Chemical Composition and Neuroprotective Properties of Indonesian Stingless Bee (Geniotrigona thoracica) Propolis Extract in an In-Vivo Model of Intracerebral Hemorrhage (ICH).

Stroke is the world's second-leading cause of death. Current treatments for cerebral edema following intracerebral hemorrhage (ICH) mainly involve hyperosmolar fluids, but this approach is often inadequate. Propolis, known for its various beneficial properties, especially antioxidant and anti-inflammatory properties, could potentially act as an adjunctive therapy and help alleviate stroke-associated injuries. The chemical composition of Geniotrigona thoracica propolis extract was analyzed by GC-MS after derivatization for its total phenolic and total flavonoid content. The total phenolic content and total flavonoid content of the propolis extract were 1037.31 ± 24.10 µg GAE/mL and 374.02 ± 3.36 µg QE/mL, respectively. By GC-MS analysis, its major constituents were found to be triterpenoids (22.4% of TIC). Minor compounds, such as phenolic lipids (6.7% of TIC, GC-MS) and diterpenic acids (2.3% of TIC, GC-MS), were also found. Ninety-six Sprague Dawley rats were divided into six groups; namely, the control group, the ICH group, and four ICH groups that received the following therapies: mannitol, propolis extract (daily oral propolis administration after the ICH induction), propolis-M (propolis and mannitol), and propolis-B+A (daily oral propolis administration 7 days prior to and 72 h after the ICH induction). Neurocognitive functions of the rats were analyzed using the rotarod challenge and Morris water maze. In addition, the expression of NF-κB, SUR1-TRPM4, MMP-9, and Aquaporin-4 was analyzed using immunohistochemical methods. A TUNEL assay was used to assess the percentage of apoptotic cells. Mannitol significantly improved cognitive-motor functions in the ICH group, evidenced by improved rotarod and Morris water maze completion times, and lowered SUR-1 and Aquaporin-4 levels. It also significantly decreased cerebral edema by day 3. Similarly, propolis treatments (propolis-A and propolis-B+A) showed comparable improvements in these tests and reduced edema. Moreover, combining propolis with mannitol (propolis-M) further enhanced these effects, particularly in reducing edema and the Virchow-Robin space. These findings highlight the potential of propolis from the Indonesian stingless bee, Geniotrigona thoracica, from the Central Tapanuli region as a neuroprotective, adjunctive therapy.

Combined Aerobic Exercise with Intermittent Fasting Is Effective for Reducing mTOR and Bcl-2 Levels in Obese Females.

The integration of combined aerobic exercise and intermittent fasting (IF) has emerged as a strategy for the prevention and management of obesity, including its associated health issues such as age-related metabolic diseases. This study aimed to examine the potential of combined aerobic exercise and IF as a preventative strategy against cellular senescence by targeting mTOR and Bcl-2 levels in obese females. A total of 30 obese women, aged 23.56 ± 1.83 years, body fat percentage (FAT) 45.21 ± 3.73% (very high category), BMI 30.09 ± 3.74 kg/m2 were recruited and participated in three different types of interventions: intermittent fasting (IF), exercise (EXG), and a combination of intermittent fasting and exercise (IFEXG). The intervention program was carried out 5x/week for 2 weeks. We examined mTOR and Bcl-2 levels using ELISA kits. Statistical analysis used the one-way ANOVA test and continued with Tukey's HSD post hoc test, with a significance level of 5%. The study results showed that a combination of aerobic exercise and IF significantly decreased mTOR levels (-1.26 ± 0.79 ng/mL) compared to the control group (-0.08 ± 1.33 ng/mL; p ≤ 0.05). However, combined aerobic exercise and IF did not affect Bcl-2 levels significantly (-0.07 ± 0.09 ng/mL) compared to the control group (0.01 ± 0.17 ng/mL, p ≥ 0.05). The IF-only group, exercise-only group, and combined group all showed a significant decrease in body weight and fat mass compared to the control group (p ≤ 0.05). However, the combined aerobic exercise and IF program had a significant effect in reducing the total percentage of body fat and fat mass compared to the IF-only group (p ≤ 0.05). Therefore, it was concluded that the combined intermittent fasting and exercise group (IFEXG) undertook the most effective intervention of the three in terms of preventing cellular senescence, as demonstrated by decreases in the mTOR level, body weight, and fat mass. However, the IFEXG did not present reduced Bcl-2 levels.

