miR4352b a cross-species modulator of SOSTDC1, targets dual pathway to regulate bone health and fracture healing.

Mutations in SOST can lead to various monogenic bone diseases. Its paralog, SOSTDC1, shares 55 % protein sequence homology and belongs to the BMP antagonist class. Sostdc1-/- mice exhibit distinct effects on cortical and trabecular bone. Genetic polymorphisms in SOSTDC1 impacting peak bone mass makes SOSTDC1 gene, a candidate for influencing BMD variation in humans. SOSTDC1 is upregulated in bone loss conditions, altering BMP-responsive genes and signaling modulators, suggesting its dual BMP/Wnt antagonist role may enhance both pathways. Overexpression of SOSTDC1 confirmed its role as an osteogenic antagonist. Glycine max (Soy)-derived miR4352b, identified for cross-kingdom applications, precisely targets SOSTDC1, a key regulator of bone. SOSTDC1 competitively binds to BMP2 receptor, BMPR1A. Gma-miR4352b suppresses SOSTDC1 expression, enhancing osteogenesis and countering SOSTDC1's inhibition of osteogenic potential. Modeling estrogen deficiency to mimic elevated SOSTDC1 levels, we observed an inverse correlation with SOSTDC1 expression, while serum BMP2 and PINP levels increased following gma-miR4352b supplementation. In fracture healing, SOSTDC1's crucial role becomes evident in conditions of delayed fracture healing. As healing progresses, SOSTDC1 expression decreases. Gma-miR4352b, compared to scrambled miRNA, remarkably promotes callus formation, achieving 68 % healing by day 10, surpassing the scrambled group at 44 %. By the day 13, the treatment group exhibits advanced healing, challenging to find the callus, while the scrambled group maintains a healing rate similar to day10. The accelerated healing in the treatment group underscores the importance of SOSTDC1 in influencing early fracture healing, potentially through the activation of both BMP2 and Wnt signaling pathways.

Flavopiridol inhibits adipogenesis and improves metabolic homeostasis by ameliorating adipose tissue inflammation in a diet-induced obesity model.

Repositioning of FDA approved/clinical phase drugs has recently opened a new opportunity for rapid approval of drugs, as it shortens the overall process of drug discovery and development. In previous studies, we predicted the possibility of better activity profiles of flavopiridol, the FDA approved orphan drug with better fit value 2.79 using a common feature pharmacophore model for anti-adipogenic compounds (CFMPA). The present study aimed to investigate the effect of flavopiridol on adipocyte differentiation and to determine the underlying mechanism. Flavopiridol inhibited adipocyte differentiation in different cell models like 3T3-L1, C3H10T1/2, and hMSCs at 150 nM. Flavopiridol was around 135 times more potent than its parent molecule rohitukine. The effect was mediated through down-regulation of key transcription factors of adipogenesis i.e. Peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and their downstream targets, including adipocyte protein -2 (aP2) and fatty acid synthase (FAS). Further, results revealed that flavopiridol arrested the cell cycle in G1/S phase during mitotic clonal expansion by suppressing cell cycle regulatory proteins i.e. Cyclins and CDKs. Flavopiridol inhibited insulin-stimulated signalling in the early phase of adipocyte differentiation by downregulation of AKT/mTOR pathway. In addition, flavopiridol improved mitochondrial function in terms of increased oxygen consumption rate (OCR) in mature adipocytes. In the mouse model of diet-induced obesity, flavopiridol attenuated obesity-associated adipose tissue inflammation and improved serum lipid profile, glucose tolerance as well as insulin sensitivity. In conclusion, the FDA approved drug flavopiridol could be placed as a potential drug candidate for the treatment of cancer and obesity comorbid patients.

Anti-adipogenic action of a novel oxazole derivative through activation of AMPK pathway.

