Structure-activity relationship of synthesized glucans from Ganoderma lucidum with in vitro hypoglycemic activity.

The synthetic polysaccharides, which have precise structure, can be used to design new drugs by comparing structure-activity relationships (SAR). Improved protein stability may be due to the interaction between the polysaccharides and protein, which includes covalent and noncovalent interactions. It is critical to investigate the SAR of polysaccharides with a precise structure from the perspective of protein stability.

Development of novel osteoarthritis therapy by targeting AMPK-β-catenin-Runx2 signaling.

Osteoarthritis (OA) is a debilitating chronic joint disease affecting large populations of patients, especially the elderly. The pathological mechanisms of OA are currently unknown. Multiple risk factors are involved in OA development.

Inhibition of CSPG-PTPσ Activates Autophagy Flux and Lysosome Fusion, Aids Axon and Synaptic Reorganization in Spinal Cord Injury.

Chondroitin sulfate proteoglycans (CSPGs) and proteoglycan receptor protein tyrosine phosphatase σ (PTPσ) play a critical role in the pathology of spinal cord injury (SCI). CSPGs can be induced by autophagy inhibition in astrocyte. However, CSPG's impact on autophagy and its role in SCI is still unknown.

Total Synthesis of Nona-decasaccharide Motif from Polysaccharide Enabled by Modular and One-Pot Stereoselective Glycosylation Strategy.

Polysaccharides from a medicinal fungus represent important and adjunctive therapeutic agents for treating various diseases, including leucopenia and hematopoietic injury. However, the synthetic accessibility to long, branched, and complicated carbohydrates chains from polysaccharides remains a challenging task in chemical synthesis. Here, we report the modular chemical synthesis of nona-decasaccharide motif from polysaccharide GSPB70-S with diverse biological activities for the first time through one-pot stereoselective glycosylation strategy on the basis of glycosyl -(1-phenyvinyl)benzoates, which not only sped up carbohydrates synthesis but also reduced chemical waste and avoided aglycones transfer issues inherent to one-pot glycosylation on the basis of thioglycosides.

Pip5k1γ promotes anabolism of nucleus pulposus cells and intervertebral disc homeostasis by activating CaMKII-Ampk pathway in aged mice.

Degenerative disc disease (DDD) represents a significant global health challenge, yet its underlying molecular mechanisms remain elusive. This study aimed to investigate the role of type 1 phosphatidylinositol 4-phosphate 5-kinase (Pip5k1) in intervertebral disc (IVD) homeostasis and disease. All three Pip5k1 isoforms, namely Pip5k1α, Pip5k1β, and Pip5k1γ, were detectable in mouse and human IVD tissues, with Pip5k1γ displaying a highest expression in nucleus pulposus (NP) cells.

Bone transport induces the release of factors with multi-tissue regenerative potential for diabetic wound healing in rats and patients.

Tibial cortex transverse distraction is a surgical method for treating severe diabetic foot ulcers (DFUs), but the underlying mechanism is unclear. We show that antioxidant proteins and small extracellular vesicles (sEVs) with multiple-tissue regenerative potential are released during bone transport (BT) in humans and rats. These vesicles accumulate in diabetic wounds and are enriched with microRNAs (miRNAs) (e.

Noncoding RNAs in skeletal development and disorders.

Protein-encoding genes only constitute less than 2% of total human genomic sequences, and 98% of genetic information was previously referred to as "junk DNA". Meanwhile, non-coding RNAs (ncRNAs) consist of approximately 60% of the transcriptional output of human cells. Thousands of ncRNAs have been identified in recent decades, and their essential roles in the regulation of gene expression in diverse cellular pathways associated with fundamental cell processes, including proliferation, differentiation, apoptosis, and metabolism, have been extensively investigated.

An integrated multi-omics analysis reveals osteokines involved in global regulation.

Bone secretory proteins, termed osteokines, regulate bone metabolism and whole-body homeostasis. However, fundamental questions as to what the bona fide osteokines and their cellular sources are and how they are regulated remain unclear. In this study, we analyzed bone and extraskeletal tissues, osteoblast (OB) conditioned media, bone marrow supernatant (BMS), and serum, for basal osteokines and those responsive to aging and mechanical loading/unloading.

Pip5k1c expression in osteocytes regulates bone remodeling in mice.

Research Background: The role of osteocytes in maintaining bone mass has been progressively emphasized. Pip5k1c is the most critical isoform among PIP5KIs, which can regulate cytoskeleton, biomembrane, and Ca release of cells and participate in many processes, such as cell adhesion, differentiation, and apoptosis. However, its expression and function in osteocytes are still unclear.

Atomic-Level Dissection of DC-SIGN Recognition of LPS Epitopes.

The evaluation of mpk (BVMPK) lipopolysaccharide (LPS) recognition by DC-SIGN, a key lectin in mediating immune homeostasis, has been here performed. A fine chemical dissection of BVMPK LPS components, attained by synthetic chemistry combined to spectroscopic, biophysical, and computational techniques, allowed to finely map the LPS epitopes recognized by DC-SIGN. Our findings reveal BVMPK's role in immune modulation via DC-SIGN, targeting both the LPS O-antigen and the core oligosaccharide.

