Adenosine diphosphate released from stressed cells triggers mitochondrial transfer to achieve tissue homeostasis.

Cell-to-cell mitochondrial transfer has recently been shown to play a role in maintaining physiological functions of cell. We previously illustrated that mitochondrial transfer within osteocyte dendritic network regulates bone tissue homeostasis. However, the mechanism of triggering this process has not been explored. Here, we showed that stressed osteocytes in mice release adenosine diphosphate (ADP), resulting in triggering mitochondrial transfer from healthy osteocytes to restore the oxygen consumption rate (OCR) and to alleviate reactive oxygen species accumulation. Furthermore, we identified that P2Y2 and P2Y6 transduced the ADP signal to regulate osteocyte mitochondrial transfer. We showed that mitochondrial metabolism is impaired in aged osteocytes, and there were more extracellular nucleotides release into the matrix in aged cortical bone due to compromised membrane integrity. Conditioned medium from aged osteocytes triggered mitochondrial transfer between osteocytes to enhance the energy metabolism. Together, using osteocyte as an example, this study showed new insights into how extracellular ADP triggers healthy cells to rescue energy metabolism crisis in stressed cells via mitochondrial transfer in tissue homeostasis.

The Antibacterial Activity Mode of Action of Plantaricin YKX against Staphylococcus aureus.

We aimed to evaluate the inhibitory effect and mechanism of plantaricin YKX on S. aureus. The mode of action of plantaricin YKX against the cells of S. aureus indicated that plantaricin YKX was able to cause the leakage of cellular content and damage the structure of the cell membranes. Additionally, plantaricin YKX was also able to inhibit the formation of S. aureus biofilms. As the concentration of plantaricin YKX reached 3/4 MIC, the percentage of biofilm formation inhibition was over 50%. Fluorescent dye labeling combined with fluorescence microscopy confirmed the results. Finally, the effect of plantaricin YKX on the AI-2/LuxS QS system was investigated. Molecular docking predicted that the binding energy of AI-2 and plantaricin YKX was -4.7 kcal/mol and the binding energy of bacteriocin and luxS protein was -183.701 kcal/mol. The expression of the luxS gene increased significantly after being cocultured with plantaricin YKX, suggesting that plantaricin YKX can affect the QS system of S. aureus.

Osthole stimulates bone formation, drives vascularization and retards adipogenesis to alleviate alcohol-induced osteonecrosis of the femoral head.

Characteristic pathological changes in osteonecrosis of the femoral head (ONFH) include reduced osteogenic differentiation of bone mesenchymal stem cells (BMSCs), impaired osseous circulation and increased intramedullary adipocytes deposition. Osthole is a bioactive derivative from coumarin with a wide range of pharmacotherapeutic effects. The aim of this study was to unveil the potential protective role of osthole in alcohol-induced ONFH. In vitro, ethanol (50 mmol/L) remarkably decreased the proliferation and osteogenic differentiation of BMSCs and impaired the proliferation and tube formation capacity of human umbilical vein endothelial cell (HUVECs), whereas it substantially promoted the adipogenic differentiation of BMSCs. However, osthole could reverse the effects of ethanol on osteogenesis via modulating Wnt/ß-catenin pathway, stimulate vasculogenesis and counteract adipogenesis. In vivo, the protective role of osthole was confirmed in the well-constructed rat model of ethanol-induced ONFH, demonstrated by a cascade of radiographical and pathological investigations including micro-CT scanning, haematoxylin-eosin staining, TdT-mediated dUTP nick end labelling, immunohistochemical staining and fluorochrome labelling. Taken together, for the first time, osthole was demonstrated to rescue the ethanol-induced ONFH via promoting bone formation, driving vascularization and retarding adipogenesis.

Horizontal fissuring at the osteochondral interface: a novel and unique pathological feature in patients with obesity-related osteoarthritis.