Obesity is a chronic disorder with multifactorial etiology, including genetic, medical, dietary and other environmental factors. Both natural and synthetic heterocyclic compounds, especially oxazoles, represent an interesting group of compounds and have gained much attention due to their remarkable biological activities. Therefore, a library of 3,3-DMAH (3,3-dimethylallylhalfordinol) inspired N-alkylated oxazole bromide salts with varied substitutions were prepared and screened using the 3T3-L1 model of adipogenesis and HFD-induced obesity model in Syrian golden hamsters. Several compounds in the synthesized series displayed remarkable anti-adipogenic potential on the differentiation of 3T3-L1 preadipocytes. Compound 19e, displayed the most potent activity of all and selected for further studies. Compound 19e inhibited mitotic clonal expansion of 3T3-L1 cells and enhanced the mitochondrial oxygen consumption rate of the cells during early phase of differentiation via AMPK activation. 19e also improved the dyslipidaemia in high calorie diet fed Syrian Golden Hamsters. Therefore, compound 19e can serve as a potential lead against adipogenesis and dyslipidaemia models and could be further investigated to affirm its significance as a drug candidate.

Persistent Lack of Female Orthopaedic Sports Medicine Fellows.

Purpose: To evaluate the gender composition of fellows, faculty, and leaders within orthopaedic sports medicine fellowship programs to provide a more complete description of gender diversity within this subspecialty. Methods: Official program websites of orthopaedic sports medicine fellowships listed on the Arthroscopy Association of North America fellowship directory were examined. Data collected for analysis included the gender of program directors, fellowship faculty, orthopaedic surgery department faculty, current sports medicine fellows, and fellows who graduated within the last 5 years. Results: Of the 132 orthopaedic sports medicine fellows in training in the United States in the 2021 to 2022 academic year, 113 (85.6%) were men and 19 (14.4%) were women (P < .001). Within the past 5 years, 419 fellows were listed as completing a sports medicine fellowship, with 375 (89.5%) being men, and 44 (10.5%) being women (P < .001). There was no significant difference in the gender composition of current fellows compared with the composition of fellows within the last 5 years (P = .74). When we examined gender trends in sports medicine faculty, 639 (86.6%) were men and 99 (13.4%) were women (P < .001). There were 14 women (14.4%) orthopaedic sports medicine faculty in leadership positions (i.e., program director or assistant program director) compared with 83 men in such positions (85.6%) (P < .001). Conclusions: Orthopaedic sports medicine fellowships remain heavily male-dominated on all levels, including fellows, faculty, and leadership. There were no differences in the gender composition of current fellows when compared with those who graduated in the last 5 years, suggesting persistent gender disparity and the need for novel initiatives to enhance gender diversity in sports medicine. Level of Evidence: IV, descriptive study.

16-Hydroxy-ent-halima-5(10),13-dien-15,16-olide from Polyalthia longifolia targets adipogenesis by inhibiting mitotic clonal expansion and ameliorates dyslipidemia.

Obesity-related metabolic disorders are increasing at an alarming rate worldwide. The FDA has approved many molecules for weight loss therapy; most of them act on the gut level by inhibiting lipid uptake or on the central nervous system by controlling appetite. Limitations and drawbacks have propelled the search for new pharmacophores exhibiting favourable metabolic alteration at adipocytes, and natural products have always been there to prove their worth. In our efforts, we have identified 16-hydroxy-ent-halima-5(10),13-dien-15,16-olide (PLH), a halimane diterpene isolated from Polyalthia longifolia, demonstrating anti-adipogenic and anti-dyslipidemic activity. It inhibited adipogenesis in 3T3-L1 preadipocyte and C3H10T1/2 mesenchymal stem cell lines. Furthermore, it decreased set of adipogenic markers at transcript and protein levels. Cell cycle studies indicated that PLH halts the mitotic clonal expansion. Mechanistic studies shows that PLH activate Wnt/ß-catenin signaling pathway to inhibit the adipogenesis. The study suggested that PLH inhibited adipogenesis during the early phase of differentiation by targeting mitotic clonal expansion and arresting the cell cycle in the G1 phase of the cell cycle. It improved the dyslipidemic condition in HFD-fed hamsters by decreasing the body weight, fat mass, eWAT weight and improving the serum lipid profile. Overall, PLH has been found as a potential drug candidate and a pharmacophore for combating metabolic disorders including obesity and dyslipidemia.

