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Objective: Female urethral diverticulum (UD), an evagination of the urethral mucosa into the surrounding connective tissue, is extremely rare in pregnancy. No clear guidelines on the optimal management of UD have been established, except for a common conservative approach. Here, we discuss how to manage UD with pregnancy. Case report: A 39-year-old gravida 4, para 0, abortion 3 (G4P0A3) woman at 34+0 gestational weeks (GW) visited our outpatient department with a 6-cm septate vaginal mass. Transvaginal ultrasound sonography (TVUS) revealed a 5.5 x 4.9-cm multicystic mass, which was confirmed as UD with pelvic MRI. She was admitted because of preterm labor. A cesarean section was performed at 36+5 GW due to a previous myomectomy, and a healthy male baby was born. UD was still observed in the patient two months after delivery. Periurethral diverticulectomy was performed, and pathological analysis revealed UD with chronic inflammation and edema. Conclusion: Previous reports and our case report show that UD can develop during pregnancy and that pelvic MRI is suitable for its accurate diagnosis. Vaginal delivery is possible in pregnant women with the small size of the UD. UD aspiration can permit vaginal delivery in a few cases; however, pus can occur at the aspirated site after the operation. If UD is still observed after delivery, urethral diverticulectomy is recommended.

The partial nitritation (PN)–anammox (PN/A) process offers a sustainable alternative to nitrogen management in wastewater treatment, addressing the high costs and increasing the low eco-friendliness associated with traditional nitrification/denitrification processes. Stable partial nitritation (PN) is critical for effective PN/A operation, and this study specifically focused on the need to suppress nitrite-oxidizing bacteria (NOB) to facilitate the enrichment of ammonia-oxidizing bacteria (AOB). Utilizing two sequencing batch reactors (SBRs), PN1 and PN2 with different free ammonia (FA) concentrations, this study aimed to evaluate the NOB suppression strategy while enriching AOB. The PN2 reactor, which operated with a higher initial FA concentration (50 mg/L), successfully maintained high nitritation activity, with 96.1% ammonium removal efficiency (ARE) and 95.1% nitrite accumulation efficiency (NAE) at reduced influent NH4+-N concentrations (50 mg NH4+-N/L, FA 10 mg/L). In contrast, PN1 showed inadequate NOB suppression due to lower FA concentrations (10 mg/L). These results suggest that initiating the nitritation process with higher FA concentrations can effectively suppress NOB, enhancing the stability and efficiency of PN/A processes in mainstream applications.

Anaerobic ammonium oxidation (anammox)-based process has become a method for achieving carbon-neutral wastewater treatment. However, in mainstream wastewater with a low-strength ammonium, obtaining partial nitritation (PN) for the anammox process can be challenging and often result in NO3– accumulation. The recently proposed partial denitrification (PD), which reduces NO3– back to NO2–, can provide NO2– for anammox. For a successful PD-anammox (PD/A), it is crucial to efficiently cultivate PD bacteria (PDNB) and maintain a balance between the activities of PDNB and anammox bacteria (AnAOB). In this study, an efficient PDNB enrichment was cultivated for a long period of 400 days in a sequential batch reactor (SBR) by feeding it with acetate (300 mg COD/L) and nitrate (100 mg NO3–-N/L) at an exchange ratio of 50 %. The nitrite accumulation efficiency (NAE) gradually increased to >90 %, with Thauera phenylacetica identified as the key species for achieving high NAE. When PDNB was applied with AnAOB to remove 50 mg NH4+-N/L and 50 mg NO3–-N/L, different total nitrogen (TN) removal efficiencies were observed depending on the mixing ratio of PDNB and AnAOB (1:5–1:20). The most rapid and complete TN removal was achieved at the mixing ratio of 1:15. At lower mixing ratios of 1:5 and 1:10, PDNB activity exceeded that of AnAOB, resulting in incomplete TN removal. Conversely, at a higher inoculation ratio of 1:20, AnAOB activity surpassed of PDNB, leading to delayed T-N removal. These results indicate that maintaining a balance between NO2– accumulation by PDNB and NO2– consumption by AnAOB is essential for successful PD/A process operation. The findings of this study can be utilized as fundamental data for the operational strategy of an anammox-based process to achieve a carbon-neutral wastewater treatment.