Epidemiology of cleft lip and palate charity mission surgery at Bandung Cleft Lip and Palate Center, Indonesia: a 14-year institutional review.

BACKGROUND: The management of cleft lip and palate aims at improving the patient's aesthetic and functional outcomes. Delaying primary repair can disrupt the patient's functional status. Long-term follow-up is essential to evaluate the need for secondary repair or revision surgery. This article presents the epidemiology of cleft lip and palate, including comprehensive patient characteristics, the extent of delay, and secondary repair at our institutional center, the Bandung Cleft Lip and Palate Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia. METHODS: This retrospective study aimed to determine the epidemiology and recurrence rates of cleft lip and palate at the Bandung Cleft Lip and Palate Center, Indonesia, from January 2007 to December 2021. The inclusion criteria were patients diagnosed with cleft lip and/or palate. Procedures such as labioplasty, palatoplasty, secondary lip and nasal repair, and alveolar bone grafting were performed, and data on recurrence were available. RESULTS: In total, there were 3,618 patients with cleft lip and palate, with an age range of 12 months to 67 years. The mean age was 4.33 years, and the median age was 1.35 years. Males predominated over females in all cleft types (60.4%), and the cleft lip was on the left side in 1,677 patients (46.4%). Most cases were unilateral (2,531; 70.0%) and complete (2,349; 64.9%), and involved a diagnosis of cleft lip and palate (1,981; 54.8%). CONCLUSION: Delayed primary labioplasty can affect daily functioning. Primary repair for patients with cleft lip and palate may be postponed due to limited awareness, socioeconomic factors, inadequate facilities, and varying adherence to treatment guidelines. Despite variations in the timing of primary cleft lip repair (not adhering to the recommended protocol), only 10% of these patients undergo reoperation. Healthcare providers should prioritize the importance of the ideal timing for primary repair in order to optimize physiological function without compromising the aesthetic results.

Effect of Low Protein Diet on Bone Structure of Young Wistar Mice.

<b>Background and Objective:</b> Malnutrition and stunting are major unresolved problems in Indonesia. Protein deficiency can cause stunted growth, as well as make physical and cognitive abilities cannot reach their maximum potential. During childhood the need for protein must be fulfilled so that the peak of bone formation during adolescence can be perfect. In malnourished children, a low protein diet will lead to thinning of the bone cortex. Due to the high rate of stunting and malnutrition in children due to protein deficiency, a study was conducted on the effects of feeding low protein diet on rat bones. <b>Materials and Methods:</b> Male Wistar rats (n = 10) at 6-8 weeks old (body weight around 250 g), control groups were fed a normal chow diet and low protein diet groups were given low protein chow diet (protein 5%) for 18 weeks, then the rats were sacrificed and the femoral bones were isolated. Body weight, femur weight, femur length were checked and bone density was examined using X-ray. <b>Results:</b> The body proportions of the low protein group rats were smaller and thinner than those of the control group. This difference is supported by the significant weight loss starting from the sixth week after low protein feeding. There are significant differences in body weight and femur weight between the control and low protein diet groups. Bone density decreases significantly in low protein diet group. Macroscopically, the femur length of the low protein group was shorter than the control group, however the femur length did not show significant differences statistically between the two groups. <b>Conclusion:</b> A low protein diet decreased the body weight of the rats, also causing impaired bone growth characterized by decreasing femur weight. The low protein diet also caused osteoporosis in the bones.

Translocator Protein 18 kDa (TSPO): A Promising Molecular Target for Image-Guided Surgery of Solid Cancers.