Bullying in Orthopaedic Surgery: A Survey of US Orthopaedic Trainees and Attending Surgeons.

INTRODUCTION: Bullying is a notable problem in surgery, creating a hostile environment for surgeons and trainees, and may negatively affect patient care. However, specific details regarding bullying in orthopaedic surgery are lacking. The primary aim of this study was to determine the prevalence and nature of bullying within orthopaedic surgery in the United States. METHODS: A deidentified survey was developed using the survey created by the Royal College of Australasian Surgeons and the validated Negative Acts Questionnaire-Revised survey tool. This survey was distributed to orthopaedic trainees and attending surgeons in April 2021. RESULTS: Of the 105 survey respondents, 60 (60.6%) were trainees and 39 (39.4%) were attending surgeons. Although 21 respondents (24.7%) stated they had been bullied, 16 victims (28.1%) did not seek to address this behavior. Perpetrators of bullying were most commonly male (49/71, 67.2%) and the victims' superior (36/82, 43.9%). Five bullying victims (8.8%) reported the behavior, despite 46 respondents (92.0%) stating that their institution has a specific policy against bullying. CONCLUSION: Bullying behavior occurs in orthopaedic surgery, with perpetrators being most commonly male and the victims' superiors. Despite the fact that an overwhelming majority of institutions have policies against bullying, the reporting of such behavior is lacking.

WITHDRAWN:Persistent Lack of Female Orthopaedic Sports Medicine Fellows

PURPOSE: The purpose of this study was to evaluate the gender composition of fellows, faculty, and leaders within orthopaedic sports medicine fellowship programs to provide a more complete analysis of gender diversity within this subspecialty. METHODS: Official program websites of orthopaedic sports medicine fellowships listed on the Arthroscopy Association of North America (AANA) fellowship directory were examined. Data collected for analysis included the gender of program directors, fellowship faculty, orthopaedic surgery department faculty, current sports medicine fellows, and fellows who graduated within the last five years. RESULTS: Of the 132 orthopaedic sports medicine fellows in training in the United States in the 2021-2022 academic year, 113 (85.6%) were men and 19 (14.4%) were women (p<0.001). Within the past five years, 419 fellows were listed as completing a sports medicine fellowship, with 375 (89.5%) being men, and 44 (10.5%) being women (p<0.001). There was no significant difference in the gender composition of current fellows compared to the composition of fellows within the last 5 years (p=0.74). When examining gender trends in sports medicine faculty, 639 (86.6%) were men and 99 (13.4%) were women (p<0.001). There were 14 women (14.4%) orthopaedic sports medicine faculty in leadership positions (i.e., program director or assistant program director) compared to 83 men in such positions (85.6%) (p<0.001) CONCLUSIONS: Orthopaedic sports medicine fellowships remain heavily male-dominated on all levels, including fellows, faculty, and leadership. There were no differences in the gender composition of current fellows when compared to those who graduated in the last five years, suggesting persistent gender disparity and the need for novel initiatives to enhance gender diversity in sports medicine.

Case 312: Dercum Disease.

