A Caring Program for Health Promotion among Women Who Have Experienced Trauma: A QuasiExperimental Pilot Study

Purpose@#Women are more vulnerable to post-traumatic stress (PTS) than men, causing several health problems. Nurses should understand and work with women who have experienced trauma and provide interventions to promote their physical, social, and mental health. @*Methods@#This quasi-experimental pilot study used a one-group pre-test/post-test design. Data were collected from 14 women recruited between December 2019 and May 2020 from a self-sufficiency support center in South Korea for sexually-exploited women who had experienced trauma. The program consisted of six one-on-one intervention sessions per week for six weeks. Each session averaged 60~120 minutes. Participants were assessed at pre-test, post-test, and one-month follow-up. Changes in outcome variables over time were analyzed using the Wilcoxon signed-rank and Friedman tests. @*Results@#The caring program for health promotion was divided into six sessions: understanding the self, sharing traumatic events and negative emotions, reframing the meaning of traumatic events, identifying thoughts and physical and emotional responses, developing health promotion activities, and maintaining a positive attitude during the process of change. As a result of the caring program, PTS (F = 36.33, p < .001), depression (F = 24.45, p < .001), health-promoting behaviors (F = 7.06, p = .004), and self-esteem (F = 19.74, p < .001) among the participants differed significantly at pre-test, post-test, and follow-up. @*Conclusion@#This study provides foundational information for the implementation of a theory-driven program by nurses in clinical and community settings to provide comprehensive care for women who have experienced trauma.

The elderly population are more vulnerable for the management of colorectal cancer during the COVID-19 pandemic: a nationwide, population-based study

Background/Aims@#The impact of coronavirus disease 2019 (COVID-19) on the management of colorectal cancer (CRC) may worse in elderly population, as almost all COVID-19 deaths occurred in the elderly patients. This study aimed to evaluate the impact of COVID-19 on CRC management in the elderly population. @*Methods@#The numbers of patients who underwent colonoscopy, who visited hospitals or operated for CRC in 2020 and 2021 (COVID-19 era) were compared with those in 2019, according to 3 age groups (≥70 years, 50–69 years, and ≤49 years), based on the nationwide, population-based database (2019–2021) in South Korea. @*Results@#The annual volumes of colonoscopy and hospital visits for CRC in 2020 were more significantly declined in the old age group than in the young age group (both P<0.001). In addition, the annual volume of patients operated for CRC numerically more declined in old age group than in young age group. During the first surge of COVID-19 (March and April 2020), old age patients showed statistically significant declines for the monthly number of colonoscopies (–46.5% vs. –39.3%, P<0.001), hospital visits (–15.4% vs. –7.9%, P<0.001), CRC operations (–33.8% vs. –0.7%, P<0.05), and colonoscopic polypectomies (–41.8% vs. –38.0%, P<0.001) than young age patients, compared with those of same months in 2019. @*Conclusions@#Elderly population are more vulnerable for the management of CRC during the COVID-19 pandemic. Therefore, the elderly population are more carefully cared for in the management of CRC during the next pandemic.

Reduced Cytotoxicity by Repetitive mRNA Transfection in Differentiated Neurons

Background and Objectives@#mRNA-based protein expression technology has been used to express functional proteins. We have previously generated dopamine neurons from rat-embryo derived neural precursor cells (NPCs) through repeated transfection of synthetic transcription factor mRNA encoding dopamine-inducible genes. However, NPCs began to die approximately 10 d post-transfection. In this study, we examined a long-term transfection protocol that did not affect cell viability. @*Methods@#and Results: Experiments were performed in eight groups sorted according to the start date of mRNA transfection. mRNA was transfected into NPCs daily for 21 d and live cell images of each group were recorded. NPCs which were differentiated for more than five days showed sustained gene expression and appreciable viability despite daily mRNA transfection for 21 d. @*Conclusions@#Repeated mRNA transfection requires cells with a sufficient differentiation period.