The translocator protein 18-kDa (TSPO) is a mitochondrial membrane protein that is previously identified as the peripheral benzodiazepine receptor (PBR). Furthermore, it plays a significant role in a diverse range of biochemical processes, including steroidogenesis, mitochondrial cholesterol transport, cell survival and death, cell proliferation, and carcinogenesis. Several investigations also reported its roles in various types of cancers, including colorectal, brain, breast, prostate, and lung cancers, as well as melanoma. According to a previous study, the expression of TSPO was upregulated in cancer cells, which corresponds to an aggressive phenotype and/or poor prognosis. Consequently, the potential for crafting diagnostic and prognostic tools with a focus on TSPO holds great potential. In this context, several radioligands designed to target this protein have been identified, and some of the candidates have advanced to clinical trials. In recent years, the use of hybrid probes with radioactive and fluorescence molecules for image-guided surgery has exhibited promising results in animal and human studies. This indicates that the approach can serve as a valuable surgical navigator during cancer surgery. The current hybrid probes are built from various molecular platforms, including small molecules, nanoparticles, and antibodies. Although several TSPO-targeted imaging probes have been developed, their development for image-guided surgery of cancers is still limited. Therefore, this review aims to highlight recent findings on the involvement of TSPO in carcinogenesis, as well as provide a new perspective on the potential application of TSPO-targeted hybrid probes for image-guided surgery.

Alliaxylines A-E: five new mexicanolides from the stem barks of Dysoxylum alliaceum (Blume) Blume ex A.Juss.

A total of five new mexicanolides (1-5), namely alliaxylines A-E, together with two known limonoids 6 and 7, were isolated and identified from Dysoxylum alliaceum (Blume) Blume ex. A.Juss. (Meliaceae). The structures of these compounds were elucidated based on extensive spectroscopic analyses, including HR-ESI-MS, UV, IR, 1D, and 2D NMR, as well as theoretical stimulation of NMR shifts with the DP4 + algorithm. Consequently, this study aimed to examine cytotoxic activities of these compounds against MCF-7 and A549 cell lines. The results implied that compound 2 was the most potent against the two tested cells, with IC50 values of 34.95 ± 0.21 and 44.39 ± 1.03 µM.

Pharmacological Activity of Chemical Compounds of Potato Peel Waste (Solanum tuberosum L.) in vitro: A Scoping Review.

Introduction: The potato (Solanum tuberosum L.) is a short-lived tuber plant with a round to oval shape and varying colors, depending on the variety. It is known that only the inside of the potato is used, while the peel is generally discarded. However, recent studies have shown that potato peels contain many health-beneficial compounds. Purpose: This study aimed to investigate the compounds present in potato peels and their in vitro activities. Methods: A scoping review following the PRISMA guidelines was conducted. The selection process involved identifying articles of in vitro research published within the last 10 years (2012-2022). Electronic searches were conducted using the portals Scopus, ScienceDirect, EBSCOhost, and Portal Garuda by using the keywords "potato" or "Solanum tuberosum" and "peel" or "skin". The search was limited to articles in English with full text availability. Results: The screening process resulted in a total of 4773 articles from the four search engines; 14 articles were obtained that met the requirements for the review, most of which use extract preparations in their research. Extracts of flavonoids, phenols, and glycoalkaloids are the most frequently studied compounds, and their antioxidant and anti-inflammatory activity have undergone extensive research. Conclusion: The potential compounds contained in potato peels, including flavonoids, phenols, and glycoalkaloids, are highly abundant and offer numerous benefits. Provides opportunities for further research to prove the potential pathway activity of the compound. These compounds have been the subject of extensive research, suggesting their significance in the context of health and nutrition.

Carotenoids in red fruit (Pandanus conoideus Lam.) have a potential role as an anti­pigmentation agent (Review).

Melasma is a persistent condition characterized by excessive melanin production in the skin. The management of melasma necessitates a protracted treatment duration, which is associated with diminished levels of patient satisfaction. One effective strategy for mitigating occurrence of melasma is consumption of nutricosmetics with depigmentation properties. The present review aimed to investigate the potential of red fruit as a depigmentation agent. Carotenoids serve a crucial role in human nutrition as a precursor to vitamin A. Carotenoids serve as scavengers of reactive oxygen species generated by ultraviolet radiation. Carotenoids promote skin health. Red fruit, a fruit originating from Papua (Indonesia) has anti-pigmentation properties associated with its ability to block melanogenesis through various protein pathways such as PKA, ERK, and AKT signaling pathways. The consumption of food rich in carotenoids, such as red fruit, has advantageous properties to reduce hyperpigmentation and skin brightening.