Charcot–Marie–Tooth disease (CMT) is a hereditary disease with heterogeneous phenotypes and genetic causes. CMT type 1A (CMT1A) is a type of disease affecting the peripheral nerves and is caused by the duplication of the peripheral myelin protein 22 (PMP22) gene. Human tonsil-derived mesenchymal stem cells (TMSCs) are useful for stem cell therapy in various diseases and can be differentiated into Schwann cell-like cells (TMSC-SCs). We investigated the potential of TMSC-SCs called neuronal regeneration-promoting cells (NRPCs) for peripheral nerve and muscle regeneration in C22 mice, a model for CMT1A. We transplanted NRPCs manufactured in a good manufacturing practice facility into the bilateral thigh muscles of C22 mice and performed behavior and nerve conduction tests and histological and ultrastructural analyses. Significantly, the motor function was much improved, the ratio of myelinated axons was increased, and the G-ratio was reduced by the transplantation of NRPCs. The sciatic nerve and gastrocnemius muscle regeneration of C22 mice following the transplantation of NRPCs downregulated PMP22 overexpression, which was observed in a dose-dependent manner. These results suggest that NRPCs are feasible for clinical research for the treatment of CMT1A patients. Research applying NRPCs to other peripheral nerve diseases is also needed.

Increased hydrophobicity identified by the crystal structure presented in this work suggests a mechanism by which the S143F form of lamin A/C leads to progeria, a rapid aging syndrome. The authors observed aberrant molecular interactions that appear to lead to the nuclear deformation seen in other progeroid syndromes.

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease characterized by the deposition of amyloid-beta (Aβ) peptide and neurofibrillary tangles in the brain. The approved drug for AD has certain limitations such as a short period of cognitive improvement effect; moreover, the development of drug for AD therapeutic single target for Aβ clearance in brain ended in failure. Therefore, diagnosis and treatment of AD using a multi-target strategy according to the modulation of the peripheral system, which is not only limited to the brain, is needed. Traditional herbal medicines can be beneficial for AD based on a holistic theory and personalized treatment according to the time-order progression of AD. This literature review aimed to investigate the effectiveness of herbal medicine therapy based on syndrome differentiation, a unique theory of traditional diagnosis based on the holistic system, for multi-target and multi-time treatment of mild cognitive impairment or AD stage. Possible interdisciplinary biomarkers including transcriptomic and neuroimaging studies by herbal medicine therapy for AD were investigated. In addition, the mechanism by which herbal medicines affect the central nervous system in connection with the peripheral system in an animal model of cognitive impairment was reviewed. Herbal medicine may be a promising therapy for the prevention and treatment of AD through a multi-target and multi-time strategy. This review would contribute to the development of interdisciplinary biomarkers and understanding of the mechanisms of action of herbal medicine in AD.

Objectives:It is important to enrich and cultivate ammonia oxidation bacteria (AOB) in order to successfully treat nitrogen in high saline wastewater using a deammonification process. Two different inocula, a sewage sludge and a fish-market wastewater sludge, were cultivated to enrich AOB and compared the changes of microbial community. Methods:A sequential batch reactor (SBR) inoculated with the sewage sludge (PN1) enriched AOB under high-strength ammonium condition (500-3,000 mg NH4+-N/L) and then the salt concentration in the medium was gradually increased up to 20 g-NaCl/L. The other SBR seeded with the fish market wastewater sludge (PN2) was operated to enrich AOB directly under 20 g NaCl/L without any acclimation step. Results and Discussion:Both PN1 and PN2 successfully showed more than 60% of the nitrite accumulation efficiency at a high saline concentration of 20 g NaCl/L. At the level of the phylum, Proteobacteria containing nitrifying microorganisms became dominant in both PN1 and PN2. However, the most dominant bacterial species in PN1 and PN2 were Nitrosomonas eutropha (60.7%) and N. halophila (20.2%), respectively. Conclusions:Although different results of the most abundant AOB were shown in both sewage sludge and fish-market wastewater sludge conditions, nitritation was successfully developed even with wastewater containing high salinity. Therefore, in this study, both sludges can be applied for inoculation to the PN process for efficiently treating wastewater with high concentration of ammonium and saline.

