Venture Capital's Role in Advancing Plastic Surgery.

Plastic surgery sector has experienced significant growth, driven by an aging population's demand for minimally invasive procedures and technological innovation. Despite this, the role of venture capital (VC) in driving innovation within this sector remains underexplored. This study aimed to analyze the trends in VC investments in plastic surgery over the last 20 years, providing insights into the financial landscape of the sector. A retrospective cross-sectional analysis was conducted on VC investments in plastic and aesthetic surgery companies worldwide from January 1, 2003 to December 31, 2023, utilizing PitchBook (Seattle, WA). Companies were categorized into therapeutic and thematic areas, with investment trends analyzed by deal and company values, average investment size, and total capital invested. The study found 543 VC firms made 402 investments in 163 companies, totaling $1.98 billion, increasing by 15,143% over the study period, and focused on general plastic surgery and facial cosmetic procedures. Significant investments were also made in surgical software (25.3%), biotechnology and drug discovery (22.8%), and clinic and outpatient services (20.3%). Geographically, most investments were made in companies registered in Asia (45%) and North America (33.2%). VC investments have contributed to the growth and innovation in the plastic surgery sector, particularly in minimally invasive devices. The focus on general and facial cosmetic surgery aligns with market demand trends for aesthetic procedures. These findings underscore the importance of VC in shaping the future of plastic surgery and suggest the potential for strategic investments to further drive innovation.

Phytochemistry and Polypharmacological Potential of Colebrookea oppositifolia Smith.

BACKGROUND: Colebrookea oppositifolia Smith. is a valuable traditional therapeutic plant belonging to the family Lamiaceae. It is a dense and wool-like shrub that is mostly found in subtropical regions of some countries of Asia, such as China and India. It has been widely used for the mitigation of nervous system disorders like epilepsy. The active constituents of the plant have exhibited antioxidant, anti-microbial, and antifungal properties, which are considered due to the presence of polyphenols and flavonoids as chief chemical constituents. Flavonoids like quercetin, landenein, chrysin, and 5, 6, 7-trimethoxy flavones cause protein denaturation of the microbial cell wall. OBJECTIVES: To comprehend and assemble the fragmented pieces of evidence presented on the traditional uses, botany, phytochemistry, and pharmacology of the plant to reconnoiter its therapeutic perspective and forthcoming research opportunities. METHODS: The available information on Colebrookea oppositifolia has been established by electronically searching peer-reviewed literature from PubMed, Google Scholar, Springer, Scopus, Web of Science, and Science Direct over the earlier few years. RESULTS: The plant has been greatly used for the preparation of many herbal medicines which are used for treating traumatic injuries, fever, rheumatoid arthritis, headache, and gastric problems. From the aerial parts of the plant, a phenylethanoid glycoside named acteoside has been isolated and evaluated for its therapeutic potential viz. immunomodulatory, neuroprotective, hepatoprotective, analgesic, anti-tumour, antispasmodic, antioxidant, antibacterial, free radical scavenger, and improving sexual function. Acteoside showed neuroprotective activities against Aß-peptide, which is neurotoxic and causes apoptosis. The petroleum ether extract of the plant leaves offers many active compounds like sitosterol, n-triacontane, hydroxydotriacontyl ferulate, acetyl alcohol, and 3,7,4,2-tetramethoxyflavones which have shown hepatoprotective potential. CONCLUSION: The plant should be evaluated further for the estimation of some other health benefits. The consequences of restricted pharmacological screening and reported phytomolecules of Colebrookea oppositifolia Smith. advocate that there is still an exigent requisite for in-depth pharmacological studies of the plant.

GTS-21, a selective alpha7 nicotinic acetylcholine receptor agonist, ameliorates diabetic nephropathy in Leprdb/db mice.

Diabetic nephropathy (DN) is a serious complicating factor in human type 2 diabetes mellitus (T2DM), and it commonly results in end-stage renal disease (ESRD) that requires kidney dialysis. Here, we report that the α7 nicotinic acetylcholine receptor (α7nAChR) agonist GTS-21 exerts a novel anti-inflammatory action to ameliorate DN, as studied using an inbred strain of Leprdb/db mice in which hyperglycemia and obesity co-exist owing to defective leptin receptor (Lepr) signaling. For this analysis, GTS-21 was administered to 10-12 week-old male and female mice as a 4 mg/kg intraperitoneal injection, twice-a-day, for 8 weeks. Kidney function and injury owing to DN were monitored by determination of plasma levels of BUN, creatinine, KIM-1 and NGAL. Histologic analysis of glomerular hypertrophy and mesangial matrix expansion were also used to assess DN in these mice. Concurrently, renal inflammation was assessed by measuring IL-6 and HMGB1, while also quantifying renal cell apoptosis, and apoptotic signaling pathways. We found that Leprdb/db mice exhibited increased markers of BUN, creatinine, NGAL, KIM-1, IL-6, cytochrome C, and HMGB-1. These abnormalities were also accompanied by histologic kidney injury (mesangial matrix expansion and apoptosis). Remarkably, all such pathologies were significantly reduced by GTS-21. Collectively, our results provide new evidence that the α7nAChR agonist GTS-21 has the ability to attenuate diabetes-induced kidney injury. Additional studies are warranted to further investigate the involvement of the vagal cholinergic anti-inflammatory reflex pathway (CAP) in ameliorating diabetic nephropathy.