Refining macrostomia correction: Case series applying square flap technique and Z/W-plasty skin closure for enhanced aesthetic and functional outcome.

INTRODUCTION AND IMPORTANCE: Macrostomia is a congenital deformity found in Tessier no. 7 facial clefts defined as an enlargement of the mouth at the oral commissure. Several techniques are described in literature to achieve optimal functional and aesthetic results, with varying results and surgeon preferences. In this case series we report surgical repair of macrostomia with a vermillion square flap method for the oral commissure combined with either Z-plasty or W-plasty closure for the skin. CASES PRESENTATION: A retrospective case analysis of 12 patients with macrostomia operated over the past 7 years at our plastic surgery division was performed (by two different operators; 11 cases by A.S. and 1 case by R.S.). Clinical features of the patients were analyzed through photography documentation, and patient description such as age of operation, operation technique, and complications were obtained through patient records. Macrostomia was corrected with a vermillion square flap method for commissure, overlapping muscle closure, along with either Z-plasty or W-plasty closure for the skin. Quality of lip commissure position, symmetry, thickness of vermillion, and scar result were recorded. CLINICAL DISCUSSION: In all twelve patients repaired with the overlapping muscle closure and square flap, the lip commissures were formed with satisfactory shape, position, and thickness with no commissure contracture during the follow up period. The Z-plasty was a simpler method compared to the W-plasty, and resulted in comparable scars. One patient (adult with hemifacial macrostomia and W-plasty skin closure) underwent revision surgery for more accurate symmetry and position of the oral commissure. CONCLUSION: There are many varieties of surgical repair for macrostomia, and each method should be adjusted and combined according to each patient. Overall, macrostomia repair with this technique combination produced satisfactory aesthetic and functional results in all twelve patients. Z-plasty for skin closure after muscle and vermillion closure was a simpler technique and resulted in comparable scars than W-pasty closure in this case series.

Research Trends in Molecular Biological Studies on Oral Squamous Cell Carcinoma: A Bibliometric Analysis.

Background: Since the discovery of PCR and ELISA, in vitro research in the realm of molecular biology pertaining to oral squamous cell carcinoma (OSCC) has witnessed significant expansion. Objective: to provide a comprehensive overview of molecular biology research on OSCC through visual mapping techniques. Methods: We conducted an analysis of publications within the "oral squamous cell carcinoma" category from Scopus' core collection. On 20 January 2023, we screened these publications using an advanced search employing the keywords "oral squamous cell cancer" and "cell line." Data analysis was performed using Microsoft Excel 2010 and VOSviewer, facilitating the examination of author contributions, journal productivity, institutional affiliations, and contributions by nations. VOSviewer was further utilized for co-occurrence and reference analysis of keywords. Results: A total of 781 papers spanning from 1992 to 2023 were collected. Notably, Japan, China, and the United States emerged as significant contributors in this field. The Osaka University Graduate School of Dentistry (Japan) ranked first with 21 publications. Chae J-I of Chonbuk National University (South Korea) emerged as the most prolific author, with 14 publications. The International Journal of Oncology and the Journal of Oral Pathology and Medicine were identified as the two most prolific journals. The central themes that emerged were epidermal growth factor receptor, invasion, epithelial-mesenchymal transition, angiogenesis, apoptosis, and metastasis. Conclusion: The rate of publications focused on the molecular biology of OSCC has seen a remarkable increase. Research priorities have shifted from topics such as "radiation, RANKL, cyclin D1, RNA interference, and matrix metalloproteinase" to encompass areas such as "chemoresistance due to cisplatin, other therapeutic agents (metformin and monoclonal antibody), autophagy, inflammation, microRNA, cancer-associated fibroblasts, and STAT3 (with roles in cell migration and tumorigenesis)." These seven significant future research areas hold promise in identifying reliable biological markers for oral cancer detection and treatment, thereby improving clinical outcomes.

New hybrid radio-fluorescent probes [131I]-BPF-01 and [131I]-BPF-02 for visualisation of cancer cells: Synthesis and preliminary in vitro and ex vivo evaluations.