The water-insoluble polyvinyl alcohol (PVA) nanofibers containing ZnO nanoparticles were prepared by an electrospinning technique for antiacne facial masks. Zinc oxide (ZnO) nanoparticles prepared by a sol-gel method were dispersed in aqueous PVA and citric acid solution for electrospinning. The electrospun nanofibers were treated at 160°C to induce the thermal crosslinking between PVA and citric acid. The crosslinked PVA with citric acid become water-insoluble, which can be used for facial masks. PVA/ZnO composite nanofibers were characterized by structural and morphological analysis techniques including Fourier transform infrared spectroscopy (FT-IR), field-emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM). Also, the swelling ratios according to the ZnO content (0, 1, 4, and 7 wt.% with respect to PVA) were measured. Antibacterial activity tests were also studied. The clear zone of Cutibacterium acnes of PVA/ZnO 7% nanofibers was 2.25 mm, indicating antiacne activities of nanofibers.

Abstract Background Due to the constraints surrounding autograft bone, surgeons have turned to osteoinductive agents to augment spinal fusion. Reports of complications and questionable efficacy slowed the adoption of these alternatives. Recombinant human platelet‐derived growth factor B homodimer (rhPDGF‐BB) has been Food and Drug Administration (FDA)‐approved (Augment) to promote fusion in other areas of orthopedics, but its characterization in spine fusion has not yet been tested. The purpose of this study is to characterize the host response to PDGF‐BB in vivo. Methods Eighty female Fischer rats underwent L4‐5 posterolateral fusion using one of four implant types: (a) iliac crest syngeneic allograft harvested from syngeneic donors, (b) β‐TCP/bovine collagen matrix (β‐TCP/Col) with sodium acetate buffer, (c) β‐TCP/Col with 0.3 mg/mL “low dose,” or (d) β‐TCP/Col with 3.0 mg/mL “high dose” of rhPDGF‐BB. Animals underwent magnetic resonance imaging (MRI) and serum cytokine quantification at 4, 7, 10, and 21 days, postoperatively. Tissues were processed for immunofluorescence staining for Ki67 and von Willebrand factor (vWF) to assess neovascularization. Results MRI demonstrated no differences in fluid accumulation among the four treatment groups at any of the time points. Serum cytokine analysis showed no clinically significant differences between treatment groups in 20 of the 27 cytokines. Inflammatory cytokines IFN‐γ, IL‐1β, IL‐18, MCP‐1, MIP‐1α, TNF‐α were not induced by rhPDGF‐BB. Histology showed no differences in cell infiltration, and Ki67 and vWF immunofluorescence staining was similar among groups. Conclusions rhPDGF‐BB delivered with a β‐TCP/Col matrix exerts no exaggerated systemic or local host inflammatory response when compared to iliac crest syngeneic allograft bone or the control carrier. rhPDGF‐BB mixed with a β‐TCP/Col matrix could be a viable and safe biologic alternative to syngeneic allograft in spine fusion. Further studies need to be performed to evaluate efficacy in this setting.