Immunomodulatory Effect of Epidermal Growth Factor Secreted by Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells on Atopic Dermatitis

Background and Objectives@#Human mesenchymal stem cells (MSCs) are emerging as a treatment for atopic dermatitis (AD), a chronic inflammatory skin disorder that affects a large number of people across the world. Treatment of AD using human umbilical cord blood-derived MSCs (hUCB-MSCs) has recently been studied. However, the mechanism underlying their effect needs to be studied continuously. Thus, the objective of this study was to investigate the immunomodulatory effect of epidermal growth factor (EGF) secreted by hUCB-MSCs on AD. @*Methods@#and Results: To explore the mechanism involved in the therapeutic effect of MSCs for AD, a secretome array was performed using culture medium of hUCB-MSCs. Among the list of genes common for epithelium development and skin diseases, we focused on the function of EGF. To elucidate the effect of EGF secreted by hUCB-MSCs, EGF was downregulated in hUCB-MSCs using EGF-targeting small interfering RNA. These cells were then co-cultured with keratinocytes, Th2 cells, and mast cells. Depletion of EGF disrupted immunomodulatory effects of hUCB-MSCs on these AD-related inflammatory cells. In a Dermatophagoides farinae-induced AD mouse model, subcutaneous injection of hUCB-MSCs ameliorated gross scoring, histopathologic damage, and mast cell infiltration. It also significantly reduced levels of inflammatory cytokines including interleukin (IL)-4, tumor necrosis factor (TNF)-α, thymus and activation-regulated chemokine (TARC), and IL-22, as well as IgE levels. These therapeutic effects were significantly attenuated at all evaluation points in mice injected with EGF-depleted hUCB-MSCs. @*Conclusions@#EGF secreted by hUCB-MSCs can improve AD by regulating inflammatory responses of keratinocytes, Th2 cells, and mast cells.

Combined Mesenchymal Stem Cells and Cartilage Acellular Matrix Injection Therapy for Osteoarthritis in Goats

Background@#Human umbilical cord blood-derived MSCs (hUCB-MSCs) have been studied in osteoarthritis (OA) and cartilage regeneration. Our previous study demonstrated that hUCB-MSCs combined with cartilage acellular matrix injection (CAM Inj.) represent potential therapeutic agents for structural improvement and anti-inflammatory effects in a rabbit model of OA. @*Methods@#Based on a previous study, this study has evaluated the safety and efficacy of hUCB-MSCs combined with CAM Inj. in an anterior cruciate ligament transection (ACLT) with medial meniscectomy (MMx) in a goat model. In this study, 27 goats were divided into 5 groups: normal (n = 3), OA (n = 6), OA + CAM Inj. (n = 6), OA + hUCB-MSCs (n = 6), and OA + hUCB-MSCs + CAM Inj. (n = 6). Lameness and radiographic parameters were assessed 6 months after administration, and macroscopic and histological evaluations of the goat articular cartilage were performed 6 months after intervention. @*Results@#The results showed significant improvement in lameness score only in the OA + hUCB-MSCs group at 5 months after treatment (*p < 0.05), whereas the K&L score showed significant improvement only in the OA + hUCB-MSCs + CAM Inj. group 6 months after intervention (*p< 0.05). In addition, the gross findings showed significance in OA + CAM Inj. and OA + hUCB-MSCs + CAM Inj. groups 6 months after treatment (*,p < 0.05 and **p < 0.01). @*Conclusion@#In conclusion, treatment with a combination of hUCB-MSCs and CAM Inj. reduced OA symptoms and induced effective cartilage tissue repair in a goat model. We suggest the combination of hUCB-MSCs and CAM Inj. as an alternative therapy for OA.

Generation of Cortical Brain Organoid with Vascularization by Assembling with Vascular Spheroid

Background and Objectives@#Brain organoids have the potential to improve our understanding of brain development and neurological disease. Despite the importance of brain organoids, the effect of vascularization on brain organoids is largely unknown. The objective of this study is to develop vascularized organoids by assembling vascular spheroids with cerebral organoids. @*Methods@#and Results: In this study, vascularized spheroids were generated from non-adherent microwell culture system of human umbilical vein endothelial cells, human dermal fibroblasts and human umbilical cord blood derived mesenchymal stem cells. These vascular spheroids were used for fusion with iPSCs induced cerebral organoids. Immunostaining studies of vascularized organoids demonstrated well organized vascular structures and reduced apoptosis. We showed that the vascularization in cerebral organoids up-regulated the Wnt/β-catenin signaling. @*Conclusions@#We developed vascularized cerebral organoids through assembly of brain organoids with vascular spheroids. This method could not only provide a model to study human cortical development but also represent an opportunity to explore neurological disease.

