Bosnian Journal of Basic Medical Sciences https://www.bjbms.org/ojs/index.php/bjbms <p>The BJBMS (Bosnian Journal of Basic Medical Sciences) is а premier venue for discoveries in basic and clinical biomedical science. The BJBMS was founded in 1998 and is published by the Association of Basic Medical Sciences, a nonprofit honor organization of physician-scientists.</p> <p>Broad readership and scope. The BJBMS reaches readers across a wide range of medical disciplines and sectors. The journal publishes basic and translational/clinical research submissions and reviews in all biomedical specialties, including Genetics and Molecular biology, Immunology, Microbiology, Pathology, Biochemistry, Pharmacology, Anatomy, Biomaterials, new and emerging research and diagnostic methods, new and emerging medical entities, and others.</p> Association of Basic Medical Sciences of FBIH en-US Bosnian Journal of Basic Medical Sciences 1512-8601 Uvulopalatopharyngoplasty and barbed reposition pharyngoplasty with and without hyoid suspension for obstructive sleep apnea hypopnea syndrome: A comparison of long-term functional results https://www.bjbms.org/ojs/index.php/bjbms/article/view/4724 <p>Obstructive sleep apnea hypopnea syndrome (OSAHS) is a common condition; when conservative approaches are not effective, surgical techniques aimed at reducing the airway obstruction effect are used. This retrospective study aimed at comparing the functional outcomes in patients with OSAHS undergoing uvulopalatopharyngoplasty (UPPP) according to Fairbanks and barbed reposition pharyngoplasty (BRP) according to Mantovani, with or without hyoid suspension (HS). One-hundred twenty-two consecutive OSAHS patients who underwent surgical treatment were included in the study. Patients were divided into 4 groups; all patients underwent preoperative and postoperative polysomnography (PSG) with apnea/hypopnea index (AHI) and oxygen desaturation index (ODI) evaluation, and Epworth Sleepiness Scale (ESS) evaluation. The results were analyzed according to the different surgical procedures in relation to the preoperative PSG and anthropometric data. A significant reduction was observed at 18-month follow-up for patients in BRP group for body mass index (<em>p</em> = 0.004), ESS (<em>p</em> &lt; 0.0001), ODI (<em>p</em> &lt; 0.0001), and AHI (<em>p</em> &lt; 0.0001). Risk factors for poor postoperative AHI reduction were evaluated; preoperative AHI was the strongest independent protective factor, while preoperative ODI was the strongest risk factor. The association of HS with UPPP or BRP showed significant results in terms of higher postoperative AHI reduction only when associated to UPPP (<em>p</em> &lt; 0.0001). This study showed that the BRP technique was more effective compared to UPPP for patients with OSAHS. The association of HS showed greater benefits in UPPP compared to BRP. Randomized prospective trials with longer follow-up are necessary to confirm our results and formulate a more accurate indication of the optimal therapeutic strategy.</p> Antonio Minni Fabrizio Cialente Massimo Ralli Andrea Colizza Quirino Lai Angelo Placentino Melania Franco Valeria Rossetti Marco de Vincentiis Copyright (c) 2020 Antonio Minni, Fabrizio Cialente, Massimo Ralli, Andrea Colizza, Quirino Lai, Angelo Placentino, Melania Franco, Valeria Rossetti, Marco de Vincentiis https://creativecommons.org/licenses/by/4.0 2021-06-01 2021-06-01 21 3 364 369 10.17305/bjbms.2020.4724 A three-dimensional computed tomography study to determine the ideal method for fluoroscopically-guided bone marrow aspiration from the iliac crest https://www.bjbms.org/ojs/index.php/bjbms/article/view/4744 <p>Bone marrow aspiration (BMA) through the iliac crest is potentially unsafe due to the vicinity of neurovascular structures in the greater sciatic notch. Our objective was to investigate the safety of a recently described BMA technique, specifically a trajectory from the posterior superior iliac spine (PSIS) to the anterior inferior iliac spine (AIIS). We conducted a chart review of 260 patients, analyzing three-dimensional reconstructed computed tomography images of the pelvis and sacrum to validate that this new approach offers a wide safety margin from the greater sciatic notch. Analysis of three-dimensional computed tomography scans demonstrated that the PSIS to AIIS trajectory never crossed the greater sciatic notch. The trajectory was noted to be at least one cm away from the greater sciatic notch in all measurements. The new trajectory entered the PSIS at 25.29 ± 4.34° (left side) and 24.93 ± 4.15° (right side) cephalad from the transverse plane, and 24.58 ± 4.99° (left side) and 24.56 ± 4.67° (right side) lateral from the mid-sagittal plane. The area of bone marrow encountered with the new approach was approximately 22.5 cm<sup>2</sup>. Utilizing the same CT scans, the trajectory from the traditional approach crossed the greater sciatic notch in all scans, highlighting the potential for violating the greater sciatic notch boundary and damaging important neurovascular structures. Statistically significant sex-related differences were identified in needle trajectory angles for both approaches. We conclude that based on this three-dimensional computed tomography study, a trajectory from the PSIS to the AIIS for BMA may offer a wide safety margin from the greater sciatic notch.