Epigenetic regulations of cellular senescence in osteoporosis.

Osteoporosis (OP) is a prevalent age-related disease that is characterized by a decrease in bone mineral density (BMD) and systemic bone microarchitectural disorders. With age, senescent cells accumulate and exhibit the senescence-associated secretory phenotype (SASP) in bone tissue, leading to the imbalance of bone homeostasis, osteopenia, changes in trabecular bone structure, and increased bone fragility. Cellular senescence in the bone microenvironment involves osteoblasts, osteoclasts, and bone marrow mesenchymal stem cells (BMSCs), whose effects on bone homeostasis are regulated by epigenetics.

Highly Stereoselective Synthesis of Branched Fructooligosaccharides ABW90-1 and ABW50-1 from with Potent Antiosteoporosis Activities.

The branched fructooligosaccharides ABW90-1 and ABW50-1 from with potent antiosteoporosis activities have been synthesized for the first time. The synthetic approach highlights the following features: (1) 6--picoloyl-directed β-d-fructofuranosylation via a hydrogen-bond-mediated aglycone delivery strategy for the highly stereoselective constructions of β-(2 → 6)-d-fructofuranosidic linkages and β-(2 → 1)-d-fructofuranosidic linkages in the internal positions under the reaction conditions (DBDMH, -20 °C, CHCl) and (2) the reaction conditions (DBDMH, -78 °C to -35 °C, toluene) for highly stereoselective formations of β-(2 → 1)-d-fructofuranosidic linkages in the terminal positions.

One-Pot Assembly of Mannose-Capped Lipoarabinomannan Motifs up to 101-Mer from the Cell Wall.

Lipoarabinomannan (LAM) from the cell envelope represents important targets for the development of new therapeutic agents against tuberculosis, which is a deadly disease that has plagued mankind for a long time. However, the accessibility of long, branched, and complex lipoarabinomannan over 100-mer remains a long-standing challenge. Herein, we report the modular synthesis of mannose-capped lipoarabinomannan 101-mer from the cell wall using a one-pot assembly strategy on the basis of glycosyl -(1-phenylvinyl)benzoates (PVB), which not only accelerates the modular synthesis but also precludes the potential problems associated with one-pot glycosylation with thioglycosides.

Kindlin-2 maintains liver homeostasis by regulating GSTP1-OPN-mediated oxidative stress and inflammation in mice.

Hepatocyte plays a principal role in preserving integrity of the liver homeostasis. Our recent study demonstrated that Kindlin-2, a focal adhesion protein that activates integrins and regulates cell-extracellular matrix interactions, plays an important role in regulation of liver homeostasis by inhibiting inflammation pathway; however, the molecular mechanism of how Kindlin-2 KO activates inflammation is unknown. Here, we show that Kindlin-2 loss largely downregulates the antioxidant glutathione-S-transferase P1 in hepatocytes by promoting its ubiquitination and degradation via a mechanism involving protein-protein interaction.

Primary Astrocytes Purification and Immortalization.

Astrocytes, the most abundant cells in the central nervous system (CNS), are essential for neuronal development, network formation, and overall CNS homeostasis. Primary astrocyte culture has been successfully used as a tool to study astrocyte biology in vitro. In the present protocol, a modified immunopanning method was utilized to obtain and purify primary astrocytes from mouse cortex and spinal cord in a relatively quick and inexpensive way.

Sensory nerves directly promote osteoclastogenesis by secreting peptidyl-prolyl cis-trans isomerase D (Cyp40).

Given afferent functions, sensory nerves have recently been found to exert efferent effects and directly alter organ physiology. Additionally, several studies have highlighted the indirect but crucial role of sensory nerves in the regulation of the physiological function of osteoclasts. Nonetheless, evidence regarding the direct sensory nerve efferent influence on osteoclasts is lacking.

Pathological progress and remission strategies of osteoarthritic lesions caused by long-term joint immobilization.

Objective: While joint immobilization is a useful repair method for intra-articular ligament injury and periarticular fracture, prolonged joint immobilization can cause multiple complications. A better understanding how joint immobilization and remobilization impact joint function and homeostasis will help clinicians develop novel strategies to reduce complications.

Design: We first determined the effects of long-term immobilization on joint pain and osteophyte formation in patients after an extraarticular fracture or ligament injury.

The bone-liver interaction modulates immune and hematopoietic function through Pinch-Cxcl12-Mbl2 pathway.

Mesenchymal stromal cells (MSCs) are used to treat infectious and immune diseases and disorders; however, its mechanism(s) remain incompletely defined. Here we find that bone marrow stromal cells (BMSCs) lacking Pinch1/2 proteins display dramatically reduced ability to suppress lipopolysaccharide (LPS)-induced acute lung injury and dextran sulfate sodium (DSS)-induced inflammatory bowel disease in mice. Prx1-Cre; Pinch1; Pinch2 transgenic mice have severe defects in both immune and hematopoietic functions, resulting in premature death, which can be restored by intravenous injection of wild-type BMSCs.