OBJECTIVES: Obesity is a well-recognised risk factor for osteoarthritis (OA). Our aim is to characterise body mass index (BMI)-associated pathological changes in the osteochondral unit and determine if obesity is the major causal antecedent of early joint replacement in patients with OA. METHODS: We analysed the correlation between BMI and the age at which patients undergo total knee replacement (TKR) in 41 023 patients from the Australian Orthopaedic Association National Joint Replacement Registry. We then investigated the effect of BMI on pathological changes of the tibia plateau of knee joint in a representative subset of the registry. RESULTS: 57.58% of patients in Australia who had TKR were obese. Patients with overweight, obese class I & II or obese class III received a TKR 1.89, 4.48 and 8.08 years earlier than patients with normal weight, respectively. Microscopic examination revealed that horizontal fissuring at the osteochondral interface was the major pathological feature of obesity-related OA. The frequency of horizontal fissure was strongly associated with increased BMI in the predominant compartment. An increase in one unit of BMI (1 kg/m2) increased the odds of horizontal fissures by 14.7%. 84.4% of the horizontal fissures were attributable to obesity. Reduced cartilage degradation and alteration of subchondral bone microstructure were also associated with increased BMI. CONCLUSIONS: The key pathological feature in OA patients with obesity is horizontal fissuring at the osteochondral unit interface. Obesity is strongly associated with a younger age of first TKR, which may be a result of horizontal fissures.

Simultaneous dislocation of the radial head and distal radio-ulnar joint without fracture in an adult patient: a case report and review of literature.

BACKGROUND: Simultaneous dislocation of the radial head and distal radio-ulnar joint without fracture (Criss-Cross Injury) in an adult patient is rarely reported in previous studies. The pathological changes and injury patterns have not been clearly demonstrated. CASE PRESENTATION: A 26-year-old woman presented with acute pain of the right wrist and elbow after a fall from cycling. Physical examination revealed an unstable elbow and wrist joint. Plain radiographs showed volar dislocation of the radial head and dorsal dislocation of the distal radius without associated fracture, forming a criss-cross appearance of the ulna and radius on the lateral radiograph. MRI images confirmed partial rupture of the proximal interosseous membrane from its dorsal attachment on the radius, as well as partial rupture of the medial collateral ligament. Conservative treatment failed because the radiocapitellar joint and distal radio-ulnar joint could not be simultaneously reduced. Surgical exploration revealed a highly unstable radial head, but the annular ligament was found to be intact. Manual force was applied to reduce the radial head and a percutaneous K-wire was used to stabilize the proximal radioulnar joint with the forearm in full supination. After surgery, the elbow was immobilized in 90° flexion by a long arm cast for 4 weeks. The K-wire was removed at 6 weeks postoperatively. At 18 months postoperatively, the patient had regained a full range of flexion and extension, with normal supination and a slight limitation in pronation. CONCLUSIONS: The proximal IOM, especially the dorsal band, was injured in Criss-Cross injuries, while the central part of the IOM remained intact. This injury pattern distinguished itself from Essex-Lopresti injury, which mainly involves rupture of the central band of the IOM.

Bone marrow lesion on magnetic resonance imaging indicates the last chance for hip osteonecrosis treated with vascularized fibular grafting before collapse.

PURPOSE: Timing of surgery is the most critical prognostic factor for hip osteonecrosis treated with free vascularized fibular grafting (FVFG). Bone marrow lesion (BML) on MRI usually occurs immediately before femoral head collapse. We conducted a retrospective cohort study to evaluate whether the noncollapsed hips with BML can benefit from FVFG. METHODS: Consecutive patients undergoing modified FVFG were identified from our clinical repository between January 2014 and December 2014. Based on whether BML was pre-operatively detected, the four year radiographic and clinical outcomes were compared. RESULTS: In the BML cohort, 22 of 53 hips (42%) showed radiographic signs of osteonecrosis progression, which was significantly higher than that in the control cohort (8 of 49, 16%; P = 0.005). The BML hips showed a significantly lower pre-operative Harris Hip Score (HHS) than those without BML (77.8 vs. 85.5, P = 0.046), whereas no such difference was observed in the final HHS or its post-operative improvement (HHS 90 vs. 94, P = 0.397; HHS improvement 12 vs. 8, P = 0.067). In the subgroup of patients with a pre-operative HHS lower than 80, BML hips were associated with a slightly lower final HHS than hips without BML. Four of 5 (80%) failed hips with BML had a poor pre-operative hip function. CONCLUSION: BML indicates the last chance for a reproducible improvement in the treatment of hip osteonecrosis with FVFG before collapse. However, the concomitant lower pre-operative HHS (< 80) is a poor prognostic factor for BML-positive hips.