</p> Ryan S. D'Souza Langping Li Shuai Leng Christine Hunt Luke Law Casey Muir Jason Eldrige Mohamad Bydon Meng Chi Shane Shapiro William D. Mauck Wenchun Qu Copyright (c) 2020 Ryan S. D'Souza, Langping Li, Shuai Leng, Christine Hunt, Luke Law, Casey Muir, Jason Eldrige, Mohamad Bydon, Meng Chi, Shane Shapiro, William D. Mauck, Wenchun Qu https://creativecommons.org/licenses/by/4.0 2021-06-01 2021-06-01 21 3 370 377 10.17305/bjbms.2020.4744 Clinical management of chronic mercury intoxication secondary to skin lightening products: A proposed algorithm https://www.bjbms.org/ojs/index.php/bjbms/article/view/4759 <p>Mercury is a toxic substance that is commonly used in skin lightening products. Various effects on humans have been observed, which affect both users and non-users. Many studies reported delayed diagnosis and treatment, even after weeks of hospitalization. The possible reasons are non-specific clinical manifestation and lack of awareness and knowledge regarding chronic mercury intoxication secondary to skin lightening products. A thorough history of mercury exposure is crucial. Physical assessment and relevant supporting tests are indicated to establish a diagnosis. Blood and urine mercury levels are an essential examination for diagnosis and monitoring of the progress and response to treatment. The primary treatment is the discontinuation of the skin lightening products. Chelation therapy is not mandatory and is usually indicated for symptomatic patients. The prognosis depends on the duration of the product use, concentration of mercury in the skin product, and the severity of clinical presentation.</p> Fitri Fareez Ramli Copyright (c) 2020 Fitri Fareez Ramli https://creativecommons.org/licenses/by/4.0 2021-06-01 2021-06-01 21 3 261 269 10.17305/bjbms.2020.4759 Lingual cyst with respiratory epithelium: The importance of differential diagnosis https://www.bjbms.org/ojs/index.php/bjbms/article/view/4716 <p>The lingual cyst with respiratory epithelium (LCRE) is a very rare congenital cyst of the tongue, floor of the mouth, pharynx, or hypopharynx with 21 cases reported in the literature [1,2]. Differential diagnosis is very important for patients presenting with lingual cysts, as this may impact treatment and follow-up. The LCRE should be included in the different diagnosis of a dermoid cyst [3], teratoid cyst [4], epidermoid cyst [5], thyroglossal duct cyst [6], lymphoepithelial cyst [7], and mucocele or ranula [8]. Each entity has a peculiar histologic presentation, although the clinical aspect may be very similar [1]. The dermoid cyst is lined by a keratinized squamous epithelium and contains skin appendages in the cyst. The epidermoid cyst is similar to the dermoid cyst but is characterized by non-keratinized squamous epithelium and has a lumen filled with keratin. The teratoid cyst contains derivatives of the endoderm, ectoderm, and/or mesoderm. The thyroglossal duct cyst is usually lined by columnar, stratified squamous epithelium, or an intermediate transition type of epithelium, with the mandatory presence of thyroid tissue in the cyst wall. The lymphoepithelial cyst is identified by the presence of lymphoid aggregates in the cyst wall. A mucous retention cyst, so-called mucocele or ranula, contains mucin and granulation tissue [1].</p> <p>Read the full text <a href="https://bjbms.org/ojs/index.php/bjbms/article/view/4716/1339"><strong>[PDF]</strong></a></p> Fabrizio Cialente Giulia De Soccio Vincenzo Savastano Michele Grasso Michele Dello Spedale Venti Massimo Ralli Mara Riminucci Marco de Vincentiis Alessandro Corsi Antonio Minni Copyright (c) 2020 Fabrizio Cialente, Giulia De Soccio, Vincenzo Savastano, Michele Grasso, Michele Dello Spedale Venti, Massimo Ralli, Mara Riminucci, Marco de Vincentiis, Alessandro Corsi, Antonio Minni https://creativecommons.org/licenses/by/4.0 2021-06-01 2021-06-01 21 3 378 382 10.17305/bjbms.2020.4716 Surgical anatomy of microsurgical 3-level anterior cervical discectomy and fusion C4–C7 https://www.bjbms.org/ojs/index.php/bjbms/article/view/4895 <p>Anterior cervical discectomy and fusion (ACDF) is one of the most common spinal procedures, frequently used for the treatment of cervical spine degenerative diseases. It was first described in 1958. Interestingly, to our knowledge, 3-level ACDF has not been previously published as a peer-reviewed video case with a detailed