We synthesised and biologically evaluated two new hybrid probes [131I]BPF-01 and [131I]BPF-02 which were built from three structural entities: benzothiazole-phenyl, fluorescein isothiocyanate (FITC), and iodine-131. These probes were designed for potential applications in assisting surgical procedures of solid cancers. The cytotoxicity study demonstrated that fluorescent probes BPF-01 (31.23 µg/mL) and BPF-02 (250 µg/mL) were relatively not toxic to normal immortalized human keratinocytes (HaCaT) cells, as indicated by the percentage of cell survival above 50 %. Furthermore, both probes displayed low to moderate anticancer activity against the breast cancer cells (MDA-MB-231) and prostate cancer cells (LNCaP and DU-145). The probe BPF-01 apparently showed an accumulation in the tumour tissues, as suggested by ex vivo fluorescence examinations. In addition, the cellular uptake study suggests that hybrid probe [131I]-BPF-01 was potentially accumulated in the MCF-7 cell line with the highest uptake of 16.11 ± 1.52 % after 2 h of incubation, approximately 50-fold higher than the accumulation of iodine-131 (control). The magnetic bead assay suggests that [131I]-BPF-02 and [131I]-BPF-02 showed a promising capability to interact with translocator protein 18 kDa (TSPO). Moreover, the computational data showed that the binding scores for ligands 7-8, BPF-01 and BPF-02, and [131I]-BPF-01 and [131I]-BPF-02 in the TSPO were considerably high. Accordingly, fluorescent probes BPF-01 and BPF-02, and hybrid probes [131I]BPF-01 and [131I]BPF-02 can be further developed for targeting cancer cells during intraoperative tumour surgery.

The predictive value of infrared thermal imaging (IRT) for peripheral artery disease: A systematic review.

BACKGROUND: Medical infrared thermal imaging (IRT) has been applied to research blood flow, breast cancer detection, and human body muscle performance. The benefits of IRT include the fact that it is noninvasive, quick, dependable, non-contact, capable of creating several recordings in a short period of time, and secure for both patients and medical professionals. We aimed to determine the predictive value of IRT for identifying and evaluating any interventional procedure in patients affected by peripheral artery disease (PAD) of any severity. METHODS: We searched the Cochrane Library, EMBASE, and PubMed on the topic of IRT and PAD until January 20,2023. We excluded gray literature as it is lacking credibility for not undergoing a peer-reviewed process. The search strategy includes the medical topic headings for "infrared thermal imaging" and "peripheral vascular disorders." The primary outcome of this systematic review was the variation in tissue perfusion in PAD patients. Each technique's technical characteristics and therapeutic use within PAD must be described in each included study. RESULTS: This systematic review included 2 case reports and 3 observational studies. By comparing the temperatures of PAD patients hands, legs, and feet, IRT might prove to be an unduly valuable tool for treating vascular illnesses, especially in light of the knowledge gained from the temperature distribution maps. CONCLUSION: This noninvasive method demonstrated encouraging results in the detection of various areas of foot perfusion and the screening of PAD, and it gave good findings in gauging the effects of any type of intervention.

Exercise intensities modulate ACE2/MasR/eNOS pathway in male Wistar rat's lung.

Specific exercise intensities could improve lung vascular function by increasing nitric oxide (NO). The ACE2/MasR/eNOS axis is one of the pathways facilitating NO synthesis. This study examines the effect of different intensities of aerobic training on the ACE2/MasR/eNOS axis and histology of lung muscular arteries. Male Wistar rats were used in this study and randomized into control and exercise groups receiving low-, moderate-, and high-intensity training. The training was conducted for 30 min daily, five times a week, for 8 weeks. We observed that different exercise intensities affect the ACE2/MasR/eNOS pathway differently. Compared to control, high-intensity aerobic exercise significantly increased ACE2, Mas receptor (MasR), and eNOS mRNA expressions (p < 0.01). Moderate-intensity exercise significantly increased MasR and eNOS mRNA expressions compared to the control (p < 0.05), and this intensity also increased ACE2 mRNA but not significantly. Low-intensity exercise increased ACE2, MasR, and eNOS mRNA expressions but not significantly. Low-, moderate-, or high-intensity exercises reduced the medial wall thickness of the lung muscular arteries but not significantly. In conclusion, high-intensity exercise may induce NO synthesis in the lung by increasing mRNA expression of ACE2, MasR, and eNOS without decreasing the medial wall thickness of the muscular artery. Thus, high-intensity exercise may be the optimal intensity to improve NO synthesis and vascular function in the lung.