Upper Extremity Deep Vein Thrombosis After Botulinum Toxin Injection: A Case Report

Botulinum toxin (BoNT) injection is widely used to improve spasticity. However, after the treatment, the patient may experience pain, inflammation, swelling and redness at the injection site. In this case, we addressed deep vein thrombosis (DVT) after BoNT treatment of the upper limb. A male aged 37 years had spasticity and dystonia in his left upper extremity. BoNT-A 100 U was injected into the left biceps brachii and an equal amount into the brachialis to relieve spasticity. After three days, he developed redness and painful swelling in the left upper arm and the next day, through the upper extremity computed tomography venography, DVT was identified in the left cephalic vein. The thrombus resolved after the anticoagulation therapy with rivaroxaban (Xarelto). We hypothesized the role of mainly three mechanisms in the development of DVT in this case: repetitive strenuous activity, relative stasis due to reduced muscle tone, and possible direct mechanical damage to the vessel wall.

Effect of pregabalin on nociceptive thresholds and immune responses in a mouse model of incisional pain

Background@#It is known that some analgesics as well as pain can affect the immune system. The aim of this study was to investigate the analgesic effect and immunomodulation of pregabalin (PGB) in a mouse incisional pain model. @*Methods@#A postoperative pain model was induced by hind paw plantar incision in male BALB/c mice. Mice were randomly divided into four groups (n = 8): a salinetreated incision (incision), PGB-treated incision (PGB-incision), sham controls without incision or drug treatment (control), and a PGB-treated control (PGB-control).In the PGB treated groups, PGB was administered intraperitoneally (IP) 30 minutes before and 1 hour after the plantar incision. Changes of the mechanical nociceptive thresholds following incision were investigated. Mice were euthanized for spleen harvesting 12 hours after the plantar incision, and natural killer (NK) cytotoxicity to YAC 1 cells and lymphocyte proliferation responses to phytohemagglutinin were compared among these four groups. @*Results@#Mechanical nociceptive thresholds were decreased after plantar incision and IP PGB administration recovered these decreased mechanical nociceptive thresholds (P < 0.001). NK activity was increased by foot incision, but NK activity in the PGB-incision group was significantly lower than that in the Incision group (P < 0.001). Incisional pain increased splenic lymphocyte proliferation, but PGB did not alter this response. @*Conclusions@#Incisional pain alters cell immunity of the spleen in BALB/c mice. PGB showed antinocieptive effect on mouse incisional pain and attenuates the activation of NK cells in this painful condition. These results suggest that PGB treatment prevents increases in pain induced NK cell activity.

Serum interferon-γ and urinary monocyte chemoattractant peptide-1 are important factors in the pathogenesis of immunoglobulin A nephropathy

Background@#Imbalance of T helper (Th) 1/2 cells has been shown to contribute to the development of immunoglobulin A nephropathy (IgAN). To address the inconsistent results on the role of Th1/Th2 polarization, we evaluated the levels of Th1/Th2 cytokines in various samples from patients with IgAN. @*Methods@#Thirty-one patients with biopsy-proven IgAN (age, 34.48 ± 12.10 years) and 25 healthy controls (age, 44.84 ± 13.72 years) were enrolled. We evaluated the relationship between the levels of Th1/Th2 cytokines and the response to glucocorticoid treatment. @*Results@#The levels of serum interferon-gamma (IFNγ) and urinary monocyte chemoattractant peptide (MCP)-1 were higher in the IgAN group than in the control group. The levels of MCP-1 in urine and secreted by peripheral blood mononuclear cells (PBMCs) were significantly different among three groups categorized based on daily proteinuria. The level of urinary MCP-1 was significantly correlated with proteinuria. The levels of urinary MCP-1, serum interleukin (IL)-4, IFNγ, and IL-2 secreted by PBMCs and intrarenal IL-1 messenger RNA (mRNA) were significantly correlated with the ratio of proteinuria at 6 months to baseline proteinuria in patients undergoing glucocorticoid treatment. MCP-1 mRNA and protein levels were significantly upregulated in mesangial cells stimulated with IFNγ among representative Th1/Th2 cytokines. @*Conclusion@#IFNγ was shown to be a key cytokine in the pathogenic processes underlying IgAN, and its upregulation induced an increase in urinary MCP-1 production. These findings suggest that Th1 cytokines may play an important role in the development of IgAN.