description of intraoperative microsurgical anatomy. In this video, we present the case of a 33-year-old male who presented with a combination of myelopathy (hyperreflexia and long tract signs in the upper and lower extremities) and bilateral radiculopathy of the upper extremities. He had been previously treated conservatively with physical therapy and pain management for 6 months without success. We performed 3-level microsurgical ACDF from C4 to C7. All 3 levels were decompressed, and bone allografts were placed to achieve intervertebral body fusion. A titanium plate was utilized from C4 to C7 for internal fixation. The patient was discharged home on the first postoperative day. His pain, numbness and tingling resolved, as well as his myelopathy. No perioperative complications were encountered. Herein we present the surgical anatomy of our operative technique including certain technical tips. Written consent was obtained directly from the patient.<br><br>VIDEO ANNOTATIONS<br>01:13 — opening the surgery site<br>02:29 — positioning of retractors<br>03:02 — start of 3-level discectomy<br>06:04 — allograft placement and fixation<br>08:20 — drain placement and closure</p> Domagoj Gajski Alicia R. Dennis Kenan I. Arnautovic Copyright (c) 2020 Domagoj Gajski, Alicia R. Dennis, Kenan I. Arnautovic https://creativecommons.org/licenses/by/4.0 2021-06-01 2021-06-01 21 3 258 260 10.17305/bjbms.2020.4895 ANKRD22 enhances breast cancer cell malignancy by activating the Wnt/β-catenin pathway via modulating NuSAP1 expression https://www.bjbms.org/ojs/index.php/bjbms/article/view/4701 <p>Breast cancer is one of the most prevalent malignancies in women worldwide. Although great advancements have been achieved in the diagnosis and treatment of breast cancer, the prognosis of patients with breast cancer is still poor due to distal recurrence and metastasis after surgery. This study aimed to assess the role of ankyrin repeat domain 22 (ANKRD22) in the progression of breast cancer and investigate the molecular mechanism. Using immunohistochemistry, we demonstrated that the expression level of ANKRD22 in human breast cancer tissues was significantly higher than that in normal breast tissues. <em>ANKRD22</em> knockdown inhibited the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of breast cancer cells, as confirmed by BrdU, colony formation, transwell, and immunoblot assays. Immunoblot assays further indicated that ANKRD22 regulated the expression of nucleolar and spindle-associated protein 1 (NuSAP1) and then caused the activation of Wnt/β-catenin signaling pathway. Moreover, overexpression of <em>NUSAP1</em> reversed the inhibitory effects of <em>ANKRD22</em> knockdown on the proliferation, invasion, and EMT of breast cancer cells. In summary, this study demonstrated that ANKRD22 enhanced breast cancer cell malignancy by activating the Wnt/β-catenin pathway via modulating NuSAP1 expression, which might shed light on new therapeutic approaches for breast cancer.</p> Yange Wu Hongxia Liu Yufeng Gong Bo Zhang Wenxiu Chen Copyright (c) 2020 Yange Wu, Hongxia Liu, Yufeng Gong, Bo Zhang, Wenxiu Chen https://creativecommons.org/licenses/by/4.0 2021-06-01 2021-06-01 21 3 294 304 10.17305/bjbms.2020.4701 LAPTM4B promotes the progression of nasopharyngeal cancer https://www.bjbms.org/ojs/index.php/bjbms/article/view/4738 <p>Lysosomal protein transmembrane 4 beta (LAPTM4B) is a protein that contains four transmembrane domains. The impact of LAPTM4B on the malignancy of nasopharyngeal carcinoma (NPC) remains unclear. In the present study, we aimed to investigate the role of LAPTM4B in NPC. NPC tissue samples were used to evaluate the expression of LAPTM4B and its relationship with patient prognosis. Furthermore, we inhibited the expression of LAPTM4B in NPC cell lines and examined the effects of LAPTM4B on NPC cell proliferation, migration, and invasion. We found that LAPTM4B protein was mainly localized in the cytoplasm and intracellular membranes of NPC cells. LAPTM4B protein was upregulated in NPC tissues and cell lines. High LAPTM4B expression was closely related to pathological subtypes and disease stages in NPC patients. NPC patients with high LAPTM4B expression had a worse prognosis. <em>LAPTM4B</em> knockdown inhibited the proliferation, migration, and invasion ability of NPC cells. LAPTM4B plays a cancer-promoting role in the progression of NPC and may be a potential target for NPC therapy.