α-Lipoic acid chemistry: the past 70 years.

α-Lipoic acid (ALA) is a naturally occurring sulfur-containing fatty acid with high antioxidant activity. It is also used to treat diabetes, nerve pain, weight loss, heart disease, and primary mitochondrial disorders. Moreover, numerous therapeutic agents have been studied for managing other clinical conditions, including for anticancer, anti-HIV, anti-inflammatory, and anti-AD treatments. The medicinal importance of ALA, especially its biologically active form (R-ALA), has attracted considerable attention from synthetic chemists in industrial and academic fields. In this review, we discuss synthetic approaches to ALA and R-ALA over the past 70 years (1952 to the present), which will help medicinal chemists further develop novel routes for their synthesis.

Oxidative stress bridges the gut microbiota and the occurrence of frailty syndrome.

The incidence of frailty gradually increases with age. This condition places a heavy burden on modern society, of which the aging population is increasing. Frailty is one of the most complicated clinical syndromes; thus, it is difficult to uncover its underlying mechanisms. Oxidative stress (OS) is involved in frailty in multiple ways. The association between the gut microbiota (GM) and frailty was recently reported. Herein, we propose that OS is involved in the association between the GM and the occurrence of frailty syndrome. An imbalance between oxidation and antioxidants can eventually lead to frailty, and the GM probably participates in this process through the production of reactive oxygen species. On the other hand, OS can disturb the GM. Such dysbiosis consequently induces or exacerbates tissue damage, leading to the occurrence of frailty syndrome. Finally, we discuss the possibility of improving frailty by intervening in the vicious cycle between the imbalance of OS and dysbiosis.

A Novel Trimethylamine Oxide-Induced Model Implicates Gut Microbiota-Related Mechanisms in Frailty.

Frailty is a complicated syndrome that occurs at various ages, with highest incidence in aged populations, suggesting associations between the pathogenesis of frailty and age-related changes. Gut microbiota (GM) diversity and abundance change with age, accompanied by increased levels of trimethylamine oxide (TMAO), a systemic inflammation-inducing GM metabolite. Thus, we hypothesized that TMAO may be involved in the development of frailty. We successfully established and verified a novel model of frailty in adult mice based on a 4-week intraperitoneal injection regime of TMAO followed by LPS challenge. The frailty index significantly increased in TMAO-treated mice after LPS challenge. TMAO also decreased claudin-1 immunofluorescent staining intensity in the jejunum, ileum, and colon, indicating that the destruction of intestinal wall integrity may increase vulnerability to exogenous pathogens and invoke frailty. 16S sequencing showed that TMAO significantly reduced the GM Firmicutes/Bacteroidetes (F/B) ratio, but not α-diversity. Interestingly, after LPS challenge, more genera of bacterial taxa were differently altered in the control mice than in the TMAO-treated mice. We infer that a variety of GM participate in the maintenance of homeostasis, whereas TMAO could blunt the GM and impair the ability to recover from pathogens, which may explain the continuous increase in the frailty index in TMAO-treated mice after LPS challenge. TMAO also significantly increased serum imidazole metabolites, and led to different patterns of change in serum peptide and phenylpropanoid metabolites after LPS stimulation. These changes indicate that glucose metabolism may be one mechanism by which GM inactivation causes frailty. In conclusion, TMAO leads to frailty by destroying intestinal barrier integrity and blunting the GM response.

[Screening of differentially expressed genes for colorectal cancer and prediction of potential traditional Chinese medicine: based on bioinformatics].