Upper Extremity Deep Vein Thrombosis After Botulinum Toxin Injection: A Case Report

Botulinum toxin (BoNT) injection is widely used to improve spasticity. However, after the treatment, the patient may experience pain, inflammation, swelling and redness at the injection site. In this case, we addressed deep vein thrombosis (DVT) after BoNT treatment of the upper limb. A male aged 37 years had spasticity and dystonia in his left upper extremity. BoNT-A 100 U was injected into the left biceps brachii and an equal amount into the brachialis to relieve spasticity. After three days, he developed redness and painful swelling in the left upper arm and the next day, through the upper extremity computed tomography venography, DVT was identified in the left cephalic vein. The thrombus resolved after the anticoagulation therapy with rivaroxaban (Xarelto). We hypothesized the role of mainly three mechanisms in the development of DVT in this case: repetitive strenuous activity, relative stasis due to reduced muscle tone, and possible direct mechanical damage to the vessel wall.

Induced neural stem cells from human patient-derived fibroblasts attenuate neurodegeneration in Niemann-Pick type C mice

Background@#Niemann-Pick disease type C (NPC) is caused by the mutation of NPC genes, which leads to the abnormal accumulation of unesterified cholesterol and glycolipids in lysosomes. This autosomal recessive disease is characterized by liver dysfunction, hepatosplenomegaly, and progressive neurodegeneration. Recently, the application of induced neural stem cells (iNSCs), converted from fibroblasts using specific transcription factors, to repair degenerated lesions has been considered a novel therapy. @*Objectives@#The therapeutic effects on NPC by human iNSCs generated by our research group have not yet been studied in vivo; in this study, we investigate those effects. @*Methods@#We used an NPC mouse model to efficiently evaluate the therapeutic effect of iNSCs, because neurodegeneration progress is rapid in NPC. In addition, application of human iNSCs from NPC patient-derived fibroblasts in an NPC model in vivo can give insight into the clinical usefulness of iNSC treatment. The iNSCs, generated from NPC patientderived fibroblasts using the SOX2 and HMGA2 reprogramming factors, were transplanted by intracerebral injection into NPC mice. @*Results@#Transplantation of iNSCs showed positive results in survival and body weight change in vivo. Additionally, iNSC-treated mice showed improved learning and memory in behavior test results. Furthermore, through magnetic resonance imaging and histopathological assessments, we observed delayed neurodegeneration in NPC mouse brains. @*Conclusions@#iNSCs converted from patient-derived fibroblasts can become another choice of treatment for neurodegenerative diseases such as NPC.

Usefulness of Diffusion Tensor Imaging in Unexplained Ipsilateral Hemiplegia / 대한신경손상학회지

Ipsilateral hemiparesis is a rare and challenging sign in clinical neurological practice.Although the etiology of this manifestation is poorly understood, recent studies have attempted to probe the pathomechanism of this sign with advanced radiological techniques.Additional knowledge about the lesion and unraveling the pathomechanisms causing neurological impairments are important to predict the prognosis and clinical course and to aid in rehabilitation. Therefore, we present a case of a patient with a traumatic subdural hematoma on the left hemisphere and left spastic hemiparesis. Using diffusion tensor imaging (DTI), we concluded that the right corticospinal tract injury caused by compression of the cerebral peduncle accounted for the ipsilateral hemiparesis, also known as Kernohan's notch phenomenon. Thus, this case report highlights the usefulness of the newer radiological techniques, such as DTI, to identify the pathomechanisms of neurological presentations.