</p> Qun Su Hongtao Luo Ming Zhang Liying Gao Fengju Zhao Copyright (c) 2020 Qun Su, Hongtao Luo, Ming Zhang, Liying Gao, Fengju Zhao https://creativecommons.org/licenses/by/4.0 2021-06-01 2021-06-01 21 3 305 312 10.17305/bjbms.2020.4738 The effect and molecular mechanism of hypoxia on proliferation and apoptosis of CD133+ renal stem cells https://www.bjbms.org/ojs/index.php/bjbms/article/view/4887 <p>Congenital hydronephrosis caused by ureteropelvic junction obstruction (UPJO) eventually leads to renal interstitial fibrosis and atrophy, after a series of pathophysiological problems. Renal repair after injury depends on renal stem cells. This study aimed to determine the expression of renal stem cell marker CD133 in children of different ages and the regulatory effect of stem cell microenvironment. Renal stem cells from children of different ages were identified and screened out by flow cytometry in the study. Children with hydronephrosis were divided into neonates, infants, preschool age, school age, and adolescents groups. A hypoxic cell model prepared with CoCl<sub>2</sub> was developed to detect the effect of hypoxia on the proliferation and apoptosis of renal stem cells. The effect and molecular mechanism of hypoxia-inducible factor 1-alpha (HIF-1α) on the proliferation and apoptosis of renal stem cells were also explored. Both hypoxia and HIF-1α significantly promoted the proliferation of renal stem cells and inhibited cell apoptosis. HIF-1α could bind to the promoter region of proliferating cell nuclear antigen (<em>PCNA</em>) and <em>PROM1 </em>(CD133) to mediate their transcription and expression. The content of CD133<sup>+</sup> renal stem cells was the highest in the neonatal group and it decreased with the increase of age. Taken together, this study clarified the effect of age on the content of human renal stem cells and determined the regulatory mechanism of hypoxia on renal stem cells. We expect our results to provide a research basis for the treatment and clinical application of renal stem cells.</p> Hong Liu Cui Liu Yan Qu Copyright (c) 2020 Hong Liu, Cui Liu, Yan Qu https://creativecommons.org/licenses/by/4.0 2021-06-01 2021-06-01 21 3 313 322 10.17305/bjbms.2020.4887 Safety and effectiveness of new embolization microspheres SCBRM for intermediate-stage hepatocellular carcinoma: A feasibility study https://www.bjbms.org/ojs/index.php/bjbms/article/view/4770 <p>Transarterial chemoembolization (TACE) is, currently, the recommended treatment for hepatocellular carcinoma (HCC). However, long-term chemoembolization triggers the inflammatory response and may lead to postembolization syndrome (PES). Although several types of degradable microspheres have been developed to reduce drug toxicity and PES incidence, the clinical outcomes remain unsatisfactory. Previously, we have developed a new type of spherical, calibrated, biodegradable, radiopaque microspheres (SCBRM) and demonstrated their safety and efficacy in a pig model. Thus, the goal of this feasibility study was to determine the clinical safety and efficacy of the new SCBRM in intermediate-stage HCC patients. In this study, 12 intermediate-stage HCC patients underwent TACE using SCBRM with a calibrated size of 100–250 μm. The disease control rates at 1 month and 3 months after TACE-SCBRM treatment were 100% and 75.0%, respectively. The objective response rates at 1 month and 3 months after treatment were 66.7% and 58.3%, respectively. Very few adverse events were observed with one patient developing nausea. One day after the treatment, alanine aminotransferase, alanine aminotransferase, and total bilirubin levels were slightly elevated in the patients, but all returned to baseline on day 7. The median and mean overall survival times were 33 months (interquartile range, 12.8–42.0) and 29.2 ± 14.3 months, respectively. The 1-year and 2-year survival rates were 91.7% and 58.3%, respectively. In conclusion, TACE with the new SCBRM microspheres is clinically safe and effective, and it represents a promising approach in the management of intermediate-stage HCC.</p> Yi-Sheng Liu Xi-Zhang Lin Chiung-Yu Chen Yen-Cheng Chiu Jui-Wen Kang Hung-Wen Tsai Hui-Yu Hung Chi-Ming Ho Ming-Ching Ou Copyright (c) 2020 Yi-Sheng Liu, Xi-Zhang Lin, Chiung-Yu Chen, Yen-Cheng Chiu, Jui-Wen Kang, Hung-Wen Tsai, Hui-Yu Hung, Chi-Ming Ho, Ming-Ching Ou https://creativecommons.org/licenses/by/4.0 2021-06-01 2021-06-01 21 3 339 345 10.17305/bjbms.2020.4770 Postoperative respiratory depression after hysterectomy https://www.bjbms.org/ojs/index.php/bjbms/article/view/5026 <p>To investigate if sex-specific physiologic characteristics could impact postoperative respiratory depression risks in women, we studied incidence and risk factors associated with postoperative respiratory depression in a gynecologic surgical cohort. Only hysterectomies performed under general anesthesia from 2012 to 2017 were included to minimize interprocedural variability. Respiratory depression was defined as episodes of apnea, hypopnea, hypoxemia, pain-sedation mismatch, unplanned positive airway pressure device application, or naloxone administration in the post-anesthesia care unit. Multivariable logistic regression was used to explore the association with clinical characteristics. From 1,974 hysterectomies, 253 had postoperative