HISTORY: A 29-year-old woman was referred for US of bilateral breasts during evaluation for noncyclical mastalgia predominantly in the left breast of 8 months duration. She had been taking selective serotonin receptor inhibitors for the past 6 months for a clinical diagnosis of generalized anxiety disorder. A detailed medical history revealed breast cancer in the patient's mother and grandmother. There was no history of weight loss or appetite loss, nor was there a history of any altered bowel or bladder habits. The patient was overweight, with a body mass index of 26.8 kg/m2, and appeared anxious during the general physical examination, with an increased pulse (102 beats per minute) and normal blood pressure (118/82 mm Hg). Local examination revealed multiple small mobile painful lesions that were palpable in all quadrants of the bilateral breasts, anterior abdominal wall, and forearm. On further questioning, the patient reported similar painful lesions were present in her mother and one brother. Laboratory investigations showed a normal hemoglobin level (12.4 g/dL; normal range, 12-15 g/dL), a total leukocyte count of 9000 cells per microliter (9 cells × 109/L) (normal range, 4500-11 000 cells per microliter [4.5-11 cells × 109/L]), a normal differential leukocyte count (74% neutrophils [normal range, 40%-80%], 24% lymphocytes [normal range, 20%-40%], and 2% eosinophils [normal range, 1%-4%]), and an erythrocyte sedimentation rate of 5 mm per hour (normal range, 0-29 mm per hour). High-frequency US of bilateral breasts was performed in conjunction with Color Doppler US and shear-wave elastography of representative lesions in the breasts. Similar lesions were also found in the subcutaneous plane of the right forearm and the anterior abdominal wall.

Can Sublingual Nitrate Improve Visualization of Lower Limb Arteries on Computed Tomography Angiography?

OBJECTIVE: The aim of the study is to evaluate the role of sublingual nitrate in improving vessel visualization on peripheral computed tomography angiography (CTA). METHODS: Fifty patients clinically diagnosed with peripheral arterial disease of the lower limb were prospectively included in this study: Twenty-five underwent CTA after sublingual nitrate administration (nitrate group) and 25 without (non-nitrate group). Two blinded observers qualitatively and quantitatively assessed the data thus generated. The mean luminal diameter, intraluminal attenuation, site, and percentage of stenosis were evaluated in all segments. Assessment of collateral visualization at sites of significant stenosis was also done. RESULTS: Patients in the nitrate and non-nitrate groups were similar in age and sex characteristics ( P > 0.05).On subjective evaluation, there was significantly improved visualization of the femoropopliteal and tibioperoneal vasculature of the lower limb in the nitrate group compared with the non-nitrate group ( P < 0.05). Quantitative evaluation showed a statistically significant difference in the measured arterial diameters for all evaluated segments in the nitrate group versus the non-nitrate group ( P < 0.05). Intra-arterial attenuation was significantly greater for all segments in the nitrate group resulting in better contrast opacification in these studies. Collateral visualization around segments with more than 50% stenosis/occlusion was also better in the nitrate group. CONCLUSIONS: Our study suggests that nitrate administration before peripheral vascular CTA can improve visualization, especially in the distal segments by increasing the vessel diameter and intraluminal attenuation along with better delineation of the collateral circulation around stenotic areas. It may also improve the number of evaluable segments of vasculature in these angiographic studies.

Anterior lumbar spinal fusion surgery associated with lower risk of stroke, pneumonia, and infection compared to posterior lumbar spinal fusion surgery.

Background: Prior studies, comparing anterior and posterior approaches to lumbar fusion surgery, found similar fusion rates and clinical outcomes, but are limited by sample size. Further evaluation of the postoperative complications of each approach is necessary. Methods: The MSpine database by PearlDiver was queried using ICD-9, ICD-10, and CPT codes to identify patients who had undergone single-level anterior or posterior lumbar interbody fusion surgery. Readmission rates, ileus, lower extremity DVT, infection, pneumonia, and stroke were used to compare post-operative complications of an anterior vs. posterior approach. Results: 112,023 patients were included in this study, with 38,529 (34.4%) in the anterior group (ALIF/LLIF) and 73,494 (65.6%) in the posterior group (PLIF/TLIF). At both 30 and 90-days postoperative, patients undergoing an anterior approach to lumbar interbody fusion had a higher odds ratio of lower extremity DVT (30-day OR: 1.19, 90-day OR: 1.16; P<0.05) and ileus complication (30-day OR: 1.87, P= <.05; 90-day OR: 1.81, P<.05). At both 30 and 90-days postoperative, patients undergoing a posterior approach had a higher odds ratio of stroke (30-day: OR: 0.79, 90-day OR: 0.87; P<0.05), transfusion (30-day OR: 0.66, 90-day OR: 0.69; P<.05), infection (30-day OR: 0.88, 90-day OR: 0.91; P <.05), and pneumonia (30-day OR: 0.85, 90-day OR: 0.90; P<.05). There was no statistically significant difference in myocardial infarction or pulmonary embolism between both approaches at 30 and 90-days postoperative. Conclusions: Anterior and posterior approaches for lumbar interbody fusion were associated with differences in postoperative complications at 30 and 90-days. The complication profiles associated with each approach can inform surgeon treatment decisions based on patient profiles.