Distally based perforator propeller sural flap for foot and ankle reconstruction: a modified flap dissection technique.

BACKGROUND: Distally based perforator propeller sural flaps that pedicled on an isolated perforator from the peroneal artery or posterior tibial artery are a versatile local reconstructive option for defects of the foot and ankle region. However, flap venous congestion is yet a difficult problem after operation. We hypothesize that containing some adipofascial tissues around the axial perforator can preserve some tiny venous return routes, improve venous drainage, and ultimately enhance flap safety in distally based sural flaps. METHODS: A prospective case series of 12 patients undergoing distally based perforator sural flaps for foot and ankle coverage were included in this study from January 2008 to December 2010. There were 7 posterior tibial artery perforator flaps from the posteromedial sural region and 5 peroneal artery perforator flaps from the posterolateral sural region. After identifying the proper viable perforator during operation as the pivot point, the whole flap was designed in an eccentric propeller shape. The proximal larger blade was a fasciocutaneous flap, whereas the distal smaller blade was a subdermal vascular plexus flap, preserving at least a quarter area of adipofascial tissue intact around the perforator. Postoperatively, flap swelling was classified into a 5-grade assessment scale. Flap survival, complications, and patient functional recovery were evaluated. RESULTS: The proximal fasciocutaneous flap measured 4 × 8 to 6 × 18 cm (mean, 57.8 cm), and the distal subdermal cutaneous flap measured 2 × 2 to 4 × 4 cm (mean, 9.2 cm). The flaps were rotated 160 to 180 degrees. Postoperatively, flap swelling was noted under grade 2 in 9 cases, grade 3 in 2, and grade 4 in 1 with some distal superficial skin necrosis, which occurred in the largest flap in our series. All flaps survived uneventfully. After a mean of 13 months of follow-up, the wounds were cured successfully. All patients recovered walking and shoe wearing function. CONCLUSION: Keeping a quadrant adipofascial tissue around the distal pivot perforator to form a perforator-adipofascial-pedicle can preserve more venous return routes and relieve flap swelling. This technique should be recommended in distally perforator-pedicled propeller flaps because it enhances flap safety yet does not increase the difficulty of 180-degree rotation.

Mitochondria from osteolineage cells regulate myeloid cell-mediated bone resorption.

Interactions between osteolineage cells and myeloid cells play important roles in maintaining skeletal homeostasis. Herein, we find that osteolineage cells transfer mitochondria to myeloid cells. Impairment of the transfer of mitochondria by deleting MIRO1 in osteolineage cells leads to increased myeloid cell commitment toward osteoclastic lineage cells and promotes bone resorption. In detail, impaired mitochondrial transfer from osteolineage cells alters glutathione metabolism and protects osteoclastic lineage cells from ferroptosis, thus promoting osteoclast activities. Furthermore, mitochondrial transfer from osteolineage cells to myeloid cells is involved in the regulation of glucocorticoid-induced osteoporosis, and glutathione depletion alleviates the progression of glucocorticoid-induced osteoporosis. These findings reveal an unappreciated mechanism underlying the interaction between osteolineage cells and myeloid cells to regulate skeletal metabolic homeostasis and provide insights into glucocorticoid-induced osteoporosis progression.

Regulation of blood-brain barrier integrity by Dmp1-expressing astrocytes through mitochondrial transfer.

The blood-brain barrier (BBB) acts as the crucial physical filtration structure in the central nervous system. Here, we investigate the role of a specific subset of astrocytes in the regulation of BBB integrity. We showed that Dmp1-expressing astrocytes transfer mitochondria to endothelial cells via their endfeet for maintaining BBB integrity. Deletion of the Mitofusin 2 (Mfn2) gene in Dmp1-expressing astrocytes inhibited the mitochondrial transfer and caused BBB leakage. In addition, the decrease of MFN2 in astrocytes contributes to the age-associated reduction of mitochondrial transfer efficiency and thus compromises the integrity of BBB. Together, we describe a mechanism in which astrocytes regulate BBB integrity through mitochondrial transfer. Our findings provide innnovative insights into the cellular framework that underpins the progressive breakdown of BBB associated with aging and disease.