Effect of pregabalin on nociceptive thresholds and immune responses in a mouse model of incisional pain

Background@#It is known that some analgesics as well as pain can affect the immune system. The aim of this study was to investigate the analgesic effect and immunomodulation of pregabalin (PGB) in a mouse incisional pain model. @*Methods@#A postoperative pain model was induced by hind paw plantar incision in male BALB/c mice. Mice were randomly divided into four groups (n = 8): a salinetreated incision (incision), PGB-treated incision (PGB-incision), sham controls without incision or drug treatment (control), and a PGB-treated control (PGB-control).In the PGB treated groups, PGB was administered intraperitoneally (IP) 30 minutes before and 1 hour after the plantar incision. Changes of the mechanical nociceptive thresholds following incision were investigated. Mice were euthanized for spleen harvesting 12 hours after the plantar incision, and natural killer (NK) cytotoxicity to YAC 1 cells and lymphocyte proliferation responses to phytohemagglutinin were compared among these four groups. @*Results@#Mechanical nociceptive thresholds were decreased after plantar incision and IP PGB administration recovered these decreased mechanical nociceptive thresholds (P < 0.001). NK activity was increased by foot incision, but NK activity in the PGB-incision group was significantly lower than that in the Incision group (P < 0.001). Incisional pain increased splenic lymphocyte proliferation, but PGB did not alter this response. @*Conclusions@#Incisional pain alters cell immunity of the spleen in BALB/c mice. PGB showed antinocieptive effect on mouse incisional pain and attenuates the activation of NK cells in this painful condition. These results suggest that PGB treatment prevents increases in pain induced NK cell activity.

Serum interferon-γ and urinary monocyte chemoattractant peptide-1 are important factors in the pathogenesis of immunoglobulin A nephropathy

Background@#Imbalance of T helper (Th) 1/2 cells has been shown to contribute to the development of immunoglobulin A nephropathy (IgAN). To address the inconsistent results on the role of Th1/Th2 polarization, we evaluated the levels of Th1/Th2 cytokines in various samples from patients with IgAN. @*Methods@#Thirty-one patients with biopsy-proven IgAN (age, 34.48 ± 12.10 years) and 25 healthy controls (age, 44.84 ± 13.72 years) were enrolled. We evaluated the relationship between the levels of Th1/Th2 cytokines and the response to glucocorticoid treatment. @*Results@#The levels of serum interferon-gamma (IFNγ) and urinary monocyte chemoattractant peptide (MCP)-1 were higher in the IgAN group than in the control group. The levels of MCP-1 in urine and secreted by peripheral blood mononuclear cells (PBMCs) were significantly different among three groups categorized based on daily proteinuria. The level of urinary MCP-1 was significantly correlated with proteinuria. The levels of urinary MCP-1, serum interleukin (IL)-4, IFNγ, and IL-2 secreted by PBMCs and intrarenal IL-1 messenger RNA (mRNA) were significantly correlated with the ratio of proteinuria at 6 months to baseline proteinuria in patients undergoing glucocorticoid treatment. MCP-1 mRNA and protein levels were significantly upregulated in mesangial cells stimulated with IFNγ among representative Th1/Th2 cytokines. @*Conclusion@#IFNγ was shown to be a key cytokine in the pathogenic processes underlying IgAN, and its upregulation induced an increase in urinary MCP-1 production. These findings suggest that Th1 cytokines may play an important role in the development of IgAN.

