Evaluation of the value of Synechococcus 7942 as a sensitizer for photo-sonodynamic therapy against breast cancer.

This study was conducted to investigate the value of Synechococcus 7942 (Syne) as a sensitizer for photo-sonodynamic therapy (PSDT). Syne was characterized. The efficacy of Syne-mediated PSDT were verified in vitro (in 4T1 breast cancer cells) and in vivo (in a breast tumor-bearing mouse model). The safety of Syne-mediated PSDT was verified in vivo. Results indicated that Syne triggered the generation of oxygen and ROS during PSDT, thereby inducing cell death in 4T1 cells. Syne-mediated PSDT induced the death of tumor cells both in vitro and in vivo. The speed of tumor growth was delayed in animals receiving PSDT. Syne-mediated PSDT was more effective than photodynamic therapy or sonodynamic therapy alone. In addition, administration of a Syne monomer resulted in satisfactory tumor targeting. Syne-mediated PSDT affected neither the animal body weight nor the major organs, indicating satisfactory safety. Accordingly, Syne is an efficient, safe, and readily available sensitizer that is ideal for potential clinical use of PSDT to treat breast cancer. The findings of this study are useful for exploration of a novel sensitizer for PSDT, which might be a promising alternative therapy against breast cancer.

α-synuclein regulates Cyclin D1 to promote abnormal initiation of the cell cycle and induce apoptosis in dopamine neurons.

The etiology of Parkinson's disease (PD) is characterized by the death of dopamine neurons in the substantia nigra pars compacta, while misfolding and abnormal aggregation of α-synuclein (α-syn) are core pathological features. Previous studies have suggested that damage to dopamine neurons may be related to cell cycle dysregulation, but the specific mechanisms remain unclear. In this study, a PD mouse model was induced by stereotactic injection of α-syn into the nucleus, and treated with the cell cycle inhibitor, roscovitine (Rosc). The results demonstrated that Rosc improved behavioral disorders caused by α-syn, increased TH protein expression, inhibited α-syn and p-α-syn protein expression, and reduced the expression levels of G1/S phase cell cycle genes Cyclin D1, Cyclin E, CDK2, CDK4, E2F and pRB. Additionally, Rosc decreased Bax and Caspase-3 expression caused by α-syn, while increasing Bcl-2 protein expression. Meanwhile, we observed that α-syn can influence neuronal cell autophagy by decreasing the expression level of Beclin 1 and increasing the expression level of P62. However, Rosc can improve this phenomenon. In a cell model induced by α-syn in dopamine neuron injury cells, knockdown of Cyclin D1 led to similar results as those observed in animal experiments: Knocking down Cyclin D1 improved the abnormal initiation of the cell cycle caused by α-syn and regulated cellular autophagy, resulting in a reduction of apoptosis in dopamine neurons. In summary, exogenous α-syn can lead to the accumulation of α-syn and phosphorylated α-syn in dopamine neurons, increase key factors of the G1/S phase cell cycle such as Cyclin D1, and regulate downstream related indicators, causing the cell cycle to restart and leading to apoptosis of dopamine neurons. This exacerbates PD symptoms. However, knockdown of Cyclin D1 inhibits the progression of the cell cycle and can reverse this situation. These findings suggest that a Cyclin D inhibitor may be a novel therapeutic target for treating PD.

Multidisciplinary treatment of advanced cervical esophageal adenocarcinoma derived from a gastric inlet patch: A case report.

A gastric inlet patch (GIP) is an ectopic gastric mucosal lesion usually arising at the cervical esophagus that may rarely cause esophageal adenocarcinoma (EAC). To the best of our knowledge, this is the first case of a GIP-derived EAC that was successfully treated using a multidisciplinary treatment approach. A 64-year-old man was referred to the Department of Gastrointestinal Surgery, Kanazawa University Hospital (Kanazawa, Japan) for surgical treatment of refractory recurrent cervical EAC derived from GIP who had previously been treated with induction chemotherapy, definitive chemoradiotherapy and photodynamic therapy (PDT). Esophagogastroduodenoscopy revealed a stenotic tumor at the GIP site in the cervical esophagus and submucosal tumors with suspected multiple intramural metastases in the anal side of the thoracic esophagus. The patient underwent robot-assisted thoracoscopic esophagectomy with laryngopharyngectomy and cervical lymphadenectomy as radical salvage surgery 4 months after the last PDT procedure. After postoperative adjuvant chemotherapy using oral administration of tegafur/gimeracil/oteracil (oral 5-fluorouracil prodrug) for 1 year; at present, the patient is alive without recurrence 3 years after the operation.