Patients Report A Positive Experience on Social Media After Bankart Repair.

Purpose: The purpose of this cross-sectional study was to analyze publicly available posts on Instagram and Twitter to gain an understanding of patients' perspectives regarding Bankart injuries and repair. Methods: Public posts on Instagram and Twitter were queried from June 1, 2019, to June 1, 2020, with the following hashtags: #Bankart #Bankartrepair #Bankartlesion #labrumrepair #labralrepair #shoulderdislocation. Posts that did not contain those hashtags were excluded. In addition, posts that included that hashtag but displayed content unrelated to Bankart repair were excluded. A binary categorical system was used for media format (picture or video), perspective (patient, family or friend, physician, hospital or physical therapy group, professional organization, news media, or industry), timing (preoperative, postoperative, nonoperative), tone (positive, negative, or neutral), content (surgical site, hospital or surgeon, imaging, rehabilitation, activities of daily living [ADLs], return to work, surgical instruments, or education), post popularity (number of likes), and geographic location. Results: 1,154 Instagram posts were identified. 722/1,154 posts (62.6%) were made by patients. 600 (52.0%) of the post tones were positive, 407 (35.3%) were neutral, and 667 (57.8%) were postoperative. The most common content included in Instagram posts were ADLs (577; 50.0%), education (233; 20.2%), and rehabilitation (226; 19.6%). Overall, posts had an average of 117 likes and had geotags from 49 different countries. 155 tweets were identified, 92 of which (59.4%) were made by physicians, 113 (72.9%) were neutral, 127 (81.9%) were nonoperative, and the most common type of content posted was education (130; 83.9%). Overall, posts on Twitter had an average of 3.2 likes and had geotags from 4 different countries. Conclusions: Instagram posts were made mostly by patients postoperatively and focused on ADLs. The tone of the Instagram posts indicates that a majority of patients have a positive experience with Bankart repair. The majority of tweets were made by physicians and provided educational information with a neutral tone. Clinical Relevance: Exploring patient's experiences with Bankart repair on social media provides insight into their overall experience with the surgery. The majority of patients reported a positive experience.

Sodium butyrate reduces endoplasmic reticulum stress by modulating CHOP and empowers favorable anti-inflammatory adipose tissue immune-metabolism in HFD fed mice model of obesity.