This study screened and analyzed the differentially expressed genes(DEGs) between colorectal cancer(CRC) tissues and normal tissues with bioinformatics techniques to predict biomarkers and Chinese medicinals for the diagnosis and treatment of CRC. The microarray data sets GSE21815, GSE106582, and GSE41657 were downloaded from the Gene Expression Omnibus(GEO), and the DEGs were screened by GEO2 R, followed by the Gene Ontology(GO) tern enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the DEGs based on DAVID. The protein-protein interaction network was constructed by STRING, and MCODE and Cytohubba plug-ins were used to screen the significant modules and hub genes in the network. UCSC, cBioPortal, and Oncomine were employed for hierarchical clustering, survival analysis, Oncomine analysis, and correlation analysis of clinical data. Coremine Medical was applied to predict the Chinese medicinals acting on hub genes. A total of 284 DEGs were screened out, with 146 up-regulated and 138 down-regulated. The up-regulated genes were mainly involved in cell cycle, NLRs pathway, and TNF signaling pathway, and the down-regulated genes were related to mineral absorption, nitrogen metabolism, and bicarbonate reabsorption in proximal tubules. The 15 hub genes were CDK1, CDC20, AURKA, MELK, TOP2 A, PTTG1, BUB1, CDCA5, CDC45, TPX2, NEK2, CEP55, CENPN, TRIP13, and GINS2, among which CDK1 and CDC20 were regarded as core genes. The high expression of CDK1 and CDC20 suggested poor prognosis, and they significantly expressed in many cancers, especially breast cancer, lung cancer, and CRC. The expression of CDK1 and CDC20 was correlated with gender, tumor type, TNM stage, and KRAS gene mutation. The potential effective medicinals against CRC were Scutellariae Radix, Scutellariae Barbatae Herba, Arnebiae Radix, etc. The significant expression of CDK1 and CDC20 can help distinguish tumor tissues from normal tissues, and is related to survival prognosis. Thus, the two can be used as biomarkers for the diagnosis and treatment of CRC. This study provides a reference for related drug development.

Gut microbiota alterations and health status in aging adults: From correlation to causation.

The deterioration of tissue structure and decline in physiological function during aging are accompanied by alterations to the gut microbiota. The elderly has higher risks of various diseases and chronic diseases. However, inter-individual differences are more apparent in elderly than younger, and a proportion of individuals have a delayed onset or even avoid developing chronic diseases. This difference in health status is influenced by both heredity and Lifestyle and environmental factors. During the process of aging, the gut microbiota is also affected by the external environment, and provides a buffer to external challenge, and thus the gut microbiota reflects an individual's personal experience. Moreover, the immune system undergoes a series of changes with age, which are related to chronic inflammation in the elderly. The formation, maturation and senescence of the intestinal immune system is closely related to the gut microbiota. Additionally, changes in the gut microbiota of elderly individuals may modulate the immune system, which may in turn affect health status. Herein, we summarize the correlations between the gut microbiota with individual health status in the elderly and explore the related mechanisms, which may provide a basis to maintain or enhance the health of the elderly though interventions targeting the gut microbiota.

Paeoniflorin regulates gut microbiota and bile acids metabolism in colitis mice / 药学学报

The current study was designed to evaluate the modulatory effects of paeoniflorin on the dysregulated gut microbiota as well as the disturbed fecal bile acids (BAs) in colitis mice. After approved by Xi'an Jiaotong University Ethics Committees (Approval No. XJTU2019-679), the animals were randomly distributed into the control (Con), colitis, low dose paeoniflorin (PF-L, 25 mg·kg-1·d-1), high dose paeoniflorin (PF-H, 50 mg·kg-1·d-1) and 5-aminosalicylic acid (5-ASA, 50 mg·kg-1·d-1) groups. Colitis was induced by administering 3% (w/v) DSS in drinking water for 7 days. Paeoniflorin and 5-ASA were dissolved in water and administered to the appropriate groups by oral gavage over the 7-day period. The mice were monitored daily, and the disease activity index (DAI) comprising of body weight loss, stool consistency and gross blood was measured. The pathological changes of colon were evaluated by HE staining; the levels of inflammatory cytokines in colonic tissue were determined by ELISA; the gut permeability was measured by FITC-dextran. Microbiota analysis based on 16S rDNA and targeted metabolomics for BAs were used to evaluate the composition of gut microbiota and fecal BAs pool. The results showed that administration of paeoniflorin markedly alleviated the inflammatory response and intestinal barrier dysfunction in DSS-induced colitis. Importantly, these ameliorative effects of paeoniflorin were accompanied by the improvements of disturbed composition of gut microbiota and the dysmetabolism of bile acids in feces. Finally, we performed Spearman's correlation analysis between the fecal BAs and gut microbiota genera, and found that Lactobacillus has a strong positive correlation with DCA and LCA which were reported to confer the beneficial effects of maintaining intestinal homeostasis. Taken together, paeoniflorin might improve the intestinal homeostasis in colitis mice via modulating gut microbiota and fecal BAs metabolism.