Validation of dual atrioventricular nodal physiology in dual atrioventricular nodal non-reentrant tachycardia via adenosine triphosphate injection during atrial pacing: A novel insight into the role of leftward inferior extension.

INTRODUCTION: Dual atrioventricular nodal non-reentrant tachycardia (DAVNNT) is a rare and challenging-to-diagnose arrhythmia, without previous reports associating it with a leftward inferior extension (LIE). METHODS: Diagnosis was made using adenosine triphosphate (ATP) injection during atrial pacing in a suspected DAVNNT patient. RESULTS: Ablation of the rightward inferior extension was unsuccessful in eliminating DAVNNT; however, subsequent ablation of the LIE successfully eradicated the arrhythmia. CONCLUSION: This unique case, marked by the first instance of DAVNNT caused by LIE, diagnosed through ATP injection, underscores the utility of this diagnostic approach and broadens the spectrum of our understanding and management of this condition.

Symptomatic periesophageal vagal nerve injury by different energy sources during atrial fibrillation ablation.

Background: Symptomatic gastric hypomotility (SGH) is a rare but major complication of atrial fibrillation (AF) ablation, but data on this are scarce. Objective: We compared the clinical course of SGH occurring with different energy sources. Methods: This multicenter study retrospectively collected the characteristics and clinical outcomes of patients with SGH after AF ablation. Results: The data of 93 patients (67.0 ± 11.2 years, 68 men, 52 paroxysmal AF) with SGH after AF ablation were collected from 23 cardiovascular centers. Left atrial (LA) ablation sets included pulmonary vein isolation (PVI) alone, a PVI plus a roof-line, and an LA posterior wall isolation in 42 (45.2%), 11 (11.8%), and 40 (43.0%) patients, respectively. LA ablation was performed by radiofrequency ablation, cryoballoon ablation, or both in 38 (40.8%), 38 (40.8%), and 17 (18.3%) patients, respectively. SGH diagnoses were confirmed at 2 (1-4) days post-procedure, and 28 (30.1%) patients required re-hospitalizations. Fasting was required in 81 (92.0%) patients for 4 (2.5-5) days; the total hospitalization duration was 11 [7-19.8] days. After conservative treatment, symptoms disappeared in 22.3% of patients at 1 month, 48.9% at 2 months, 57.6% at 3 months, 84.6% at 6 months, and 89.7% at 12 months, however, one patient required surgery after radiofrequency ablation. Symptoms persisted for >1-year post-procedure in 7 patients. The outcomes were similar regardless of the energy source and LA lesion set. Conclusions: The clinical course of SGH was similar regardless of the energy source. The diagnosis was often delayed, and most recovered within 6 months, yet could persist for over 1 year in 10%.

Updated information regarding acute severe hepatitis of unknown origin in children: Viewpoints of and insights from pediatricians.

Recently, the morbidity of acute severe hepatitis of unknown origin in children (SHIC) has tended to decrease, but this condition should not be ignored because of its uncertain but severe nature. The current study briefly summarizes updated information regarding the epidemiological, clinical, and etiological aspects of SHIC based on the newest information available. Opinions from pediatricians are also presented. In light of the status quo of SHIC and COVID-19 globally, several suggestions are proposed to improve future studies, which could help to further explore the underlying mechanisms of SHIC in the context of COVID-19.

Insights from a patient with chronic lymphocytic leukemia complicating ALK+ anaplastic large cell lymphoma.

Chronic lymphocytic leukemia (CLL) that transforms into a more aggressive lymphoma has been termed Richter syndrome (RS). CLL with T-cell neoplasia is rarely reported; those with ALK+ anaplastic large cell lymphoma (ALCL) are also exceedingly rarely reported. A 63-year-old woman from the south of China presented with generalized lymphadenectasis and fever; she already had a prior diagnosis of CLL 9 years ago. As per her current diagnosis, it was CLL with ALK+ ALCL. The two-lymph node and bone marrow biopsies presented two types of cellular groups: i) left cervical lymph node biopsy suggested CLL (Ki67: 10%), along with bone marrow biopsy exhibited enhancement of the small lymphocytes (30%) with scant cytoplasm, round or irregular cell nuclei, and massive amounts of chromatin. Large cells (< 1%) that expressed CD30 and ALK were visible; The results of immunohistochemistry were as follows: CD20 (weak positive); PAX5 (positive); CD23 and CD5 (weak positive); and CD3, CD10, and CyclinD1 (negative); ii) left supraclavicular lymph node biopsy suggested ALK+ ALCL (Ki67: 70%). The final diagnosis was CLL with ALCL. The mechanisms of this condition are not fully understood, which might be associated with chronic stimulation of T cells by CLL cells along with immune dysfunction.