Understanding the Roles of Selenium on Thyroid Hormone-Induced Thermogenesis in Adipose Tissue.

Brown adipose tissue (BAT) and white adipose tissue (WAT) are known to regulate lipid metabolism. A lower amount of BAT compared to WAT, along with adipose tissue dysfunction, can result in obesity. Studies have shown that selenium supplementation protects against adipocyte dysfunction, decreases WAT triglycerides, and increases BAT triiodothyronine (T3). In this review, we discuss the relationship between selenium and lipid metabolism regulation through selenoprotein deiodinases and the role of deiodinases and thyroid hormones in the induction of adipose tissue thermogenesis. Upon 22 studies included in our review, we found that studies investigating the relationship between selenium and deiodinases demonstrated that selenium supplementation affects the iodothyronine deiodinase 2 (DIO2) protein and the expression of its associated gene, DIO2, proportionally. However, its effect on DIO1 is inconsistent while its effect on DIO3 activity is not detected. Studies have shown that the activity of deiodinases especially DIO2 protein and DIO2 gene expression is increased along with other browning markers upon white adipose tissue browning induction. Studies showed that thermogenesis is stimulated by the thyroid hormone T3 as its activity is correlated to the expression of other thermogenesis markers. A proposed mechanism of thermogenesis induction in selenium supplementation is by autophagy control. However, more studies are needed to establish the role of T3 and autophagy in adipose tissue thermogenesis, especially, since some studies have shown that thermogenesis can function even when T3 activity is lacking and studies related to autophagy in adipose tissue thermogenesis have contradictory results.

Chitosan/Alginate Polymeric Nanoparticle-Loaded α-Mangostin: Characterization, Cytotoxicity, and In Vivo Evaluation against Breast Cancer Cells.

α-mangostin (Amg), a compound isolated from the mangosteen rind (Garcinia mangostana, L.), has demonstrated promising anticancer activity. However, its low solubility and selectivity against cancer cells limit its efficacy. To address this issue, researchers have developed chitosan/alginate polymeric nanoparticles (NANO-AMCAL) to enhance the effectiveness of Amg. In vitro studies have demonstrated that NANO-AMCAL is highly active against breast cancer cells. Therefore, an in vivo study was conducted to evaluate the efficacy of NANO-AMCAL in treating breast cancer in Wistar rats (Rattus norvegicus) and determine the effective dose. The rats were divided into seven treatment groups, including positive control, negative control, pure Amg, and NANO-AMCAL 5 mg, 10 mg, and 20 mg. The rats were injected subcutaneously with a carcinogenic agent, 7,12-dimethylbenz(a)anthracene (DMBA) and were evaluated for weight and tumor volume every three days during treatment. Surgery was performed on day 14, and histopathological studies were carried out on breast and lung cancer tissues. The results showed that NANO-AMCAL significantly enhanced the anticancer activity of Amg in treating breast cancer in Wistar rats. NANO-AMCAL containing 0.33 mg of Amg had a healing effect three times better than 20 mg pure Amg and was comparable to tamoxifen. The effective dose of NANO-AMCAL for anti-breast cancer treatment in Wistar rats was found to be 20 mg, which exhibited a good healing response, and the tumor volume continued to decrease up to 17.43% on the 14th day. Furthermore, histopathological tests showed tissue repair and no metastases. These findings suggest that NANO-AMCAL may be a promising therapeutic option for breast cancer treatment.

The pathology of oxidative stress-induced autophagy in a chronic rotator cuff enthesis tear.