A narrative review of the role of fibroblasts in the growth and development of neurogenic tumors.

Neurogenic tumors, a group of tumors arising from neurogenic elements, could theoretically appear in every region of human bodies wherever nerves exist. Patients with these tumors suffer from both physical and psychological problems. However, as a relatively rare tumor type, therapies are relatively scarce for these tumors due to the limited understanding of the underlying mechanisms. Recently, a tailored tumor microenvironment containing multiple types of nonneoplastic cells has been considered to play an essential role in tumor survival, growth, and metastasis. Fibroblasts are a crucial constituent of the tumor microenvironment and have been found to promote tumor growth via multiple mechanisms. However, the understanding of the pivotal role of fibroblasts in the tumorigenesis and development of the neurogenic tumors is still incomplete, and studies in this area show differences in rates of progression among different neurogenic tumor subtypes. Nevertheless, all these neural crest-originated neoplasms show some similarities in the tumor microenvironment, indicating that studies of one subtype of neurogenic tumor might assist in clarifying the underlying mechanisms of other subtypes. This review aims to provide current studies showing the impacts of fibroblasts on major benign/malignant subtypes of neurogenic tumors, including neurofibromatosis type 1, neuroblastomas, pheochromocytomas, and malignant peripheral nerve sheath tumors. Multiple related mechanisms such as the fibroblasts regulating the tumor inflammation, angiogenesis, metabolism, and microenvironment establishment have been studied up to present. Consistently, we focus on how studies on various subtypes of these neurogenic tumors contribute to the establishment of potential future directions for further studies in this area. Clarifying the underlying mechanisms by which fibroblasts promote the growth and metastasis of neurogenic tumors will indicate new therapeutic targets for further clinical treatment.

Computed Tomography-Based Differentiation of Benign and Malignant Craniofacial Lesions in Neurofibromatosis Type I Patients: A Machine Learning Approach.

Background: Because neurofibromatosis type I (NF1) is a cancer predisposition disease, it is important to distinguish between benign and malignant lesions, especially in the craniofacial area. Purpose: The purpose of this study is to improve effectiveness in the diagnostic performance in discriminating malignant from benign craniofacial lesions based on computed tomography (CT) using a Keras-based machine-learning model. Methods: The Keras-based machine learning technique, a neural network package in the Python language, was used to train the diagnostic model on CT datasets. Fifty NF1 patients with benign craniofacial neurofibromas and six NF1 patients with malignant peripheral nerve sheath tumors (MPNSTs) were selected as the training set. Three validation cohorts were used: validation cohort 1 (random selection of 90% of the patients in the training cohort), validation cohort 2 (an independent cohort of 9 NF1 patients with benign craniofacial neurofibromas and 11 NF1 patients with MPNST), and validation cohort 3 (eight NF1 patients with MPNST, not restricted to the craniofacial area). Sensitivity and specificity were tested using validation cohorts 1 and 2, and generalizability was evaluated using validation cohort 3. Results: A total of 59 NF1 patients with benign neurofibroma and 23 NF1 patients with MPNST were included. A Keras-based machine-learning model was successfully established using the training cohort. The accuracy was 96.99 and 100% in validation cohorts 1 and 2, respectively, discriminating NF1-related benign and malignant craniofacial lesions. However, the accuracy of this model was significantly reduced to 51.72% in the identification of MPNSTs in different body regions. Conclusion: The Keras-based machine learning technique showed the potential of robust diagnostic performance in the differentiation of craniofacial MPNSTs and benign neurofibromas in NF1 patients using CT images. However, the model has limited generalizability when applied to other body areas. With more clinical data accumulating in the model, this system may support clinical doctors in the primary screening of true MPNSTs from benign lesions in NF1 patients.

Luteoloside Exerts Analgesic Effect in a Complete Freund's Adjuvant-Induced Inflammatory Model via Inhibiting Interleukin-1ß Expression and Macrophage/Microglia Activation.