Costal cartilage grafting in the treatment of concurrent osteochondral lesion of the talus in a trimalleolar fracture.

A 49-year-old female sustained a trimalleolar fracture concurrent with 10 years history of symptomatic osteochondral lesions of the talus. We performed a costal cartilage grafting for osteochondral lesions of the talus through the inherent medial malleolar fracture gap, followed by internal fixation of the fracture. During the follow-up, the fracture healed within the expected time, accompanied by favorable functional outcomes and pre-injury pain relief. At 3 years postoperatively, the graft merged with the bone bed of the talus, and progressive endochondral ossification was observed at the graft-bone interface. The case provides us a chance to verify whether the costal cartilage grafting is reliable for the treatment of osteochondral lesions of the talus.

Costal Cartilage Graft Repair Osteochondral Defect in a Mouse Model.

OBJECTIVE: Osteochondral defects develop into osteoarthritis without intervention. Costal cartilage can be utilized as an alternative source for repairing osteochondral defect. Our previous clinical study has shown the successful osteochondral repair by costal cartilage graft with integration into host bone bed. In this study, we investigate how cartilaginous graft adapt to osteochondral environment and the mechanism of bone-cartilage interface formation. DESIGN: Costal cartilage grafting was performed in C57BL/6J mice and full-thickness osteochondral defect was made as control. 3D optical profiles and micro-CT were applied to evaluate the reconstruction of articular cartilage surface and subchondral bone as well as gait analysis to evaluate articular function. Histological staining was performed at 2, 4, and 8 weeks after surgery. Moreover, costal cartilage from transgenic mice with fluorescent markers were transplanted into wild-type mice to observe the in vivo changes of costal chondrocytes. RESULTS: At 8 weeks after surgery, 3D optical profiles and micro-CT showed that in the graft group, the articular surface and subchondral bone were well preserved. Gait analysis and International Cartilage Repair Society (ICRS) score evaluation showed a good recovery of joint function and histological repair in the graft group. Safranin O staining showed the gradual integration of graft and host tissue. Costal cartilage from transgenic mice with fluorescent markers showed that donor-derived costal chondrocytes turned into osteocytes in the subchondral area of host femur. CONCLUSION: Costal cartilage grafting shows both functional and histological repair of osteochondral defect in mice. Graft-derived costal chondrocytes differentiate into osteocytes and contribute to endochondral ossification.

Application of Graphene and its Derivatives in Detecting Hazardous Substances in Food: A Comprehensive Review.

Graphene and its derivatives have been a burning issue in the last 10 years. Although many reviews described its application in electrochemical detection, few were focused on food detection. Herein, we reviewed the recent progress in applying graphene and composite materials in food detection during the past 10 years. We pay attention to food coloring materials, pesticides, antibiotics, heavy metal ion residues, and other common hazards. The advantages of graphene composites in electrochemical detection are described in detail. The differences between electrochemical detection involving graphene and traditional inherent food detection are analyzed and compared in depth. The results proved that electrochemical food detection based on graphene composites is more beneficial. The current defects and deficiencies in graphene composite modified electrode development are discussed, and the application prospects and direction of graphene in future food detection are forecasted.

Effect of Chitosan/Thyme Oil Coating and UV-C on the Softening and Ripening of Postharvest Blueberry Fruits.

This study investigated the possible mechanism of softening and senescence of blueberry after harvest using chitosan/thyme oil coating combined with UV-C (short wave ultraviolet irradiation) treatment. On the 56th day of storage, the CBP, cellulose, and hemicellulose contents in the chitosan/thyme oil coating +UV-C-treated group were 1.41, 1.65, and 1.20 times higher than those in the control group. Compared with the control group, the activities of polygalacturonase (PG), pectin methylesterase (PME), ß-glucosidase (ß-Gal), and cellulose (Cx) were significantly reduced (p < 0.05) after chitosan/thyme oil coating +UV-C, and their maximum values decreased by 5.41 µg/h g, 5.40 U/g, 12.41 U/g, and 3.85 µg/h g, respectively. Moreover, chitosan/thyme oil coating combined with UV-C treatment inhibited the gene expression of PG, PME, Cx, and ß-Gal and then regulated the decrease in PG, PME, Cx, and ß-Gal activities, inhibited the degradation of cell wall polysaccharides, and delayed the softening and senescence of postharvest blueberries. The results showed that chitosan/thyme oil coating, UV-C, and chitosan/thyme oil coating + UV-C could significantly inhibit postharvest softening of blueberry; chitosan/thyme oil coating +UV-C had the best effect.