Inhibitory effect of the probiotic bacteria, Weissella cibaria CMU on halitosis: a randomized placebo-controlled study / 대한구강보건학회지

Objectives@#Previous studies have suggested that the lactic acid bacterium, Weissella cibaria CMU has beneficial effects on halitosis, but its precise effects have not been evaluated in human subjects. We evaluated the efficacy and safety of W. cibaria CMU for reducing halitosis in adults (20-70 years old) whose exhibited volatile sulfur compound (VSC) concentrations exceeded 0.015 ng/mL and who scored ≥2 points in a halitosis sensory evaluation test. @*Methods@#A total of 60 participants were assigned to an experimental group (treated with W. cibaria CMU) and a control group (placebo). In total, 58 out of 60 participants (experimental group, 29; control group, 29) were ultimately included in gas chromatography (OralChroma) analyses of VSC concentrations and halitosis sensory evaluation tests. @*Results@#We found that the VSC concentration decreased by 0.030±0.062 ng/ml in the experimental group after 8 weeks (P=0.0138) and increased by 0.005±0.124 ng/ml in the control group (P=0.8198). However, the difference between groups was not statistically significant (P>0.05). In a sensory evaluation test, a significantly lower score was obtained for the experimental group than for the control group. @*Conclusions@#Overall, VSC concentrations and sensory evaluation scores were lower in the experimental group than in the control group, but only the latter was statistically significant. Thus, we conclude that W. cibaria CMU is involved in the reduction of halitosis.

Delphinidin enhances radio-therapeutic effects via autophagyinduction and JNK/MAPK pathway activation in non-small celllung cancer

Delphinidin is a major anthocyanidin compound found in various vegetablesand fruits. It has anti-oxidant, anti-inflammatory, and various other biologicalactivities. In this study we demonstrated the anti-cancer activity of delphinidin,which was related to autophagy, in radiation-exposed non-small cell lung cancer(NSCLC). Radiosensitising effects were assessed in vitro by treating cells with a subcytotoxicdose of delphinidin (5 M) before exposure to -ionising radiation (IR). Wefound that treatment with delphinidin or IR induced NSCLC cell death in vitro; howeverthe combination of delphinidin pre-treatment and IR was more effective thaneither agent alone, yielding a radiation enhancement ratio of 1.54 at the 50% lethaldose. Moreover, combined treatment with delphinidin and IR, enhanced apoptoticcell death, suppressed the mTOR pathway, and activated the JNK/MAPK pathway.Delphinidin inhibited the phosphorylation of PI3K, AKT, and mTOR, and increasedthe expression of autophagy-induced cell death associated-protein in radiation-exposedNSCLC cells. In addition, JNK phosphorylation was upregulated by delphinidinpre-treatment in radiation-exposed NSCLC cells. Collectively, these results show thatdelphinidin acts as a radiation-sensitizing agent through autophagy induction andJNK/MAPK pathway activation, thus enhancing apoptotic cell death in NSCLC cells.

Inhibitory effect of the probiotic bacteria, Weissella cibaria CMU on halitosis: a randomized placebo-controlled study / 대한구강보건학회지

Objectives@#Previous studies have suggested that the lactic acid bacterium, Weissella cibaria CMU has beneficial effects on halitosis, but its precise effects have not been evaluated in human subjects. We evaluated the efficacy and safety of W. cibaria CMU for reducing halitosis in adults (20-70 years old) whose exhibited volatile sulfur compound (VSC) concentrations exceeded 0.015 ng/mL and who scored ≥2 points in a halitosis sensory evaluation test. @*Methods@#A total of 60 participants were assigned to an experimental group (treated with W. cibaria CMU) and a control group (placebo). In total, 58 out of 60 participants (experimental group, 29; control group, 29) were ultimately included in gas chromatography (OralChroma) analyses of VSC concentrations and halitosis sensory evaluation tests. @*Results@#We found that the VSC concentration decreased by 0.030±0.062 ng/ml in the experimental group after 8 weeks (P=0.0138) and increased by 0.005±0.124 ng/ml in the control group (P=0.8198). However, the difference between groups was not statistically significant (P>0.05). In a sensory evaluation test, a significantly lower score was obtained for the experimental group than for the control group. @*Conclusions@#Overall, VSC concentrations and sensory evaluation scores were lower in the experimental group than in the control group, but only the latter was statistically significant. Thus, we conclude that W. cibaria CMU is involved in the reduction of halitosis.

