioresistant GBM cells. Increased GSH protects cells against ionizing radiation (IR)-induced reactive oxygen species (ROS) whereas increased proline, a rate-limiting substrate for collagen biosynthesis, induces extracellular matrix (ECM) remodeling, leading to GBM invasive phenotypes. Finally, we discover that genetic inhibition of SLC25A22 using miR-184 mimic decreases GBM radioresistance and aggressiveness both in vitro and in vivo. Collectively, our study suggests that SLC25A22 upregulation confers GBM radioresistance by rewiring glutamate metabolism, and SLC25A22 could be a significant therapeutic target to overcome GBM radioresistance.

Evaluating osteogenic effects associated with the incorporation of ascorbic acid in mineralized collagen scaffolds.

Current treatments for craniomaxillofacial (CMF) defects motivate the design of instructive biomaterials that can promote osteogenic healing of complex bone defects. We report methods to promote in vitro osteogenesis of human mesenchymal stem cells (hMSCs) within a model mineralized collagen scaffold via the incorporation of ascorbic acid (vitamin C), a key factor in collagen biosynthesis and bone mineralization. An addition of 5 w/v% ascorbic acid into the base mineralized collagen scaffold significantly changes key morphology characteristics including porosity, macrostructure, and microstructure. This modification promotes hMSC metabolic activity, ALP activity, and hMSC-mediated deposition of calcium and phosphorous. Additionally, the incorporation of ascorbic acid influences osteogenic gene expression (BMP-2, RUNX2, COL1A2) and delays the expression of genes associated with osteoclast activity and bone resorption (OPN, CTSK), though it reduces the secretion of OPG. Together, these findings highlight ascorbic acid as a relevant component for mineralized collagen scaffold design to promote osteogenic differentiation and new bone formation for improved CMF outcomes.

Multi-Omics Profiling of Human Endothelial Cells from the Coronary Artery and Internal Thoracic Artery Reveals Molecular but Not Functional Heterogeneity.

Major adverse cardiovascular events occurring upon coronary artery bypass graft surgery are typically accompanied by endothelial dysfunction. Total arterial revascularisation, which employs both left and right internal thoracic arteries instead of the saphenous vein to create a bypass, is associated with better mid- and long-term outcomes. We suggested that molecular profiles of human coronary artery endothelial cells (HCAECs) and human internal mammary artery endothelial cells (HITAECs) are coherent in terms of transcriptomic and proteomic signatures, which were then investigated by RNA sequencing and ultra-high performance liquid chromatography-mass spectrometry, respectively. Both HCAECs and HITAECs overexpressed molecules responsible for the synthesis of extracellular matrix (ECM) components, basement membrane assembly, cell-ECM adhesion, organisation of intercellular junctions, and secretion of extracellular vesicles. HCAECs were characterised by higher enrichment with molecular signatures of basement membrane construction, collagen biosynthesis and folding, and formation of intercellular junctions, whilst HITAECs were notable for augmented pro-inflammatory signaling, intensive synthesis of proteins and nitrogen compounds, and enhanced ribosome biogenesis. Despite HCAECs and HITAECs showing a certain degree of molecular heterogeneity, no specific markers at the protein level have been identified. Coherence of differentially expressed molecular categories in HCAECs and HITAECs suggests synergistic interactions between these ECs in a bypass surgery scenario.

Amnion responses to intrauterine inflammation and effects of inhibition of TNF signaling in preterm Rhesus macaque

Intrauterine infection/inflammation (IUI) is a frequent complication of pregnancy leading to preterm labor and fetal inflammation. How inflammation is modulated at the maternal-fetal interface is unresolved. We compared transcriptomics of amnion (a fetal tissue in contact with amniotic fluid) in a preterm Rhesus macaque model of IUI induced by lipopolysaccharide with human cohorts of chorioamnionitis. Bulk RNA sequencing (RNA-seq) amnion transcriptomic profiles were remarkably similar in both Rhesus and human subjects and revealed that induction of key labor-mediating genes such as IL1 and IL6 was dependent on nuclear factor κB (NF-κB) signaling and reversed by the anti-tumor necrosis factor (TNF) antibody Adalimumab. Inhibition of collagen biosynthesis by IUI was partially restored by Adalimumab. Interestingly, single-cell transcriptomics, flow cytometry, and immunohistology demonstrated that a subset of amnion mesenchymal cells (AMCs) increase CD14 and other myeloid cell markers during IUI both in the human and Rhesus macaque. Our data suggest that CD14+ AMCs represent activated AMCs at the maternal-fetal interface.