Alpha-synuclein (αSyn) is a major component of Lewy bodies, which are a known pathogenic marker of Parkinson's disease (PD). The dysfunction of protein degradation machinery causes αSyn accumulation. The reinforcement of αSyn degradation is a potential therapeutic target for PD because accumulated αSyn is responsible for the pathogenesis of PD. Nucleolin (NCL) is essential in the formation of the nucleolar structure. The function of NCL is correlated with oxidative stress-mediated cell death. A previous study demonstrated that NCL overexpression alleviated rotenone-induced neurotoxic effects, whereas knockdown of NCL had the opposite effect. These results suggest that NCL malfunction would exacerbate PD pathology. Thus, it was hypothesized that the introduction of ectopic NCL could rescue α-synucleinopathy in PD. This study investigated whether the ectopic expression of NCL facilitates αSyn clearance. Ectopic expression of NCL was accomplished via the transfection of green fluorescent protein (GFP) or GFP-NCL in mouse embryonic fibroblasts (MEF) or transduction of GFP or GFP-NCL using lentivirus in rat primary cortical neurons and mouse substantia nigra. NCL overexpression enhanced the clearance of accumulated or aggregated αSyn in MEFs and rat primary cortical neurons. The activity of the autophagy-lysosome pathway was enhanced by NCL expression. NCL transduction in the substantia nigra, which was co-injected with αSyn fibrils, rescued PD manifestation. The elevation of NCL levels may reflect a therapeutic strategy for α-synucleinopathy in PD.

Lamins are intermediate filaments and the major component of the nuclear lamina. Here the authors determine the crystal structure of a construct comprising the N-terminal half of human lamin A/C and use their structure and cross-linking and biochemical experiments to discuss lamin assembly.

Abstract Background Genipin is a compound derived from gardenia fruit extract. Although Genipin has anti-tumor effects in various cancers, its effect and mechanism in gastric cancer remain unclear. Here, we investigated the relationship between the anticancer effect of Genipin and signal transducer and activator of transcription (Stat3)/myeloid cell leukemia-1 (Mcl-1) in human gastric cancers. Methods MTT assays were performed to determine the cell viability of gastric cancer and gastric epithelial cell lines (AGS, MKN45, SNU638, MKN74, HFE-145). A TUNEL assay and Western blotting were carried out to investigate apoptosis. Stat3 activity was measured by proteome profiler phospho kinase array, immunofluorescence and immunoblotting. Mitochondria function was monitored with an XF24 analyzer and by flow cytometry, confocal microscopy using fluorescent probes for general mitochondrial membrane potential (MMP). Results Genipin induced apoptosis in gastric cancer cells, including AGS and MKN45 cells. Genipin also reduced Mcl-1 mRNA and protein levels. Furthermore, we found that phosphorylation of Stat3 is regulated by Genipin. Additionally, the protein level of phospho Janus kinase 2 (JAK2) was decreased by Genipin treatment, indicating that the Stat3/JAK2/Mcl-1 pathway is suppressed by Genipin treatment in gastric cancer cells. Mcl-1 is closely related to mitochondrial function. These findings suggest that Genipin contributes to the collapse of mitochondrial functions like MMP. Conclusions Genipin induced apoptosis by suppressing the Stat3/Mcl-1 pathway and led to mitochondrial dysfunction. Our results reveal a novel mechanism for the anti-cancer effect of Genipin in gastric cancer.

Anaerobic ammonium oxidation (anammox) is a biological nitrogen removal process with attractive prospects, such as no carbon addition, less aeration, lower greenhouse gas generation, and lower sludge production. However, it is difficult to maintain a stable anammox process since the anammox bacteria have a slow growth rate and high sensitivity to many factors. Therefore, it is very important to analyze and maintain the anammox activity as a process indicator for its successful operation. The conventional method for measuring the concentration of nitrogen compounds, such as ammonium, nitrite, or nitrogen gas is inconvenient during the reaction time for specific anammox activity (SAA) analysis, which can result in an inaccurately determined SAA due to the substrate loss and temperature change. In this study, a respirometer was utilized to analyze the SAA. The SAA values from a respirometer (rSAA) showed a similar pattern to the SAA values (mSAA) from the conventional method. All of the SAA analyses showed the highest value at 35 °C with a granule size of p-values for the t-test and Wilcoxon rank-sum test were >0.05. Therefore, the respirometer can be used as a simple and efficient tool for SAA analysis. Moreover, the operating maintenance and management of the anammox process can be improved due to the simple SAA analysis in the field.