respiratory depression, yielding an incidence of 128 (95% confidence interval, 114–144) per 1,000 surgeries. Risk factors associated with respiratory depression were older age (odds ratio 1.22 [95% confidence interval 1.02–1.46] per decade increase, <em>p </em>= 0.03), lower body weight (0.77 [0.62–0.94] per 10 kg/m<sup>2</sup>, <em>p</em> = 0.01), and higher intraoperative opioid dose (1.05 [1.01–1.09] per 10 mg oral morphine equivalents, <em>p</em> = 0.01); while sugammadex use was associated with a reduced risk (0.48 [0.30–0.75], <em>p</em> = 0.002). Respiratory depression was not associated with increased hospital stay, postoperative complications, or mortality. Postoperative respiratory depression risk in women increased with age, lower weight, and higher intraoperative opioids and decreased with sugammadex use; however, it was not associated with postoperative pulmonary complications.</p> Mariana L. Laporta Michelle O. Kinney Darrell R. Schroeder Juraj Sprung Toby N. Weingarten Copyright (c) 2020 Mariana L. Laporta, Michelle O. Kinney, Darrell R. Schroeder, Juraj Sprung, Toby N. Weingarten https://creativecommons.org/licenses/by/4.0 2021-06-01 2021-06-01 21 3 346 351 10.17305/bjbms.2020.5026 Dysbiosis of gut microbiota in inflammatory bowel disease: Current therapies and potential for microbiota-modulating therapeutic approaches https://www.bjbms.org/ojs/index.php/bjbms/article/view/5016 <p>There is a growing body of evidence reinforcing the unique connections between the host microbiome, health, and diseases. Due to the extreme importance of the symbiotic relationship between the intestinal microbiome and the host, it is not surprising that any alteration in the gut microbiota would result in various diseases, including inflammatory bowel disease (IBD), Crohn’s disease, (CD) and ulcerative colitis (UC). IBD is a chronic, relapsing-remitting condition that is associated with significant morbidity, mortality, compromised quality of life, and costly medical care. Dysbiosis is believed to exacerbate the progression of IBD. One of the currently used treatments for IBD are anti-tumor necrosis factor (TNF) drugs, representing a biologic therapy that is reported to have an impact on the gut microbiota composition. The efficacy of anti-TNF agents is hindered by the possibility of non-response, which occurs in 10-20% of treated patients, and secondary loss of response, which occurs in up to 30% of treated patients. This underscores the need for novel therapies and studies that evaluate the role of the gut microbiota in these conditions. The success of any therapeutic strategy for IBD depends on our understanding of the interactions that occur between the gut microbiota and the host. In this review, the health and disease IBD-associated microbiota patterns will be discussed, in addition to the effect of currently used therapies for IBD on the gut microbiota composition, as well as new therapeutic approaches that can be used to overcome the current treatment constraints.</p> Dikhnah Alshehri Omar Saadah Mahmoud Mosli Sherif Edris Rashad Alhindi Ahmed Bahieldin Copyright (c) 2020 Dikhnah Alshehri, Omar Saadah, Mahmoud Mosli, Sherif Edris, Rashad Alhindi, Ahmed Bahieldin https://creativecommons.org/licenses/by/4.0 2021-06-01 2021-06-01 21 3 270 283 10.17305/bjbms.2020.5016 Development and validation of prognostic nomogram for lung cancer patients below the age of 45 years https://www.bjbms.org/ojs/index.php/bjbms/article/view/5079 <p>This study aimed to establish a nomogram for the prognostic prediction of patients with early-onset lung cancer (EOLC) in both overall survival (OS) and cancer-specific survival (CSS). EOLC patients diagnosed between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and further divided into training and validation sets randomly. The prognostic nomogram for predicting 3-, 5- and 10-years OS and CSS was established based on the relative clinical variables determined by the multivariate Cox analysis results. Furthermore, the predictive performance of nomogram was assessed by concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis (DCA) curve. A total of 1,822 EOLC patients were selected and randomized into a training cohort (1,275, 70%) and a validation cohort (547, 30%). The nomograms were established based on the statistical results of Cox analysis. In training set, the C-indexes for OS and CSS prediction were 0.797 (95% confidence interval [CI]: 0.773-0.818) and 0.794 (95%CI:0.771-0.816). Significant agreement in the calibration curves was noticed in the nomogram models. The results of ROC and DCA indicated nomograms possessed better predict performance compared with TNM-stage and SEER-stage. And the area under the curve (AUC) of the nomogram for OS and CSS prediction in ROC analysis were 0.766 (95%CI:0.745-0.787) and 0.782 (95%CI:0.760-0.804) respectively. The prognostic nomogram provided an accurate prediction of 3-, 5-, and 10-year OS and CSS of EOLC patients which contributed clinicians to optimize individualized treatment plans.