Cdo Is Required for Efficient Motor Neuron Generation of Embryonic Stem Cells

Background and Objectives@#The directed differentiation of pluripotent stem cells into motor neurons is critical for the development of disease modelling and therapeutics to intervene degenerative motor neuron diseases. Cell surface receptor Cdo functions as a coreceptor for Sonic hedgehog (Shh) with Boc and Gas1 in the patterning of ventral spinal cord neurons including motor neurons. However, the discrete function of Cdo is not fully understood. @*Methods@#and Results: In this study, we examined the role of Cdo in motor neuron generation by utilizing in vitro differentiation of Cdo＋/＋ and Cdo−/− embryonic stem cells (ESCs). In response to Shh, Cdo−/− ESCs exhibited impaired expression of motor neuron specification markers while dorsal interneuron specification markers were significantly increased, compared to Cdo＋/＋ ESCs. Reactivation of Shh signalling pathway with Smoothened (Smo) agonist (SAG) restored motor neuron specification in Cdo−/− ESCs. In addition, electrophysiological analysis revealed the immature electrical features of Cdo−/− ESCs-derived neurons which was restored by SAG. @*Conclusions@#Taken together, these data suggest that Cdo as a Shh coreceptor is required for the induction of motor neuron generation by fully activating Shh signalling pathway and provide additional insights into the biology of motor neuron development.

Delphinidin enhances radio-therapeutic effects via autophagyinduction and JNK/MAPK pathway activation in non-small celllung cancer

Delphinidin is a major anthocyanidin compound found in various vegetablesand fruits. It has anti-oxidant, anti-inflammatory, and various other biologicalactivities. In this study we demonstrated the anti-cancer activity of delphinidin,which was related to autophagy, in radiation-exposed non-small cell lung cancer(NSCLC). Radiosensitising effects were assessed in vitro by treating cells with a subcytotoxicdose of delphinidin (5 M) before exposure to -ionising radiation (IR). Wefound that treatment with delphinidin or IR induced NSCLC cell death in vitro; howeverthe combination of delphinidin pre-treatment and IR was more effective thaneither agent alone, yielding a radiation enhancement ratio of 1.54 at the 50% lethaldose. Moreover, combined treatment with delphinidin and IR, enhanced apoptoticcell death, suppressed the mTOR pathway, and activated the JNK/MAPK pathway.Delphinidin inhibited the phosphorylation of PI3K, AKT, and mTOR, and increasedthe expression of autophagy-induced cell death associated-protein in radiation-exposedNSCLC cells. In addition, JNK phosphorylation was upregulated by delphinidinpre-treatment in radiation-exposed NSCLC cells. Collectively, these results show thatdelphinidin acts as a radiation-sensitizing agent through autophagy induction andJNK/MAPK pathway activation, thus enhancing apoptotic cell death in NSCLC cells.

Weissella cibaria CMU suppresses mgl gene expression and enzyme activity associated with bad breath

The oral care probiotic strain Weissella cibaria CMU (oraCMU) inhibits volatile sulphur compounds associated with halitosis, presumably by inhibiting the growth of associated oral pathogens. In the present study, we investigated whether oraCMU inhibits the production of these compounds by suppressing the expression of mgl. This gene encodes L-methionine-α-deamino-γ-mercaptomethane-lyase (METase) and is involved in the production of methyl mercaptan (CH₃SH) by Porphyromonas gingivalis. Therefore, we specifically investigated the effects of oraCMU on the growth, CH₃SH production, METase activity, and mgl expression of P. gingivalis. The minimum inhibitory concentrations of cell-free supernatant and secreted proteins from oraCMU were 125 mg/mL and 800 µg/mL, respectively. At sub-minimum inhibitory concentration levels, these metabolites inhibited CH₃SH production, but they also reduced P. gingivalis viability. Only heat-killed oraCMU decreased CH₃SH production without affecting P. gingivalis viability. Heat-killed oraCMU also inhibited METase activity toward L-methionine and mgl mRNA expression (p < 0.05). In summary, we demonstrated the inhibition of volatile sulphur compounds via the antimicrobial action of oraCMU and, for the first time, the inhibition of such compounds by heat-killed oraCMU, which occurred at the molecular level.