Comment on Kim et al. The Association between Coffee Consumption and Risk of Colorectal Cancer in a Korean Population. Nutrients 2021, 13, 2753.

We read with interest the recent publication in Nutrients by Kim et al. [...].

Pharmacological and genetic perturbation establish SIRT5 as a promising target in breast cancer.

SIRT5 is a member of the sirtuin family of NAD+-dependent protein lysine deacylases implicated in a variety of physiological processes. SIRT5 removes negatively charged malonyl, succinyl, and glutaryl groups from lysine residues and thereby regulates multiple enzymes involved in cellular metabolism and other biological processes. SIRT5 is overexpressed in human breast cancers and other malignancies, but little is known about the therapeutic potential of SIRT5 inhibition for treating cancer. Here we report that genetic SIRT5 disruption in breast cancer cell lines and mouse models caused increased succinylation of IDH2 and other metabolic enzymes, increased oxidative stress, and impaired transformation and tumorigenesis. We, therefore, developed potent, selective, and cell-permeable small-molecule SIRT5 inhibitors. SIRT5 inhibition suppressed the transformed properties of cultured breast cancer cells and significantly reduced mammary tumor growth in vivo, in both genetically engineered and xenotransplant mouse models. Considering that Sirt5 knockout mice are generally normal, with only mild phenotypes observed, these data establish SIRT5 as a promising target for treating breast cancer. The new SIRT5 inhibitors provide useful probes for future investigations of SIRT5 and an avenue for targeting SIRT5 as a therapeutic strategy.

Potential role of EphrinA2 receptors in postconditioning induced cardioprotection in rats.

EphA2 receptor has emerged as a novel cardioprotective target against myocardial infarction by preserving cardiac function, limiting infarct size and inflammation and enhancing cell survival via elevating phosphorylated Akt protein levels. However, the role of Eph receptors in postconditioning remains to be elucidated. Thus, the present study was designed to explore the role of EphA2 receptors in cardioprotective mechanism of postconditioning by employing Doxazosin as EphA2 receptor agonist, Lithocholic acid as antagonist and Wortmannin as specific phosphoinositide 3-kinase (PI3K) inhibitor. In Langendorff perfused isolated rat hearts, exposure of ischemia for 30 min succeeded by reperfusion for 2 h produced cardiac damage as determined by increase in size of infarct, LVDP, liberation of LDH and CK in effluent from coronary arteries. The reperfused hearts were homogenized and tissue concentrations of TBARs, reduced GSH and Catalase were determined. A marked rise in infarct size, liberation of LDH and CK in effluent and TBARs in myocardial tissue was observed in ischemic and reperfused hearts. Ischemic postconditioning comprising of 6 alternate episodes of 10 s ischemia and 10 s reperfusion and pharmacological post-conditioning by Doxazosin infusion for 5 min Before reperfusion confers significant protection against myocardial injury as manifested by remarkably decreased infarct size, levels of LDH, CK and tissue TBARs along with increase in GSH and Catalase activity. Pre-treatment of EphA2 antagonist, Lithocholic acid and PI3K inhibitor, Wortmannin attenuated the cardioprotective effect of postconditioning. Our results suggest that EphA2 receptors may be involved in postconditioning mediated cardioprotection probably through PI3K/Akt pathway.

Surgical treatment of early-onset idiopathic scoliosis in the United States: a trend analysis of 15 years (1997-2012).