Over the past decade, the gut microbiome has been linked to several diseases including gastrointestinal diseases, cancer, immune disorder and metabolic syndrome. Shifts in the gut bacterial population affect the overall metabolic health status leading towards obesity and Type II diabetes mellitus. Secondary metabolites secreted by the gut microbiome interact with various host-sensing signalling pathways and are responsible for functional modulation of immune resident cells in metabolic tissues (Blüher, 2019). Of these, short- chain fatty acids (SCFAs) i.e., acetate, propionate and butyrate have been significantly correlated with the disposition of diabetes and metabolic disorder. The altered gut microbial population depletes the intestinal barrier causing entry of LPS into circulation and towards metabolic tissues triggering pro-inflammatory responses. As butyrate has been known to maintain intestinal integrity, we aimed to assess the apparent effect of externally given sodium butyrate [NaB] on immuno-metabolic profiling of adipose tissue, and its association with metabolic and inflammatory status of adipose tissue. To assess this, we put groups of C57BL/6 mice i.e., Control fed with a regular chow diet and another group that was fed on a high fat diet (HFD, 60%) for 8 weeks. Following this, the HFD group were further subdivided into two groups one fed with HFD and the other with HFD + NaB (5%w/w) for another 8 weeks. Body composition, weight gain, body adiposity and biochemical parameters were assessed. NaB fed group showed an improved metabolic profile compared to HFD fed group. Administration of NaB also improved glucose tolerance capacity and insulin sensitivity as determined by IPGTT and ITT profiles. Earlier reports have shown gut leakage and increased LPS in circulation is the primary cause of setting up inflammation at the tissue level. Our studies exhibited that, NaB increased the expression of tight junction proteins of intestinal linings and thereby enhanced intestinal barrier integrity. The FITC dextran permeability assay further confirmed this enhanced intestinal barrier integrity. We assessed the quantitative and relative population of different types of resident immune cells from a stromal vascular fraction of adipose tissue. Flow cytometry studies revealed significantly increased M2 (CD206+ ) macrophages and Tregs (CD25+ ) relative to the M1 macrophage population and CD4+ T cells respectively in NaB treated mice, suggesting its potential role in alleviating the inflammatory profile. In a nutshell, taken together better glucose tolerance, better gut health, reduced inflammatory adipose tissue immune cells, suggest potential beneficial role of sodium butyrate in alleviating overall inflammation and metabolic dysfunction associated with obesity.

Examining the Relationship Between Mild Traumatic Brain Injuries and Development of Mental Illness Disorders in a Mid-Term Follow-up Period.

OBJECTIVE: The sequalae of mild concussions continue to emerge with increased awareness in sports-related injuries. This study aimed to quantify the number of patients who are affected by a mental illness within 3 yrs of a concussion and identify whether demographic differences exist that may influence a mental illness diagnosis. DESIGN: Using a nationwide database, data were queried for a diagnosis of concussion, capturing patients aged 18-45 yrs with no previous mental illness, and then identified if these patients were diagnosed with a mental illness within 3 yrs of their concussion. The mental illnesses specifically chosen for this study included depression, anxiety, panic disorder, posttraumatic stress disorder, bipolar, and schizophrenia. RESULTS: Within 3 yrs after a concussion, 48% of patients were later diagnosed with a mental illness. All of the mental illnesses this study chose to evaluate were present in a higher proportion of patients after a concussion than the general population. CONCLUSIONS: The mechanism between concussions and mental illness remains unclear. A large proportion of patients who experience a concussion are later diagnosed with a mental illness within 3 yrs. Patients with a history of a previous concussion may benefit from screening for the development of a mental illness.

Galectin-3 S-glutathionylation regulates its effect on adipocyte insulin signaling.

Protein-S-glutathionylation promotes redox signaling in physiological and oxidative distress conditions. Galectin-3 (Gal-3) promotes insulin resistance by down-regulating adipocyte insulin signaling, however, its S-glutathionylation and significance is not known. In this context, we report reversible S-glutathionylation of Gal-3. Site-directed mutagenesis established Gal-3 Cys187 as the putative S-glutathionylation site. Glutathionylated Gal-3 prevents Gal-3(WT)-Insulin Receptor interaction and facilitates insulin-induced murine adipocyte p-IRS1(tyr895) and p-AKT(ser473) signaling and glucose uptake in a Gal-3 Cys187 glutathionylation dependent manner in murine adipocytes, as assessed by Western blotting and 2-NBDG uptake assay respectively. Pre-glutathionylated Gal-3 at Cys187 resisted irreversible oxidation by H2O2. M2 macrophages showed enhanced Gal-3 S-glutathionylation when compared to M1 phenotype. Serum and stromal vascular fraction (SVF) isolated from control mice showed increased Gal-3 S-glutathionylation as compared to db/db mice. A significant increase in Gal-3 S-glutathionylation was observed in metformin-treated db/db mice when compared to db/db mice alone. Similar to murine, enhanced Gal-3 S-glutathionylation is observed in primary human monocyte derived M2 macrophages when compared to the M1 macrophage phenotype and Gal-3 regulates primary human adipocyte insulin signaling in a glutathionylation dependent manner. Collectively, we identified Gal-3 S-glutathionylation as a protective phenomenon, which relieves its inhibitory effect on adipocyte insulin signaling.