Erratum to "Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study".

[This corrects the article DOI: 10.1515/biol-2021-0105.].

Exploration of a Brain-Liver-Communication-Related Mechanism Involved in the Experimental Perimenopausal Depression Rat Model using Chaihu-Shugan-San.

Existing research suggests the involvement of a brain-liver-communication-related mechanism in the occurrence of depression. In this study, we selected Chaihu-Shugan-San (CSS), a traditional Chinese herbal medicine that can simultaneously affect liver and depression, as a probe to investigate the involvement of the brain-liver-communication-related mechanism in perimenopausal depression. A total of 50 experimental perimenopausal depression rat models were established by ovariectomy surgery (PMS) followed by chronic unpredictable mild stress (CUMS) processes. Animals underwent CSS treatment or treatments with CSS + Ly294002, an inhibitor of the PI3K/Akt signalling pathway. We observed the behavioural performances of depression and anxiety, serum concentrations of biochemical indices, serum estrogen two levels, hippocampal 5-HT and NE levels and the morphological changes in liver tissues. The protein and mRNA expressions of PI3K and Akt were also evaluated. CSS treatment significantly ameliorated the behavioural performance, partial biochemical indices and the morphological changes in the liver tissues of PMS + CUMS rats. Ly294002 partially inhibited the CSS effects. The expressions of PI3K and Akt were significantly downregulated by PMS + CUMS processes but upregulated by CSS treatment, which could be significantly suppressed by Ly294002. A brain-liver-communication-related mechanism may be involved in perimenopausal depression, where the PI3K/Akt signalling pathway plays a vital role.

Migration Capacity of Stem Cells from Human Exfoliated Deciduous Teeth Towards Glioma.

BACKGROUND: Stem cells from human exfoliated deciduous teeth (SHED) are a mesenchymal stem cell type and have recently attracted attention for their high proliferative rate, multipotency, and immunosuppressive properties. However, SHED have not yet been investigated for anticancer properties. We therefore investigated whether SHED can be used as a treatment modality, particularly for anti-glioma therapy. METHODS: In vitro, we examined the mobility of SHED and their ability to migrate towards glioma-conditioned medium and specific growth factors secreted by malignant gliomas. In vivo, we transplanted SHED into the left hemisphere of nude mice that had been previously implanted with human malignant glioma U87 cells into the right hemisphere. We assessed whether SHED had tumorigenic potential. RESULTS: SHED exhibited strong migration ability towards malignant glioma in both in vitro and in vivo assays. In vitro, SHED migrated towards glioma-conditioned medium and specific growth factors such as stem cell factor, platelet-derived growth factor BB, C-X-C motif chemokine ligand 12, and vascular endothelial growth factor. SHED were accumulated around tumor cells in the contralateral hemisphere 1 week after transplantation. Moreover, SHED remained in the brains of nude mice 150 days after transplantation. Finally, we verified that SHED had no malignant transformation or engraftment of SHED in the mouse brain. CONCLUSIONS: Our findings indicate that SHED can potentially be applied to track malignant glioma.

Increased anteroventral striatal dopamine transporter and motor recovery after subthalamic deep brain stimulation in Parkinson's disease.

OBJECTIVE: Subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease is effective; however, its mechanism is unclear. To investigate the degree of neuronal terminal survival after STN-DBS, the authors examined the striatal dopamine transporter levels before and after treatment in association with clinical improvement using PET with [11C]2ß-carbomethoxy-3ß-(4-fluorophenyl)tropane ([11C]CFT). METHODS: Ten patients with Parkinson's disease who had undergone bilateral STN-DBS were scanned twice with [11C]CFT PET just before and 1 year after surgery. Correlation analysis was conducted between [11C]CFT binding and off-period Unified Parkinson's Disease Rating Scale (UPDRS) scores assessed preoperatively and postoperatively. RESULTS: [11C]CFT uptake reduced significantly in the posterodorsal putamen contralateral to the parkinsonism-dominant side after 1 year; however, an increase was noted in the contralateral anteroventral putamen and ipsilateral ventral caudate postoperatively (p < 0.05). The percentage increase in [11C]CFT binding was inversely correlated with the preoperative binding level in the bilateral anteroventral putamen, ipsilateral ventral caudate, contralateral anterodorsal putamen, contralateral posteroventral putamen, and contralateral nucleus accumbens. The percentage reduction in UPDRS-II score was significantly correlated with the percentage increase in [11C]CFT binding in the ipsilateral anteroventral putamen (p < 0.05). The percentage reduction in UPDRS-III score was significantly correlated with the percentage increase in [11C]CFT binding in the ipsilateral anteroventral putamen, ventral caudate, and nucleus accumbens (p < 0.05). CONCLUSIONS: STN-DBS increases dopamine transporter levels in the anteroventral striatum, which is correlated with the motor recovery and possibly suggests the neuromodulatory effect of STN-DBS on dopaminergic terminals in Parkinson's disease patients. A preoperative level of anterior striatal dopamine transporter may predict reserve capacity of STN-DBS on motor recovery.

Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study.

In this pilot study, we compared the dynamic changes of circulating immune cells between patients with hepatocellular carcinoma (HCC) who underwent radiofrequency ablation (RFA) and hepatectomy. Seventy-three patients were enrolled in this study. Flow cytometry assay was performed to determine the immune cells in the peripheral blood mononuclear cells (PBMCs) before treatment and on days 7, 14, and 28 after treatment. We found that in the RFA group, the circulating cluster of differentiation (CD)4+ cells, the CD4+/CD8+ ratio, and natural killer (NK) cells continued to increase, and the circulating CD8+ cells continued to decrease after the treatment. In contrast, in the surgery group, the circulating CD4+ cells and CD4+/CD8+ ratio decreased over the first seven postoperative days and then began to increase, and CD8+ cells decreased on the first 7 postoperative days and began to increase thereafter. The changes of immune cells in tumor tissues consisted of an increase in the number of CD4+ cells, CD8+ cells, CD3+ cells, and NK cells immediately after RFA. Our results show that postoperative immune function continued to improve after RFA, but after surgery, it decreased in the first week and started to improve thereafter. These findings are important for clinicians when selecting the appropriate therapy for HCC.

[A Case of an Asymptomatic Coagulopathy after Peritoneovenous Shunt Placement for Malignant Ascites of Gastric Cancer].

The patient was a 61‒year‒old man who had an advanced gastric cancer with peritoneal dissemination. After chemotherapy, intraoperative findings during a total gastrectomy revealed the disappearance of the dissemination nodules. Although adjuvant chemotherapy was performed, the presence of massive ascites led to the recurrence of the peritoneal dissemination 5 months after the surgery. While the chemotherapy regimen was altered, we observed no reduction in malignant ascites. The patient complained of abdominal distention and was admitted to our hospital for symptom management. We performed a cell‒free and concentrated ascites reinfusion therapy(CART)several times. However, symptom management proved difficult; therefore, the patient underwent a peritoneovenous shunt(Denver shunt)placement. After the shunting, we observed no organ injury and improved abdominal distention; however, an asymptomatic coagulopathy was present in the course. Additionally, blood examinations showed increased FDP‒DD and thrombin‒antithrombin complex(TAT). However, 6 months after the shunting, coagulopathy improved and the patient reported the absence of abdominal distention. This report describes a patient with an asymptomatic coagulopathy after Denver shunt placement and evaluated the clinical course by using TAT values.

Comparison of the surgeries for the ossification of the posterior longitudinal ligament-related cervical spondylosis: A PRISMA-compliant network meta-analysis and literature review.

OBJECTIVE: We designed and performed a network meta-analysis to compare the clinical outcomes among the 5 surgeries-anterior cervical corpectomy and fusion (ACCF), anterior controllable antedisplacement fusion (ACAF), laminoplasty (LP), laminectomy (LC), and posterior decompression with instrumented fusion (PDF)-for patients with cervical spondylosis related to the ossification of the posterior longitudinal ligament (OPLL). METHODS: Databases, including PubMed, EMBASE, Cochrane Library, Google Scholar, and Web of Science (firstly available-2019) were selected for literature search. We performed a network meta-analysis with the included studies. A Newcastle-Ottawa scale was employed to assess the study quality of the included studies. RESULTS: Total 23 studies with 1516 patients were included in our analysis. We found that ACCF achieved the most improvement in the Japanese Orthopaedic Association Scores and excellent and good recovery rate, ACAF achieved the best improvement of the improvement rate and lordosis. LP got the best operative time and blood loss. CONCLUSIONS: Our results suggested that both anterior (ACCF and ACAF) and posterior (LP, LC, and PDF) procedures have their strengths and weaknesses. Clinicians need to select the most appropriate surgery with a comprehensive consideration of the clinical condition of each patient with OPLL-related cervical spondylosis.

In Vitro Investigation of the Cytotoxic Activity of Emodin 35 Derivative on Multiple Myeloma Cell Lines.