Divalent cations were known to alleviate salinity stress on anammox bacteria. Understanding the mechanism of reducing the salinity stress on anammox granules is essential for the application of the anammox process for saline wastewater treatment. In this study, the effect of Ca2+ and Mg2+ augmentation on the recovery of the activity of freshwater anammox granules affected by salinity stress was evaluated. At the condition of a salinity stress of 5 g NaCl/L, the specific anammox activity (SAA) of the granule decreased to 50% of that of the SAA without NaCl treatment. Augmentation of Ca2+ at the optimum concentration of 200 mg/L increased the SAA up to 78% of the original activity, while the augmentation of Mg2+ at the optimum concentration of 70 mg/L increased the SAA up to 71%. EPS production in the granules was increased by the augmentation of divalent cations compared with the granules affected by salinity stress. In the soluble EPS, the ratio of protein to polysaccharides was higher in the granules augmented by Ca2+ than with Mg2+, and the functional groups of the EPS differed from each other. The amount of Na+ sequestered in the soluble EPS was increased by the augmentation of divalent cations, which seems to contribute to the alleviation of salinity stress. Ca. Kuenenia-like anammox bacteria, which were known to be salinity stress-tolerant, were predominant in the granules and there was no significant difference in the microbial community of the granules by the salinity stress treatment. Our results suggest that the alleviation effect of the divalent cations on the salinity stress on the anammox granules might be associated with the increased production of different EPS rather than in changes to the anammox bacteria.

Intermediate filaments (IFs) commonly have structural elements of a central α-helical coiled-coil domain consisting of coil 1a, coil 1b, coil 2, and their flanking linkers. Recently, the crystal structure of a long lamin A/C fragment was determined and showed detailed features of a tetrameric unit. The structure further suggested a new binding mode between tetramers, designated eA22, where a parallel overlap of coil 1a and coil 2 is the critical interaction. This study investigated the biochemical effects of genetic mutations causing human diseases, focusing on the eA22 interaction. The mutant proteins exhibited either weakened or augmented interactions between coil 1a and coil 2. The ensuing biochemical results indicated that the interaction requires the separation of the coiled-coils in the N-terminal of coil 1a and the C-terminal of coil 2, coupled with the structural transition in the central α-helical rod domain. This study provides insight into the role of coil 1a as a molecular regulator in the elongation of IF proteins.

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Oxidative stress is the most critical risk factor for neurodegenerative diseases, including Alzheimer’s disease (AD) and Huntington’s disease (HD). Numerous reports have demonstrated that oxidative stress aggravates cytotoxicity in dopaminergic neurons and accelerates the formation of protein inclusions. In addition, oxidative stress, such as 4-hydroxynonenal (HNE), oxidized protein, and dopamine quinone, are related to PD progression. DJ-1 is a PD-causative gene, and it plays a pivotal role as a sensor and eliminator of oxidative stress. Several studies have shown that oxidized DJ-1 (OxiDJ-1) formation is induced by oxidative stress. Hence, previous studies suggest that oxidized DJ-1 could be a biomarker for PD. We previously reported higher DJ-1 levels in Korean male PD patient urine exosomes than male non-PD controls. We speculate that OxiDJ-1 levels in PD patient urine might be higher than that in non-PD controls. In this study, we established an ELISA for OxiDJ-1 using recombinant DJ-1 treated with H2O2. Using Western blot assay and ELISA, we confirmed an increase of OxiDJ-1 from HEK293T cells treated with H2O2. Using our ELISA, we observed significantly higher, 2-fold, OxiDJ-1 levels in the urine of Korean PD patients than in non-PD controls.