Dietary threonine improves muscle nutritional value and muscle hardness associated with collagen synthesis in grass carp (Ctenopharyngodon idella).

To further explain the improvement effect of threonine (Thr) on the fillet quality of fish, a 9-week feeding experiment was conducted. After feeding graded levels of Thr (2.38, 5.38, 8.38, 11.38, 14.38 and 17.38g/kg), the compositions of fillet hydrolyzed amino acid and fatty acid, and the muscle hardness associated with collagen biosynthesis were mainly analyzed in grass carp (Ctenopharyngodon idella). The results showed that Thr increased the pH value, changed the amino acids and fatty acid composition of fillets, especially essential amino acid (EAA), C22:6n3 (DHA) and C20:5n3 (EPA). Furthermore, this study revealed for the first time that the improvement of muscle hardness by Thr was associated with collagen biosynthesis, and the TGF-β1/Smads, LARP6a and Hsp47 regulate transcriptional processes, translation initiation and post-translational modifications in collagen biosynthesis, respectively. This study offered a basis for exploring the contribution of Thr in improving muscle quality in sub-adult grass carp.

Selective reduction of visceral adipose tissue with injectable ice slurry

Reduction in visceral adipose tissue (VAT) mass reduces body weight and metabolic disease risk in obese patients. However surgical removal of VAT is highly invasive and thus not clinically feasible. We developed an injectable ice slurry for selective reduction of adipose tissue through cryolipolysis. The aim of this study was to investigate safety, feasibility and mechanism of ice slurry-induced cryolipolysis of VAT. Perigonadal VAT in diet-induced obese mice and rats was subjected to slurry or sham treatment. Body weight and blood chemistry were monitored for 56 days post-treatment. Histological analysis and molecular studies were performed to elucidate mechanisms of fat reduction. Treatment of VAT was well tolerated in all animals. Slurry induced adipocyte cell death via selective cryolipolysis; significant weight loss was noted at day 21 post-treatment. RNA sequencing from treated VAT samples showed increased expression of genes involved in inflammation, immune response, collagen biosynthesis and wound healing, and decreased expression of adipokines. This study demonstrates that slurry treatment is safe and effective in inducing cryolipolysis of VAT and subsequent weight loss in mice. Ice slurry is promising as a minimally-invasive treatment to reduce visceral adipose tissue.

Whole Exome Sequencing Reveals Two Novel Homozygous Variants in the TRAPPC9 and PLOD3 Genes Leading to Intellectual Disability and Bone Fragility with Contractures