Potential Use of Emerging Technologies for Preservation of Rice Wine and Their Effects on Quality: Updated Review.

Rice wine, a critical fermented alcoholic beverage, has a considerable role in different cultures. It contains compounds that may have functional and nutritional health benefits. Bacteria, yeasts, and fungi commonly found in rice wines during fermentation can induce microbial spoilage and deterioration of the quality during its distribution and aging processes. It is possible to control the microbial population of rice wines using different preservation techniques that can ultimately improve their commercial shelf life. This paper reviews the potential techniques that can be used to preserve the microbial safety of rice wines while maintaining their quality attributes and further highlights the advantages and disadvantages of each technique.

Osteocytes regulate senescence of bone and bone marrow.

The skeletal system contains a series of sophisticated cellular lineages arising from the mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) that determine the homeostasis of bone and bone marrow. Here, we reasoned that osteocyte may exert a function in regulation of these lineage cell specifications and tissue homeostasis. Using a mouse model of conditional deletion of osteocytes by the expression of diphtheria toxin subunit α in dentin matrix protein 1 (DMP1)-positive osteocytes, we demonstrated that partial ablation of DMP1-positive osteocytes caused severe sarcopenia, osteoporosis, and degenerative kyphosis, leading to shorter lifespan in these animals. Osteocytes reduction altered mesenchymal lineage commitment, resulting in impairment of osteogenesis and induction of osteoclastogensis. Single-cell RNA sequencing further revealed that hematopoietic lineage was mobilized toward myeloid lineage differentiation with expanded myeloid progenitors, neutrophils, and monocytes, while the lymphopoiesis was impaired with reduced B cells in the osteocyte ablation mice. The acquisition of a senescence-associated secretory phenotype (SASP) in both osteogenic and myeloid lineage cells was the underlying cause. Together, we showed that osteocytes play critical roles in regulation of lineage cell specifications in bone and bone marrow through mediation of senescence.

A hallmark of aging is the weakening of our muscles and bones, which become more fragile as we get older. These gradual changes can result in a humpback and muscle shrinking among other conditions. At the same time little is known about what role osteocytes ­ the most abundant type of bone cell ­ play in the process of bone and muscle aging. One way to investigate the role of osteocytes in aging is to remove them and observe what happens to nearby cells as they age. To achieve this Ding, Gao, Gao et al. genetically altered mice so that they would carry and activate a gene called DTA in their osteocytes. DTA is a gene derived from the bacterium that causes diphtheria, and when it is activated, it produces a toxin that accumulates in cells, eventually killing them. In the mice line developed by Ding, Gao, Gao et al. DTA slowly killed osteocytes, leading to adult mice lacking most of their osteocyte population that have a normal embryonic development. This is important because the fact that the mice develop normally before birth allowed the team to rule out embryonic defects when looking at their results. Ding, Gao, Gao et al. found that, without enough osteocytes, the nearby bone and bone marrow cells aged faster than expected. Indeed, the skeleton and muscles of adult mice was severely affected by the loss of osteocytes, leading to fragile bones with lower mass and muscle shrinking. These mice looked old in their young age and died earlier. At the cellular level, the removal of osteocytes impaired the formation of osteoblasts, the cells that are responsible for making bones. It also led to an increase in the numbers of osteoclasts ­ the cells that destroy bone tissue to repair it and maintain it ­ and fat tissue cells. Furthermore, cells in the bone marrow, which go on to make white blood cells, were also affected. The mechanisms through which osteocytes affect the growth of these other cells is yet to be fully understood. However, Ding, Gao, Gao et al. did observe that these cells acquired traits characteristic of aging cells, implying that osteocytes have a role in regulating cellular aging or senescence. Among these senescence traits is the increased production and secretion of molecules that interact with the immune system, a feature known as the 'senescence-associated secretory phenotype'. Overall, the results of Ding, Gao, Gao et al. suggest that reducing the number of osteocytes in mice leads to faster bone aging and affects the balance of the different cell types required for healthy bone and bone marrow growth. Future research could focus on finding drugs that allow osteocytes to keep performing their role during aging, and thus help maintain bone health. The findings of Ding, Gao, Gao et al. also suggest that osteocytes may be playing a previously underappreciated role in age-related diseases, which warrants further investigation.