Background: Although the anticancer activity of Korean Red Ginseng (KRG) has been known in various cancers, the mechanism of KRG-induced apoptosis is unknown in colorectal cancer (CRC). In our study, we examined whether KRG induces apoptosis in CRC cells. Methods: In the cell viability assay, the concentration of the appropriate KRG extracts was fixed at 2.5 mg/mL in numerous CRC cells. This fixed concentration was in other experiments, and it was confirmed that the KRG extracts induce apoptosis in CRC cells. Results: We found that KRG induced Noxa activation and apoptosis and increased endoplasmic reticulum stress via reactive oxygen species production. This indicated that KRG efficiently enhanced cell death in CRC cells. Conclusion: Our results show that KRG can be used as a possible anticancer drug for patients with CRC

Oxidative stress has been implicated in the pathogenesis of many diseases including chronic liver diseases. Nrf2 is a master transcriptional factor regulating the induction of cellular antioxidant defense systems. Here, the Nrf2-activating effect of the crude methanol extract of dried leaves of Pogostemon cablin Bentham was demonstrated by measuring the antioxidant response element (ARE)-driven luciferase activity and pachypodol, 4′,5-dihydroxy-3,3′,7-trimethoxyflavone, was isolated by bioactivity-guided fractionation and further separation using chromatographic techniques. To our knowledge, this is the first study to evaluate the antioxidant and cytoprotective effects of pachypodol in HepG2 cells as well as the underlying molecular mechanisms. Indeed, pachypodol protected HepG2 cells from cell death caused by tert-butylhydroperoxide-induced oxidative stress and also attenuated ROS production. The ability of pachypodol to activate Nrf2/ARE pathway was further confirmed by observing Nrf2 expression in nuclear fraction, mRNA levels of Nrf2 target antioxidants, and cellular glutathione content in HepG2 cells. Extracellular signal-regulated kinase (ERK) is one of the important kinases involved in Nrf2 activation. Pachypodol increased ERK phosphorylation and ERK inhibition by PD98059 totally abrogated the increase in ARE luciferase activity, nuclear Nrf2 accumulation and mRNA levels of antioxidant enzymes by pachypodol. In conclusion, pachypodol isolated from P. cablin can protect hepatocytes from oxidative injury, possibly mediated by enhancing endogenous antioxidant defense system through ERK-dependent Nrf2 activation.

Natural products have shown great promise in sensitizing cells to TNF-related apoptosis-inducing ligand (TRAIL) therapy. Sea cucumber (SC) extracts possess antitumor activity, and hence their potential to sensitize colorectal cancer (CRC) cells to TRAIL therapy was evaluated. This study used Western blotting to evaluate the combination effects of SC and TRAIL in CRC, and determined the molecular mechanism underlying these effects. SC fractions and TRAIL alone did not affect apoptosis; however, combined treatment dramatically induced the apoptosis of CRC cells, but not of normal colon cells. Combined treatment induced the expression of apoptotic proteins (poly (ADP-ribose) polymerase (PARP), caspase 3, and 8), and this effect was markedly inhibited by the ubiquitination of X-linked inhibitor of apoptosis protein (XIAP). SC did not affect the mRNA levels, but it increased proteasomal degradation and ubiquitination of the XIAP protein. Furthermore, SC induced reactive oxygen species (ROS) production, thereby activating c-Jun N-terminal kinase (JNK) and endoplasmic reticulum (ER) stress-related apoptotic pathways in CRC. Altogether, our results demonstrate that the SC F2 fraction may sensitize CRC cells to TRAIL-induced apoptosis through XIAP ubiquitination and ER stress.