BACKGROUND: Bortezomib is used for treating multiple myeloma (MM); however, it has considerable adverse effects. Emodin has been reported to exhibit inhibitory effects on MM cell lines. We investigated the efficacy of emodin 35 (E35), an emodin derivative, using U266 and MM1s cell lines in treating MM and the efficacy of combining bortezomib and E35. METHODS: MTT assays were used to observe the effects of E35 on MM cell growth. The effects on cellular apoptosis were then observed using Annexin V/propidium iodide (PI) staining assay. The expression of apoptosis-related genes, including the caspase family, was examined. The efficacy of combining bortezomib and E35 was investigated by examining the expression of the Akt/mTOR/4EBP1 signaling pathway-related proteins. RESULTS: We report that E35 inhibited the growth of U266 and MM1s cells by inducing cellular apoptosis. Moreover, E35 downregulated the expression of apoptosis-related genes and suppressed the phosphorylation of Akt/mTOR/4EBP1 signaling pathway-related genes, thus exhibiting synergistic effects with bortezomib. All observed effects were dose-dependent. CONCLUSION: The results showed that E35 exhibited cytotoxic effects in MM cell lines in protein levels. Thus, E35, particularly in combination with bortezomib, may be considered as a promising treatment for MM; however, this requires further investigation in vivo.

Laparoscopic Enucleation of Hepatic Cysts Reduces the Recurrence of Nonparasitic Hepatic Cysts.

Background: Standard treatments for nonparasitic hepatic cysts (NPHCs) include laparoscopic deroofing (LD), percutaneous aspiration, and alcohol sclerotherapy. However, these treatments have limitations. LD and alcohol sclerotherapy, for example, fail to prevent NPHC recurrences, although alcohol sclerotherapy is satisfactorily effective in treating small cysts (diameter <5 cm), which do not usually need treatment. The present study introduces a novel surgical procedure, laparoscopic enucleation with intact cyst (LEIC), which may prevent postoperative cyst recurrence. Materials and Methods: In this study, we enrolled 14 patients, with NPHCs larger than 9 cm in diameter, who underwent LEIC. Dissection and coagulation were performed using the harmonic shear enucleation and bipolar coagulation techniques. We attempted to completely remove the cysts intact. Results: For all patients, symptoms disappeared after complete elimination of the cyst capsule. No complications (hemorrhage or bile leakage) were found during the perioperative period. The mean follow-up period was 19.3 months (range 10-38 months), during which no recurrences or complications were noted. Conclusions: LEIC is a novel surgical approach that shows satisfactory efficacy and safety in patients with large, surficial, and symptomatic NPHCs. LEIC's main advantage is that it can efficiently prevent cyst recurrence and decrease postoperative morbidity. However, its long-term efficacy and safety require further verification, especially with huge cysts.

Pharmacologic Treatment of Restless Legs Syndrome.

Restless legs syndrome (RLS)/Willis-Ekbom disease is a neurologic disorder characterized by a strong desire to move when at rest (usually in the evening) and paraesthesia in their lower legs. The most widely used therapies for first-line treatment of RLS are dopaminergic drugs; however, their long-term use can lead to augmentation. α2δ Ligands, opioids, iron, glutamatergic drugs, adenosine, and sleep aids have been investigated as alternatives. The pathogenesis of RLS is not well understood. Despite the efficacy of dopaminergic drugs in the treatment of this disorder, unlike in Parkinson's disease dopaminergic cell loss in the substantia nigra has not been observed in RLS. The etiology of RLS is likely complex, involving multiple neural pathways. RLS-related genes identified in genome-wide association studies can provide insight into the mechanistic basis and pathophysiology of RLS. Here we review the current treatments and knowledge of the mechanisms underlying RLS.

Development of a novel gripping test for the evaluation of the finger fine motor ability in MPTP-treated monkeys.

Assessing the finger fine motor ability is extremely important. However, conventional behavioral tests in monkeys are complicated and costly. We attempted to develop a new task to assess the precise finger grip in Parkinson's disease monkeys based on the principles of objectification, multipurpose, and simplification. This study involved seven adult male cynomolgus monkeys. A gripping test based on the previous food reaching test was developed. Parallel experiments of food reaching test and gripping test affected by the treatments of levodopa and deep brain stimulation of the subthalamic nucleus were performed to verify the utility of the gripping test. We found that gross motor ability (measured by food reaching test) could be significantly improved by both the subthalamic nucleus and levodopa administration, which reproduced the results of our previous study. The finger fine motor ability (measured by the gripping test) could be significantly improved by levodopa administration, but not by the subthalamic nucleus. Our results verified the utility and reliability of the gripping test, which is a simple, convenient, and objective task for evaluating the finger fine motor skill in Parkinson's disease monkeys. Mechanisms of the efficacy of deep brain stimulation on fine motor ability require further investigation.