Salt and Pepper’ syndrome is an autosomal recessive condition characterized by severe intellectual disability (ID), epilepsy, scoliosis, choreoathetosis, dysmorphic facial features, and altered dermal pigmentation. IDs are heterogeneous group of disorders prevalent in highly consanguineous populations and genetically variable condition of cognitive impairment linked with behavioral, syndromic, or dysmorphic features. Trafficking protein particle complex subunit 9 ( TRAPPC9) (MIM 611966) is an important gene, and mutations in this gene have been reported to be involved in ID conditions. Lysyl hydroxylase 3 (encoded by ( PLOD3)) is a multifunctional enzyme responsible for catalyzing hydroxylation of lysyl residues and O-glycosylation of hydroxylysyl residues, an important step during posttranslational modifications for collagen biosynthesis. In this study, whole exome sequencing was done for a family member having ID, microcephaly, included joint contractures, low bone mineral density, and dysmorphic feature. We identified a novel missense variant (NM_001160372.3) c.3211G&gt;A, p.G1071S in the exon 22 of TRAPPC9 causing ID and other missense variant c.346G&gt;A, p.V116M (NM_001084.4) in the exon 4 of the PLOD3 gene causing bone fragility with contractures in the affected member of the family. The obtained results were further validated by using Sanger sequencing analysis. The identified variant has not been reported in either gnomAD or Exac databases. Both parents were heterozygous (carriers) to these identified mutations. Our results for the first time suggest that identified novel TRAPPC9 and PLOD3 gene mutations are the main cause of the disease leading to the ID-associated conditions along with cognitive deficits along with microcephaly. This is the first study to report patients with TRAPPC9- and PLOD3-related disorder from Saudi Arabia. This study will add to the literature of the disease and will enable the creation of a database that will provide a strong base to understanding the critical genomic regions to control ID and related disorders in Saudi patients.

Role of some structural features in EPS from microalgae stimulating collagen production by human dermal fibroblasts

ABSTRACTExopolysaccharides (EPS) from the microalgae Porphyridium cruentum, Chrysotila dentata, Pavlova sp., Diacronema sp., Glossomastix sp., Phaeodactylum tricornutum, and Synechococcus sp. were isolated and depolymerized. First, EPS were submitted to a high pressure pre-treatment step, followed by a solid acid-catalyzed hydrolysis step carried out in a batch or recycle fixed-bed reactor, using a strong acidic cation-exchange resin. Twenty-eight different EPS forms were thus obtained. After characterization of their main structural features (weight- and number-averaged molecular weight, polydispersity index, sulfate and uronic acid contents), we investigated the structure–function relationship of their pro-collagen activity. We found that native microalgae EPS were able to inhibit until 27% of human matrix metalloproteinase-1 (MMP-1) activity while the depolymerized forms were able to enhance collagen production by two different human fibroblast lines, used as cell models due to their major role in dermal collagen biosynthesis. The most active EPS forms, obtained by depolymerization in the recycle fixed-bed reactor of D. ennorea and Glossomastix sp. EPS, led to 390% increase in collagen production. Finally, principal component (PCA) and Pearson analyses indicated that MMP-1 inhibition was strongly correlated to the sulfate group content of EPS whereas collagen production by fibroblasts was mostly related to their proportion of low molecular weight polysaccharides (<10 kDa). Uronic acid content of EPS was also shown essential but only if the size of EPS was reduced in the first place. Altogether, these results gave new insights of the dermo-cosmetic potential of microalgae EPS as well as the key parameters of their activity.

New Medical Herbalism Formulations as a Targeted Therapeutic Strategies Used in Southern Tunisia to Promote Neo-Epithelium, Angiogenesis, and Collagen Biosynthesis and to Impede Scar Formation Post-Third-Degree Burned Skin.

The aim of the study is to assess the suitability of the herbal formulation for topical application as a skin burn dressing on the in vivo wound-closure of third-degree wound injuries. Rat wound models were used to prove the in vivo skin burn-healing process. Body weight gain, food and water intake, and behavior were investigated daily during treatment period. Cutaneous biopsies of the burned wound surfaces were monitored at days 4, 13, and 28. Formulation markedly (P < .05) increased wound repair rate and collagen production compared to untreated burnt skin. Macroscopic and histological analysis of the wound of formula (F)-treated group showed significant skin contraction rate and rapid wound healing without scar through regeneration of epidermis that were approved in formula mixed with honey (F-hY)- and Drs-treated wound compared with thymol, and the untreated wound tissues that were not covered by denuded epithelial. Furthermore, the wound healing efficacy of F-hY, F, and Drs cream was proved by decreased the amount of malondialdehyde compared to untreated rats. In conclusion, F and F-hY was found to promote cutaneous wound repair. In all case, the formula alone or mixed with honeybees was even better than thymol in the repair of cutaneous wound.