Decomposition of lignin-related model compound (benzyl phenyl ether, BPE) to phenol and toluene was performed over carbon-supported noble metal (Ru, Pd, and Pt) catalysts in supercritical ethanol without supply of hydrogen. Phenol and toluene as target products were produced by the hydrogenolysis of BPE. The conversion of BPE was higher than 95% over all carbon-supported noble metal catalysts at 270 °C for 4 h. The 5 wt% Pd/C demonstrated the highest yield (ca. 59.3%) of the target products and enhanced conversion rates and reactivity more significantly than other catalysts. In the case of Ru/C, BPE was significantly transformed to other unidentified byproducts, more so than other catalysts. The Pt/C catalyst produced the highest number of byproducts such as alkylated phenols and gas-phase products, indicating that the catalyst promotes secondary reactions during the decomposition of BPE. In addition, a model reaction using phenol as a reactant was conducted to check the secondary reactions of phenol such as alkylation or hydrogenation in supercritical ethanol. The product distribution when phenol was used as a reactant was mostly consistent with BPE as a reactant. Based on the results, plausible reaction pathways were proposed.

The inhibition of bone healing in humans is a well-established effect associated with cigarette smoking, but the underlying mechanisms are still unclear. Recent work using animal cell lines have implicated the aryl hydrocarbon receptor (AhR) as a mediator of the anti-osteogenic effects of cigarette smoke, but the complexity of cigarette smoke mixtures makes understanding the mechanisms of action a major challenge. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin) is a high-affinity AhR ligand that is frequently used to investigate biological processes impacted by AhR activation. Since there are dozens of AhR ligands present in cigarette smoke, we utilized dioxin as a prototype ligand to activate the receptor and explore its effects on pro-osteogenic biomarkers and other factors critical to osteogenesis using a human osteoblast-like cell line. We also explored the capacity for AhR antagonists to protect against dioxin action in this context. We found dioxin to inhibit osteogenic differentiation, whereas co-treatment with various AhR antagonists protected against dioxin action. Dioxin also negatively impacted cell adhesion with a corresponding reduction in the expression of integrin and cadherin proteins, which are known to be involved in this process. Similarly, the dioxin-mediated inhibition of cell migration correlated with reduced expression of the chemokine receptor CXCR4 and its ligand, CXCL12, and co-treatment with antagonists restored migratory capacity. Our results suggest that AhR activation may play a role in the bone regenerative response in humans exposed to AhR activators, such as those present in cigarette smoke. Given the similarity of our results using a human cell line to previous work done in murine cells, animal models may yield data relevant to the human setting. In addition, the AhR may represent a potential therapeutic target for orthopedic patients who smoke cigarettes, or those who are exposed to secondhand smoke or other environmental sources of aryl hydrocarbons.

Nuclear lamins maintain the nuclear envelope structure by forming long linear filaments via two alternating molecular arrangements of coiled-coil dimers, known as A11 and A22 binding modes. The A11 binding mode is characterized by the antiparallel interactions between coil 1b domains, whereas the A22 binding mode is facilitated by interactions between the coil 2 domains of lamin. The junction between A11- and A22-interacting dimers in the lamin tetramer produces another parallel head--tail interaction between coil 1a and the C-terminal region of coil 2, called the ACN interaction. During mitosis, phosphorylation in the lamin N-terminal head region by the cyclin-dependent kinase (CDK) complex triggers depolymerization of lamin filaments, but the associated mechanisms remain unknown at the molecular level. In this study, we revealed using the purified proteins that phosphorylation by the CDK1 complex promotes disassembly of lamin filaments by directly abolishing the ACN interaction between coil 1a and the C-terminal portion of coil 2. We further observed that this interaction was disrupted as a result of alteration of the ionic interactions between coil 1a and coil 2. Combined with molecular modeling, we propose a mechanism for CDK1-dependent disassembly of the lamin filaments. Our results will help to elucidate the cell cycle--dependent regulation of nuclear morphology at the molecular level. [ABSTRACT FROM AUTHOR]