BACKGROUND CONTEXT: Early-onset scoliosis is a challenging problem that is defined as a curvature of the spine of more than 10 degrees identified in a child less than 10 years. Early-onset idiopathic scoliosis (EOIS) can cause substantial morbidity and may require surgical intervention. PURPOSE: The aim of the present study was to identify the trends of EOIS type of surgeries, length of hospital stay, in-hospital complications, and total inpatient admission charges over a 15-year study period in the United States from 1997 to 2012. STUDY DESIGN/SETTING: This retrospective study used the ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) codes from the Healthcare Cost and Utilization Project (HCUP) Kids Inpatient's Database (KID) for a 15-year period (1997-2012). PATIENT SAMPLE: We identified a total of 897 patients with EOIS over the 15-year study period. OUTCOME MEASURES: The present study determines the current trends for EOIS surgeries. METHODS: The present study had no funding sources or any potential conflicts of interest associated biases. Idiopathic scoliosis patients with ages between 0 and <10 years were identified from the Kids' Inpatient Database with ICD-9-CM code 737.30. Posterior, anterior, and combined spinal surgeries were identified in EOIS through the procedure codes. Patients' gender, discharge diagnosis (comorbidities), hospital length of stay (LOS), mortality rates, hospital charges, and in-hospital complication rate data were collected between 1997 and 2012. The primary grouping variable of the study was the type of surgery (posterior, anterior, and combined). The trends of each variable (female gender, mortality rates, in-hospital complications rates, discharge diagnosis, LOS, and total hospital charges) were assessed for each surgical group separately. Cost inflation of hospital charges was adjusted for the year 2012. An analysis of variance test was used to analyze continuous variables and a chi-square test was used for categorical variables. A linear regression test was used to assess the trend of changes. p≤.05 was considered statistically significant. RESULTS: The study identified 897 patients, with 546 (61%) of them requiring surgery. Spine deformity surgery rates significantly decreased in patients with EOIS over time from 75% in 1997 to 47% in 2012, p=.019. In the surgery cohort, the male to female distribution was 37% and 63%, respectively. The overall mortality rate was 0.1%. The average length of hospital stay was 8 days and the average number of discharge diagnosis was 5.3. Aggregated complications were seen in 6% of the patients. The total mean hospital charge (per 2012 US dollars) was $119,613, which increased significantly for all types of surgeries. Over the 15-year study period, 62% (n=342) of the patients had posterior surgeries, 13% (n=71) of the patients had anterior surgeries, and 24% (n=133) of the patients had combined (anterior and posterior) surgeries. Posterior surgeries increased significantly from 33% in 1997 to 91% in 2012 (p<.004). Combined surgeries saw a significant decline from 50% to 4.3% (0<0.001). Anterior surgeries also decreased from 17% to 4.3% (p<.126), but this did not reach statistical significance. CONCLUSIONS: From 1997 to 2012 (15 years) study period of patients with EOIS, posterior-based surgeries significantly increased. The overall surgery rate has significantly decreased for these patients. A significant increase in hospital charges were noticed in posterior, anterior, and combined surgeries.

Animal models of acute renal failure.

The animal models are pivotal for understanding the characteristics of acute renal failure (ARF) and development of effective therapy for its optimal management. Since the etiology for induction of renal failure is multifold, therefore, a large number of animal models have been developed to mimic the clinical conditions of renal failure. Glycerol-induced renal failure closely mimics the rhabdomyolysis; ischemia-reperfusion-induced ARF simulate the hemodynamic changes-induced changes in renal functioning; drug-induced such as gentamicin, cisplatin, NSAID, ifosfamide-induced ARF mimics the renal failure due to clinical administration of respective drugs; uranium, potassium dichromate-induced ARF mimics the occupational hazard; S-(1,2-dichlorovinyl)-L-cysteine-induced ARF simulate contaminated water-induced renal dysfunction; sepsis-induced ARF mimics the infection-induced renal failure and radiocontrast-induced ARF mimics renal failure in patients during use of radiocontrast media at the time of cardiac catheterization. Since each animal model has been created with specific methodology, therefore, it is essential to describe the model in detail and consequently interpret the results in the context of a specific model.

Adaptogenic potential of curcumin in experimental chronic stress and chronic unpredictable stress-induced memory deficits and alterations in functional homeostasis.

The present study was designed to investigate the role of curcumin in chronic stress and chronic unpredictable stress-induced memory deficits and alteration of functional homeostasis in mice. Chronic stress was induced by immobilizing the animal for 2 h daily for 10 days, whereas chronic unpredictable stress was induced by employing a battery of stressors of variable magnitude and time for 10 days. Curcumin was administered to drug-treated mice prior to induction of stress. Body weight, adrenal gland weight, ulcer index and biochemical levels of glucose, creatine kinase, cholesterol, corticosterone, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) were evaluated to assess stress-induced functional changes. Memory deficits were evaluated using the elevated plus maze (EPM) model. Chronic stress and chronic unpredictable stress significantly increased the levels of corticosterone, glucose and creatine kinase and decreased cholesterol levels. Moreover, chronic stress and chronic unpredictable stress resulted in severe memory deficits along with adrenal hypertrophy, weight loss and gastric ulceration. Chronic stress and chronic unpredictable stress also increased oxidative stress assessed in terms of increase in TBARS and decrease in GSH levels. Pretreatment with curcumin (25 and 50 mg/kg p.o.) attenuated chronic stress and chronic unpredictable stress-associated memory deficits, biochemical alterations, pathological outcomes and oxidative stress. It may be concluded that curcumin-mediated antioxidant actions and decrease in corticosterone secretion are responsible for its adaptogenic and memory restorative actions in chronic and chronic unpredictable stress.