Partial-thickness rotator cuff tears (PTRCTs) are often found in daily orthopedic practice, with most of the tears occurring in middle-aged patients. An anaerobic process and imbalanced oxygenation have been observed in PTRCTs, resulting in oxidative stress. Studies have shown the roles of oxidative stress in autophagy and the potential of unregulated mechanisms causing disturbance in soft tissue healing. This article aims to review literature works and summarize the potential pathology of oxidative stress and unregulated autophagy in the rotator cuff enthesis correlated with chronicity. We collected and reviewed the literature using appropriate keywords, in addition to the manually retrieved literature. Autophagy is a normal mechanism of tissue repair or conversion to energy needed for the repair of rotator cuff tears. However, excessive mechanisms will degenerate the tendon, resulting in an abnormal state. Chronic overloading of the enthesis in PTRCTs and the hypovascular nature of the proximal tendon insertion will lead to hypoxia. The hypoxia state results in oxidative stress. An autophagy mechanism is induced in hypoxia via hypoxia-inducible factors (HIFs) 1/Bcl-2 adenovirus E1B 19-kDa interacting protein (BNIP) 3, releasing beclin-1, which results in autophagy induction. Reactive oxygen species (ROS) accumulation would induce autophagy as the regulator of cell oxidation. Oxidative stress will also remove the mammalian target of rapamycin (mTOR) from the induction complex, causing phosphorylation and initiating autophagy. Hypoxia and endoplasmic reticulum (ER) stress would initiate unfolded protein response (UPR) through protein kinase RNA-like ER kinase (PERK) and activate transcription factor 4, which induces autophagy. Oxidative stress occurring in the hypovascularized chronic rotator cuff tear due to hypoxia and ROS accumulation would result in unregulated autophagy directly or autophagy mediated by HIF-1, mTOR, and UPR. These mechanisms would disrupt enthesis healing.

Detection of Human Herpesviruses in Sera and Saliva of Asymptomatic HIV-Infected Individuals Using Multiplex RT-PCR DNA Microarray.

Human herpesviruses (HHVs) are frequently linked to an increased risk of acquiring human immunodeficiency virus (HIV), and vice versa. This study aimed to detect human herpesvirus (HHV) members in the sera and saliva of asymptomatic HIV-infected individuals. Paired saliva and serum samples were obtained from 30 asymptomatic HIV-infected individuals. HHVs were detected with a multiplex reverse transcription-polymerase chain reaction (RT-PCR) DNA microarray Clart®Entherpex kit. A total of 30 subjects were enrolled: 23 (76.67%) men and 7 (23.33%) women. The present study showed that at least one or more HHV members were detected in the saliva and sera of all (100%) of the subjects. In the saliva, we detected herpes simplex virus 1 (HSV-1) 6.67%, herpes simplex virus 2 (HSV-2) 6.67%, Epstein-Barr virus (EBV) 86.67%, cytomegalovirus (CMV) 63.33%, HHV-6 (40%), and HHV-7 (83.33%). In the sera, HSV-2 (20%), EBV (30%), CMV (40%), HHV-6 (0%), and HHV-7 (76.67%) were found, but not HSV-1. VZV and HHV-8 were not detected in either the saliva or sera. EBV and HHV6 were significantly more prevalent in the saliva than they were in the sera of asymptomatic HIV-infected individuals (p < 0.05). However, no significant differences were found in the prevalence of HSV-1, EBV, CMV, HHV-6, and HHV-7 in the saliva and sera of asymptomatic HIV-infected individuals (p > 0.05). In conclusion, the multiplex RT-PCR DNA microarray can serve as a valuable diagnostic tool that can be used as a screening tool or a first-line test for HHVs infections.

Propolis-Based Nanostructured Lipid Carriers for α-Mangostin Delivery: Formulation, Characterization, and In Vitro Antioxidant Activity Evaluation.