Case 312.

HISTORY: A 29-year-old woman was referred for US of bilateral breasts during evaluation for noncyclical mastalgia predominantly in the left breast of 8 months duration. She had been taking selective serotonin receptor inhibitors for the past 6 months for a clinical diagnosis of generalized anxiety disorder. A detailed medical history revealed breast cancer in the patient's mother and grandmother. There was no history of weight loss or appetite loss, nor was there a history of any altered bowel or bladder habits. The patient was overweight, with a body mass index of 26.8 kg/m2, and appeared anxious during the general physical examination, with an increased pulse (102 beats per minute) and normal blood pressure (118/82 mm Hg). Local examination revealed multiple small mobile painful lesions that were palpable in all quadrants of the bilateral breasts, anterior abdominal wall, and forearm. On further questioning, the patient reported similar painful lesions were present in her mother and one brother. Laboratory investigations showed a normal hemoglobin level (12.4 g/dL; normal range, 12-15 g/dL), a total leukocyte count of 9000 cells per microliter (9 cells × 109/L) (normal range, 4500-11 000 cells per microliter [4.5-11 cells × 109/L]), a normal differential leukocyte count (74% neutrophils [normal range, 40%-80%], 24% lymphocytes [normal range, 20%-40%], and 2% eosinophils [normal range, 1%-4%]), and an erythrocyte sedimentation rate of 5 mm per hour (normal range, 0-29 mm per hour). High-frequency US of bilateral breasts (Figs 1, 2) was performed in conjunction with Color Doppler US (Fig 3) and shear-wave elastography of representative lesions in the breasts (Fig 4). Similar lesions were also found in the subcutaneous plane of the right forearm (Fig 5) and the anterior abdominal wall (Fig 6).

Coelogin ameliorates metabolic dyshomeostasis by regulating adipogenesis and enhancing energy expenditure in adipose tissue.

Obesity and associated metabolic disorders are heading up with an alarming rate in developing nations. One of highly sought solution for metabolic disorders is to identify natural molecule with an ability to reduce obesity and increase insulin sensitivity. Coelogin (CLN) is a phenanthrene derivative isolated from the ethanolic extract of Coelogyne cristata. In our constant efforts to identify novel anti-dyslipidemic and anti-adipogenic compounds using CFPMA (common feature pharmacophore model using known anti-adipogenic compounds) model, predicted possible anti-adipogenic activity of CLN. In vitro results showed significant inhibition of adipogenesis in 3T3-L1 and C3H10T1/2 cell by CLN. It arrests the cell cycle in G1 phase of interphase and inhibits mitotic clonal expansion to regulate adipogenesis. CLN elicits insulin sensitizing effect in mature adipocytes. During extracellular flux assessment studies, it increases oxidative respiration and energy expenditure in adipocytes. In vivo, CLN reversed HFD-induced dyslipidemia as well as insulin resistance in C57BL/6 mice. It promoted the expression of genes involved in improved mitochondrial function and fatty acid oxidation in eWAT. CLN restored energy expenditure and increased the capacity of energy utilization in HFD fed mice. Taken together, the study indicated beneficial effects of CLN in combating obesity-associated metabolic complications.

lncRNADetector: a bioinformatics pipeline for long non-coding RNA identification and MAPslnc: a repository of medicinal and aromatic plant lncRNAs.