&nbsp;</p> Lili Dai Wei Wang Qi Liu Tongjia Xia Qikui Wang Qingqing Chen Ning Zhu Yu Cheng Ying Yan Jun Shu Kaixin Qu Copyright (c) 2020 Kaixin Qu, Lili Dai, Wei Wang, Qi Liu, Tongjia Xia, Qikui Wang, Qingqing Chen, Ning Zhu, Yu Cheng, Ying Yan, Jun Shu https://creativecommons.org/licenses/by/4.0 2021-06-01 2021-06-01 21 3 352 363 10.17305/bjbms.2020.5079 Alectinib and lorlatinib function by modulating EMT-related proteins and MMPs in NSCLC metastasis https://www.bjbms.org/ojs/index.php/bjbms/article/view/5066 <p>Most advanced non-small cell lung cancer (NSCLC) patients are accompanied by brain metastasis which is the major cause of increased mortality. The fusion rearrangement of anaplastic lymphoma kinase (ALK) gene is an important feature of brain metastasis in lung cancer. The novel ALK inhibitors alectinib and lorlatinib are shown to be effective against NSCLC brain metastasis, while their underlying mechanism of action is unclear. Epithelial–mesenchymal transition (EMT) proteins and matrix metalloproteinases (MMPs) play important roles in brain metastasis by regulating the blood-brain barrier (BBB). To reveal the molecular function of alectinib and lorlatinib, we explored their effects on the cellular levels of EMT markers: VIM and FN1 and the matrix metalloproteinases MMP-9 and MMP-7. The mRNA and protein levels of VIM, FN1, MMP-9, and MMP-7 were elevated in H3122 cells. However, upon alectinib and lorlatinib treatment, the levels were significantly reduced. Similar results were obtained when these experiments were performed either in a dose-dependent or time-dependent manner. Furthermore, alectinib and lorlatinib also inhibited the cell viability and migration of H3122 cells. Interestingly, in comparison to individual drugs, the combination of alectinib and lorlatinib was found to be substantially more effective. Overall, these results suggest that alectinib and lorlatinib possibly function through the downregulation of MMPs and EMT in NSCLC metastasis.</p> Xu Feng En-Shi Xu Copyright (c) 2020 Xu Feng, En-Shi Xu https://creativecommons.org/licenses/by/4.0 2021-06-01 2021-06-01 21 3 331 338 10.17305/bjbms.2020.5066 Raloxifene inhibits the overexpression of TGF-β1 in cartilage and regulates the metabolism of subchondral bone in rats with osteoporotic osteoarthritis https://www.bjbms.org/ojs/index.php/bjbms/article/view/5142 <p>Overexpression of transforming growth factor-beta 1 (TGF-β1) and subchondral bone remodelling play key roles in osteoarthritis (OA). Raloxifene (RAL) reduces the serum level of TGF-β1 in postmenopausal women. However, the effect of RAL on TGF-β1 expression in articular cartilage is still unclear. Therefore, we aimed to investigate the protective effect of RAL on osteoporotic osteoarthritis via affecting TGF-β1 expression in cartilage and the metabolism of subchondral bone. Osteoporotic osteoarthritis was induced by a combination of anterior cruciate transection (ACLT) and ovariectomy (OVX). Rats were divided into five groups (n = 12): The sham group, the ACLT group, the OVX group, the ACLT + OVX group, and the RAL group (ACLT + OVX + RAL, 6.25 mg/kg/day for 12 weeks). Assessment was performed by histomorphology, microcomputed tomography (micro-CT) scan, immunohistochemistry, and tartrate-resistant acid phosphatase (TRAP) staining. We found that severe cartilage degeneration was shown in the ACLT + OVX group. The histomorphological scores, the levels of TGF-β1, and its related catabolic enzymes and osteoclasts numbers in the ACLT + OVX group were higher than those in other groups (<em>p </em>&lt; 0.05). Furthermore, structure model index (SMI) and trabecular spacing (Tb.Sp) were decreased (<em>p </em>&lt; 0.05), while bone mineral density (BMD), bone volume fraction (BV/TV), and trabecular number (Tb.N) were increased by RAL compared with the ACLT + OVX group (<em>p </em>&lt; 0.05). Our findings demonstrated that RAL in clinical doses retards the development of osteoporotic osteoarthritis by inhibiting the overexpression of TGF-β1 in cartilage and regulating the metabolism of subchondral bone. These results provide support for RAL in the expansion of clinical indication for prevention and treatment in postmenopausal osteoarthritis.