α-Mangostin (a xanthone derivative found in the pericarp of Garcinia mangostana L.) and propolis extract (which is rich in flavonoids and phenols) are known for their antioxidant properties, making them potential supplements for the treatment of oxidative stress-related conditions. However, these two potential substances have the same primary drawback, which is low solubility in water. The low water solubility of α-mangostin and propolis can be overcome by utilizing nanotechnology approaches. In this study, a propolis-based nanostructured lipid carrier (NLC) system was formulated to enhance the delivery of α-mangostin. The aim of this study was to characterize the formulation and investigate its influence on the antioxidant activity of α-mangostin. The results showed that both unloaded propolis-based NLC (NLC-P) and α-mangostin-loaded propolis-based NLC (NLC-P-α-M) had nanoscale particle sizes (72.7 ± 1.082 nm and 80.3 ± 1.015 nm, respectively), neutral surface zeta potential (ranging between +10 mV and -10 mV), and good particle size distribution (indicated by a polydispersity index of <0.3). The NLC-P-α-M exhibited good entrapment efficiency of 87.972 ± 0.246%. Dissolution testing indicated a ~13-fold increase in the solubility of α-mangostin compared to α-mangostin powder alone. The incorporation into the propolis-based NLC system correlated well with the enhanced antioxidant activity of α-mangostin (p < 0.01) compared to NLC-P and α-mangostin alone. Therefore, the modification of the delivery system by incorporating α-mangostin into the propolis-based NLC overcomes the physicochemical challenges of α-mangostin while enhancing its antioxidant effectiveness.

Aerobic Exercise versus Electronic Cigarette in Vascular Aging Process: First Histological Insight.

Smoking is related to vascular aging. However, the hazardous effect of e-cigarette is often debatable, with limited studies available. In contrast, moderate-intensity aerobic exercise is well known to decrease aortic stiffness. We provide novel research to determine the effect of e-cigarette and aerobic moderate-intensity exercise on the aortic structure of Wistar rats. A total of 26 male Wistar rats (Rattus norvegicus) 8 weeks aged, 200-250 g b.w., were randomly divided into 4 groups, namely, K0 (normal rats), K1 (rats were given moderate-intensity aerobic exercise by animal treadmill 20 m/30 min), K2 (rats were given e-cigarette with 6 mg nicotine, 40% propylene glycol, and 60% vegetable glycerine 30 min for 5 days/week), and K3 (rats were given e-cigarette and moderate-intensity aerobic exercise). After exposure for 6 weeks, all animals were sacrificed to isolate the aorta for histopathological analysis with hematoxylin-eosin stain to evaluate the elastic fiber layer and intimal-medial thickness. The Verhoeff-Van Gieson staining was done for quantification elastic lamina fragmentation. Our study found that the e-cigarette group had the highest elastic lamina fragmentation among groups (8.14 ± 2.85). The exercise only group showed the lowest elastic lamina fragmentation (2.50 ± 1.87). Fragmentation in the e-cigarette and exercise group was higher than in the exercise only group (5.83 ± 0.753 vs. 2.50 ± 1.87, p = 0.002). There is a significant difference of NO serum between four groups. The result of post hoc analysis using LSD showed that there is a significant difference of NO serum between K0 and K2, K0 and K3, K1 and K2, and K1 and K3. Therefore, our research demonstrated that the most injury of aorta elastic lamina was in the group that was exposed to e-cigarette that leads to vascular aging while exercise is not yet proven to reverse this effect.

V-ATPase subunit C 1 and IKBIP as tandem prospective biomarkers for diabetic nephropathy.

AIMS: The appearance of low-molecular-weight (LMW) protein in the urine indicates any disruption in the structural integrity of the glomerular capillary wall; therefore, the presence of LMW protein may be a potential predictive marker for DN. METHODS: The urine proteomic profiling of T2DM patients (n = 94) and control group (n = 32) was compared by liquid chromatography-tandem mass spectrometry, and the untargeted LMW protein was identified by Progenesis Q1 For Proteomics v4.2. RESULTS: A total of 73 LMW proteins were identified and quantified, of which, 32 proteins were found to be altered significantly (p < 0.05). Further analysis with heat maps identified two potential proteins with the highest folding alterations in urine. V-ATPase subunit C 1 abundance was significantly inversely correlated with microalbumin and significantly decreased in urine, whereas increased IKBIP was positively correlated with microalbumin. The level of those proteins was significantly different among the control, T2DM, and DN groups, implying an association with the progression of DN. CONCLUSIONS: The present findings of our study indicate that the decreasing V-ATPase subunit C 1 together with increasing IKBIP in urine, were found to be closely associated with DN complications and signifying their value as biomarkers for predicting the risk of DN at initial diagnosis.