Single-cell transcriptomics identifies premature aging features of TERC-deficient mouse brain and bone marrow.

Aging is a progressive loss of physiological function and increased susceptibility to major pathologies. Degenerative diseases in both brain and bone including Alzheimer disease (AD) and osteoporosis are common in aging groups. TERC is RNA component of telomerase, and its deficiency accelerates aging-related phenotypes including impaired life span, organ failure, bone loss, and brain dysfunction. In this study, we investigated the traits of bone marrow-brain cross-tissue communications in young mice, natural aging mice, and premature aging (TERC deficient, TERC-KO) mice by single-cell transcriptome sequencing. Differentially expressed gene analysis of brain as well as bone marrow between premature aging mouse and young mouse demonstrated aging-related inflammatory response and suppression of neuron development. Further analysis of senescence-associated secretory phenotype (SASP) landscape indicated that TERC-KO perturbation was enriched in oligodendrocyte progenitor cells (OPCs) and hematopoietic stem and progenitor cells (HSPC). Series of inflammatory associated myeloid cells was activated in premature aging mice brain and bone marrow. Cross-tissue comparison of TERC-KO mice brain and bone marrow illustrated obvious ligand-receptor communications between brain glia cells, macrophages, and bone marrow myeloid cells in premature aging-induced inflammation. Enrichment of co-regulation modules between brain and bone marrow identified premature aging response genes such as Dusp1 and Ifitm3. Our study provides a rich resource for understanding premature aging-associated perturbation in brain and bone marrow and supporting myeloid cells and endothelial cells as promising therapy targeting for age-related brain-bone diseases.

Autologous Costal Cartilage Grafting for a Large Osteochondral Lesion of the Femoral Head: A 1-Year Single-Arm Study with 2 Additional Years of Follow-up.

BACKGROUND: There is currently no ideal treatment for osteochondral lesions of the femoral head (OLFH) in young patients. METHODS: We performed a 1-year single-arm study and 2 additional years of follow-up of patients with a large (defined as >3 cm 2 ) OLFH treated with insertion of autologous costal cartilage graft (ACCG) to restore femoral head congruity after lesion debridement. Twenty patients ≤40 years old who had substantial hip pain and/or dysfunction after nonoperative treatment were enrolled at a single center. The primary outcome was the change in Harris hip score (HHS) from baseline to 12 months postoperatively. Secondary outcomes included the EuroQol visual analogue scale (EQ VAS), hip joint space width, subchondral integrity on computed tomography scanning, repair tissue status evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and evaluation of cartilage biochemistry by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping. RESULTS: All 20 enrolled patients (31.02 ± 7.19 years old, 8 female and 12 male) completed the initial study and the 2 years of additional follow-up. The HHS improved from 61.89 ± 6.47 at baseline to 89.23 ± 2.62 at 12 months and 94.79 ± 2.72 at 36 months. The EQ VAS increased by 17.00 ± 8.77 at 12 months and by 21.70 ± 7.99 at 36 months (p < 0.001 for both). Complete integration of the ACCG with the bone was observed by 12 months in all 20 patients. The median MOCART score was 85 (interquartile range [IQR], 75 to 95) at 12 months and 75 (IQR, 65 to 85) at the last follow-up (range, 24 to 38 months). The ACCG demonstrated magnetic resonance properties very similar to hyaline cartilage; the median ratio between the relaxation times of the ACCG and recipient cartilage was 0.95 (IQR, 0.90 to 0.99) at 12 months and 0.97 (IQR, 0.92 to 1.00) at the last follow-up. CONCLUSIONS: ACCG is a feasible method for improving hip function and quality of life for at least 3 years in young patients who were unsatisfied with nonoperative treatment of an OLFH. Promising long-term outcomes may be possible because of the good integration between the recipient femoral head and the implanted ACCG. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Purification and Characterization of Plantaricin YKX and Assessment of Its Inhibitory Activity Against Alicyclobacillus spp.