</p> Shao-Hua Ping Fa-Ming Tian Hao Liu Qi Sun Li-Tao Shao Qiang-Qiang Lian Liu Zhang Copyright (c) 2020 Shao-Hua Ping, Fa-Ming Tian, Hao Liu , Qi Sun, Li-Tao Shao, Qiang-Qiang Lian, Liu Zhang https://creativecommons.org/licenses/by/4.0 2021-06-01 2021-06-01 21 3 284 293 10.17305/bjbms.2020.5142 Multidimensional study of CDCA family members in gastric carcinoma with prognostic value https://www.bjbms.org/ojs/index.php/bjbms/article/view/5783 <p>Gastric cancer (GC) represents a widespread malignancy, having a poor prognosis, making it necessary to search for reliable biomarkers. Cell Division Cycle Associated protein (CDCA) family, comprising CDCA1-8, acts as a key in tumor progression. However, CDCAs expression and their impact on prognosis in gastric cancer, especially stomach adenocarcinoma (STAD), have not been clarified. Consequently, we carried out a multifaceted study aimed at exploring the CDCAs expression levels and appraising their potential prognostic values in patients with STAD, using bioinformatic tools. Remarkable upregulation of all 8 CDCAs was identified in STAD tissues, as compared with the healthy tissues. Elevated CDCA4/7/8 mRNA expression predicted a short overall survival (OS), while STAD patients, showing increased transcriptional levels of CDCA7, exhibited a short disease-free survival (DFS). The most frequent alteration was low mRNA expression among all mutations. The function enrichment analysis incorporating Gene Ontology (GO) together with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that cell cycle, foxO signaling pathway and Epstein-Barr virus were relevant to the main functions of CDCAs. Finally, through the immune infiltration analysis, a remarkable relationship was found between CDCAs expression and the extent of infiltrating levels in six immunocytes. Therefore, differentially expressed CDCAs were assessed as potential biomarkers of the prognosis of STAD patients, aiming at the improved survival of these patients. Furthermore, this study might offer new ideas for the design and development of immunotherapeutic drugs.</p> Peixin Lu Wen Cheng Kexin Fang Bin Yu Copyright (c) 2021 Peixin Lu, Wen Cheng, Kexin Fang, Bin Yu https://creativecommons.org/licenses/by/4.0 2021-05-12 2021-05-12 21 3 10.17305/bjbms.2021.5783 Reply to the letter regarding “Chronic mechanical irritation and oral squamous cell carcinoma: A systematic review and meta-analysis” https://www.bjbms.org/ojs/index.php/bjbms/article/view/6006 <p>Dear Editor,</p> <p>We thank Dr. Jian Xie for the valuable inputs on our paper titled ‘Chronic mechanical irritation and oral squamous cell carcinoma: A systematic review and meta-analysis [1].’ The first concern of Dr. Xie was that we had included two studies that were based on the same population. We re-examined these papers, one was published in 2010 [2] and the other in 2017 [3] by the same group of authors. Given the significant time difference between the two papers, we did not want to presume they were from the same sample population. There is no clear evidence that they are from the same sample population.</p> <p>Read more in <a href="https://www.bjbms.org/ojs/index.php/bjbms/article/view/6006/2188">PDF</a>.</p> Archana A Gupta Supriya Kheur Saranya Varadarajan Sameena Parveen Harisha Dewan Yaser Ali Alhazmi A. Thirumal Raj Luca Testarelli Shankargouda Patil Copyright (c) 2021 Archana A Gupta, Supriya Kheur, Saranya Varadarajan, Sameena Parveen, Harisha Dewan, Yaser Ali Alhazmi, A. Thirumal Raj, Luca Testarelli, Shankargouda Patil https://creativecommons.org/licenses/by/4.0 2021-05-09 2021-05-09 21 3 10.17305/bjbms.2021.6006 Letter regarding “Chronic mechanical irritation and oral squamous cell carcinoma: A systematic review and meta-analysis” https://www.bjbms.org/ojs/index.php/bjbms/article/view/5939 <p>Dear Editor:</p> <p>We have read with a great interest the article by Gupta et al. [1] who performed a meta-analysis exploring the association between chronic mechanical irritation and oral squamous cell carcinoma. The conclusion of the meta-analysis is that chronic oral mucosa irritation has a significant association with oral squamous cell carcinoma, and the nature of association could be that of a potential co-factor (dependent risk factor) rather than an independent risk factor.</p> <p>Read more in <a href="https://www.bjbms.org/ojs/index.php/bjbms/article/view/5939/2187">PDF.</a></p> Jian Xie Lang Li Copyright (c) 2021 Jian Xie, Lang Li https://creativecommons.org/licenses/by/4.0 2021-05-09 2021-05-09 21 3 10.17305/bjbms.2021.5939 LncRNA SENCR suppresses abdominal aortic aneurysm formation by inhibiting smooth muscle cells apoptosis and extracellular matrix degradation https://www.bjbms.org/ojs/index.php/bjbms/article/view/4994 <p>Abdominal aortic aneurysm (AAA) is a progressive chronic dilatation of the abdominal aorta without effective medical treatment. This study aims to clarify the potential of long non-coding RNA SENCR as a treatment target in AAA. Angiotensin II (Ang-II) was used to establish AAA model <em>in vitro</em> and <em>in vivo</em>. Reverse transcription quantitative PCR and western blot were performed to measure the expression of SENCR and proteins, respectively. Annexin V-FITC/PI double staining was carried out to detect the apoptotic rate in vascular smooth muscle cells (VSMCs), and cell apoptosis in aortic tissues was determined