Long non-coding RNAs (lncRNAs) are an emerging class of non-coding RNAs and potent regulatory elements in the living cells. High throughput RNA sequencing analyses have generated a tremendous amount of transcript sequence data. A large proportion of these transcript sequences does not code for proteins and are known as non-coding RNAs. Among them, lncRNAs are a unique class of transcripts longer than 200 nucleotides with diverse biological functions and regulatory mechanisms. Recent emerging studies and next-generation sequencing technologies show a substantial amount of lncRNAs within the plant genome, which are yet to be identified. The computational identification of lncRNAs from these transcripts is a challenging task due to the involvement of a series of filtering steps. We have developed lncRNADetector, a bioinformatics pipeline for the identification of novel lncRNAs, especially from medicinal and aromatic plant (MAP) species. The lncRNADetector has been utilized to analyse and identify more than 88,459 lncRNAs from 21 species of MAPs. To provide a knowledge resource for the plant research community towards elucidating the diversity of biological roles of lncRNAs, the information generated about MAP lncRNAs (post-filtering steps) through lncRNADetector has been stored and organized in MAPslnc database (MAPslnc, https://lncrnapipe.cimap.res.in). The lncRNADetector web server and MAPslnc database have been developed in order to facilitate researchers for accurate identification of lncRNAs from the next-generation sequencing data of different organisms for downstream studies. To the best of our knowledge no such MAPslnc database is available till date.

In Silico Identification of miRNA and Targets from Chrysopogon zizanioides (L.) Roberty with Functional Validation from Leaf and Root Tissues.

microRNAs are small non-coding RNA molecule that plays an important role in metabolism. Chrysopogon zizanioides (L.) Roberty is an important aromatic plant used in perfumery industries, soil, water conservation, and agricultural practices. In this study, the transcriptomic sequence of vetiver leaf and root was subjected to miRNA identification by the computational methods. miRNA identification was carried out using a homology-based method by C-mii software with several other online tools. A total of 80 miRNA were identified from both leaf and root sequences. Target identification was done by identified miRNA sets. A total of 25 and 31 miRNA families were identified in both leaf and root, respectively, with ten common families involve in different ontological function. miR169 and miR5021 regulate most of the target in leaf and root. In vetiver, many primary and secondary metabolism elements are regulated by miRNA as photo-system, transcription factor, terpenoid metabolism, etc. Here is the first in silico study revealing the specific miRNAs and their target genes for corresponding root and leaf tissues respectively in C. zizanioides.

Role of brown adipose tissue in modulating adipose tissue inflammation and insulin resistance in high-fat diet fed mice.

Obesity results in the chronic activation of innate immune system and subsequently sets in diabetes. Aim of the study was to investigate the immunometabolic role of brown adipose tissue (BAT) in the obesity. We performed both BAT transplantation as well as extirpation experiments in the mouse model of high-fat diet (HFD)-induced obesity. We carried out immune cell profiling in the stromal vascular fraction (SVF) isolated from epididymal white adipose tissue (eWAT). BAT transplantation reversed HFD-induced increase in body weight gain and insulin resistance without altering diet intake. Importantly, BAT transplantation attenuated the obesity-associated adipose tissue inflammation in terms of decreased pro-inflammatory M1-macrophages, cytotoxic CD8a T-cells and restored anti-inflammatory regulatory T-cells (Tregs) in the eWAT. BAT transplantation also improved endogenous BAT activity by elevating protein expression of browning markers (UCP-1, PRDM16 and PGC1α) in it. In addition, BAT transplantation promoted the eWAT expression of various genes involved in fatty acid oxidation (such as Elvol3 and Tfam,). In contrast, extirpation of the interscapular BAT exacerbated HFD-induced obesity, insulin resistance and adipose tissue inflammation (by increasing M1 macrophages, CD8a T-cell and decreasing Tregs in eWAT). Taken together, our results suggested an important role of BAT in combating obesity-associated metabolic complications. These results open a novel therapeutic option to target obesity and related metabolic disorders like type 2 diabetes.