Consumers prefer natural over synthetic chemical preservatives on a food label. Therefore, it is crucial to ensure the safety and efficacy of such natural preservatives. The emergence of heat-resistant spore-forming Alicyclobacillus spp. has been associated with spoilage problems in the fruit juice industry. Herein, a bacteriocin-producing stain YKX was isolated from the traditional pickles in Hanzhong City, China, and it was identified as Lactobacillus plantarum by morphological, biochemical, physiological, and genotypic features. A stable bacteriocin, plantaricin YKX, was isolated, purified, and tested for its efficacy against Alicyclobacillus acidoterrestris. Plantaricin YKX is a 14-amino acid peptide (Lys-Tyr-Gly-Asn-Gly-Leu-Ser-Arg-Ile-Phe-Ser-Ala-Leu-Lys). Its minimal inhibitory concentrations (MICs) against the tested bacterial and fungal strains were ranged from 16 to 64 µg/mL. It is thermostable and active at pH 3-8. The flow cytometry data and microscopic observations suggested that plantaricin YKX can augment cell membrane permeability, induce potassium ion leakage and pore formation, and disrupt cell membranes. It also affects spore germination and guaiacol production of A. acidoterrestris, probably due to upregulation of the luxS gene linked to quorum sensing.

miR-4286 functions in osteogenesis and angiogenesis via targeting histone deacetylase 3 and alleviates alcohol-induced bone loss in mice.

OBJECTIVES: Alcohol consumption is one of the leading factors contributing to premature osteopenia. MicroRNA (miRNA) coordinates a cascade of anabolic and catabolic processes in bone homeostasis and dynamic vascularization. The aim was to investigate the protective role of miR-4286 in alcohol-induced bone loss and its mechanism. MATERIALS AND METHODS: The effect of miR-4286 and alcohol on bone mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) was explored via multiple in vitro assays, including cell proliferation, QPCR, Western blot, osteogenesis, angiogenesis etc miR-4286 directly regulated HDAC3 was investigated by luciferase reporter assay, and the function of HDAC3 was also explored in vitro. Moreover, alcohol-induced bone loss in mice was established to reveal the preventive effect of miR-4286 by radiographical and histopathological assays. RESULTS: In vitro, ethanol dramatically inhibited the proliferation and osteogenesis of BMSCs, and substantially impaired the proliferation and vasculogenesis of HUVECs. However, a forced overexpression of miR-4286 within BMSCs and HUVECs could largely abolish inhibitory effects by alcohol. Furthermore, alcohol-induced inhibition on osteogenic and vasculogenic functions was mediated by histone deacetylase 3 (HDAC3), and dual-luciferase reporter assay showed that HDAC3 was the direct binding target of miR-4286. In vivo, micro-CT scanning and histology assessment revealed that miR-4286 could prevent alcohol-induced bone loss. CONCLUSIONS: We firstly demonstrated that miR-4286 might function via intimate osteogenesis-angiogenesis pathway to alleviate alcohol-induced osteopenia via targeting HDAC3.

Intercellular mitochondrial transfer as a means of tissue revitalization.

As the crucial powerhouse for cell metabolism and tissue survival, the mitochondrion frequently undergoes morphological or positional changes when responding to various stresses and energy demands. In addition to intracellular changes, mitochondria can also be transferred intercellularly. Besides restoring stressed cells and damaged tissues due to mitochondrial dysfunction, the intercellular mitochondrial transfer also occurs under physiological conditions. In this review, the phenomenon of mitochondrial transfer is described according to its function under both physiological and pathological conditions, including tissue homeostasis, damaged tissue repair, tumor progression, and immunoregulation. Then, the mechanisms that contribute to this process are summarized, such as the trigger factors and transfer routes. Furthermore, various perspectives are explored to better understand the mysteries of cell-cell mitochondrial trafficking. In addition, potential therapeutic strategies for mitochondria-targeted application to rescue tissue damage and degeneration, as well as the inhibition of tumor progression, are discussed.