by TUNEL staining. Besides, hematoxylin and eosin and Elastica van Gieson staining were performed for histological analysis of aortic tissues. SENCR was downregulated in AAA tissues and Ang-II-stimulated VSMCs. Overexpression of SENCR could inhibit Ang-II-induced VSMC apoptosis, while inhibition of SENCR facilitated Ang-II-induced VSMC apoptosis. Moreover, the expression of matrix metalloproteinase (MMP)-2 and MMP-9 in Ang-II-induced VSMCs was reduced following SENCR overexpression, while tissue inhibitor of metalloproteinases 1 (TIMP-1) expression was increased. <em>In vivo</em>, overexpression of SENCR improved the pathological change in aortic tissues and the damage in arterial wall elastic fibers induced by Ang-II, as well as suppressed Ang-II-induced cell apoptosis and extracellular matrix degradation. Overall, SENCR was decreased in AAA. Overexpression of SENCR inhibited AAA formation via inhibition of VSMC apoptosis and extracellular matrix degradation. We provided a reliable evidence for SENCR acting as a potential target for AAA treatment.</p> Zhou Cai Jianhua Huang Junxiao Yang Baihong Pan Wei Wang Yangyang Ou Xianwei Wang Pu Yang Copyright (c) 2020 Zhou Cai, Jianhua Huang, Junxiao Yang, Baihong Pan, Wei Wang, Yangyang Ou, Xianwei Wang, Pu Yang https://creativecommons.org/licenses/by/4.0 2021-04-30 2021-04-30 21 3 323 330 10.17305/bjbms.2020.4994 Pharmacogenetics of new classes of antidiabetic drugs https://www.bjbms.org/ojs/index.php/bjbms/article/view/5646 <p>Type 2 diabetes (T2D) has a continuously rising prevalence worldwide. Pharmacogenetics has been recognized as a promising concept for pharmacological treatment of T2D, as antidiabetic drugs are not equally effective and safe for all patients, and the costs of diabetes treatment are increasing. The latest published guidelines on T2D treatment firmly endorse the use of newer antidiabetic drugs, sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-IVi), and glucagon-like peptide-1 receptor agonists (GLP-1RA), considering their satisfactory pharmacological effect and good safety profile. Furthermore, SGLT2i and GLP-1RA show protective effects in patients with established atherosclerotic cardiovascular disease and chronic kidney disease. However, there has been growing evidence that the effectiveness and safety of these drug classes could depend on genetic variability. Here, we summarized the results of the published studies on the pharmacogenetic biomarkers for the three drug classes. A number of genetic variations have been investigated so far. The explored candidate genes mostly encode drug targets, drug-metabolizing enzymes, and genes linked to T2D risk. Although many of the results are promising, it is still necessary to obtain more information from larger controlled studies to confirm their clinical significance. This approach may lead towards more personalized treatment for patients with T2D.</p> Selma Imamovic Kadric Aida Kulo Cesic Tanja Dujic Copyright (c) 2021 Selma Imamovic Kadric, Aida Kulo Cesic, Tanja Dujic https://creativecommons.org/licenses/by/4.0 2021-04-20 2021-04-20 21 3 10.17305/bjbms.2021.5646 Analysis of the diagnostic and prognostic value of miR-9-5p in carotid artery stenosis https://www.bjbms.org/ojs/index.php/bjbms/article/view/5545 <p>More and more evidence shows that microRNAs (miRNAs) play an important role in the diagnosis and prognosis of human diseases. In this study, we investigated the diagnostic value of miR-9-5p for asymptomatic carotid artery stenosis (CAS) and its predictive value for future cerebrovascular events within 5 years. A total of 88 asymptomatic CAS patients and 86 healthy individuals were recruited. The expression level of serum miR-9-5p was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic value of miR-9-5p in CAS was assessed by a receiving operator characteristic (ROC) curve. The predictive value of miR-9-5p for the occurrence of cerebrovascular events was evaluated by the Kaplan-Meier method. The serum level of miR-9-5p was significantly decreased in asymptomatic CAS patients. ROC curve had an AUC value of 0.910, with the sensitivity and specificity of 80.7% and 87.2% at the cut-off value of 0.72, respectively. A total of 25 patients had cerebrovascular events during the 5-year follow-up, including 3 strokes and 22 transient ischemic attacks<strong>&nbsp;</strong>(TIAs). Kaplan-Meier survival analysis revealed that the low expression level of miR-9-5p was an independent factor closely related to the occurrence of cerebrovascular events. Serum miR-9-5p could be used as a new biomarker for the diagnosis of CAS, and the low expression of miR-9-5p is associated with poor prognosis.</p> Hongxin Liu Juan Zhou Wei Jiang Feng Wang Copyright (c) 2021 Hongxin Liu, Juan Zhou, Wei Jiang, Feng Wang https://creativecommons.org/licenses/by/4.0 2021-04-19 2021-04-19 21 3 10.17305/bjbms.2021.5545