BACKGROUND: Flavonoid monomers are proved to have an anti-inflammatory effect and may also be promising for chronic pain treatment. In the present study, the analgesic effect and the relevant mechanisms of luteoloside, one of the flavonoid monomers, were investigated. METHODS: The analgesic effect of luteoloside was first evaluated in complete Freud's adjuvant induced inflammatory model by von Frey test and Hargreaves test in both male and female mice. The interleukin-1ß levels in plantar tissue, serum, dorsal root ganglion, and the dorsal horn of the spinal cord were determined by enzyme-linked immunosorbent assay or immunofluorescence. The activation of macrophage/microglia was tested by Iba-1 staining. RESULTS: Our data showed that luteoloside exhibited both acute and chronic analgesic phenotypes. Every single dose of luteoloside solution reached the peak transient analgesic effect 2 h after administration and lasted less than 6 h. About 14 consecutive days administration (one dose per day) later, luteoloside showed a sustained analgesic effect which lasted more than 24 h. Celecoxib 20 mg/kg combined with luteoloside 40 mg/kg achieved a similar analgesic effect as celecoxib 40 mg/kg alone. Luteoloside inhibited interleukin-1ß expression in plantar tissue, dorsal root ganglion, the dorsal horn of spinal cord, and serum, after 14 days of continuous administration. Furthermore, our results also showed that the activation of macrophage/microglia in dorsal root ganglions were significantly inhibited 2 h after each single dose in daily luteoloside administration and recovered to a higher level 6 h later. These findings might be involved in the mechanisms of the acute analgesic effect of luteoloside. CONCLUSION: Luteoloside presents an analgesic effect via anti-inflammatory and other mechanisms such as inhibiting the activation of macrophage/microglia.

Safety and efficacy of metformin in systemic lupus erythematosus: a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Immunometabolism is involved in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to repurpose metformin, an anti-diabetic drug that regulates systemic and cellular metabolism, and assess its effects in Chinese patients with SLE without diabetes. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled trial in three hospitals in Shanghai, China. We enrolled adult patients with SLE, without diabetes, who had Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores no higher than 6; with no A score or no more than one B score on the British Isles Lupus Assessment Group (BILAG) scale at screening; who had had at least one lupus flare; and were treated with prednisone (≥20 mg per day) within the preceding 12 months. Patients were randomly assigned (1:1) in blocks of four by a computer algorithm to add metformin tablets (250 mg per tablet with a target dose of 0·5 g three times per day; metformin group) or placebo tablets (placebo group) to their standard therapy, for a maximum of 12 months. Patients, assessment staff, and statisticians were masked to group assignment. The primary endpoint was a composite index of major or mild-to-moderate disease flares (SELENA-SLEDAI Flare Index) at 12 months. The full analyses were done in all patients who received at least one dose of the study drug using the χ2 test. Adverse events were recorded during the 12-month follow-up. This study is registered with ClinicalTrials.gov, NCT02741960. FINDINGS: Between May 24, 2016, and Dec 13, 2017, 180 patients were screened, of whom 140 (78%) of them were enrolled. 31 (17%) did not meet the inclusion criteria and nine (5%) withdrew informed consent without treatment after randomisation. 67 patients were assigned to the metformin group and 73 to the placebo group. By 12 months of follow-up, there was no significant difference in the incidence of lupus flares, which occurred in 14 (21%) patients in the metformin group versus 25 (34%) in the placebo group (relative risk 0·68, 0·42-1·04, p=0·078). Patients receiving metformin experienced more gastrointestinal adverse events (three [4%] discontinued for this reason vs one [1%] for placebo; overall 26 [39%] vs 11 [15%], p=0·0015), but the incidence of non-flare serious adverse events was similar between groups (one [1%] vs three [4%], p=0·35). The frequency of infection events was significantly lower in patients in the metformin group than in the placebo group (17 [25%] vs 32 [44%], p=0·022). No patients died as a result of treatment. INTERPRETATION: This trial was underpowered to draw a sound conclusion on the efficacy of metformin to reduce disease flares as an add-on treatment to standard care in patients with SLE. Nonetheless, metformin had a favourable safety profile and our data present a basis for larger trials to investigate its potential effect on reducing the frequency of flares for patients with SLE with low-grade disease activity who are at risk of relapse. FUNDING: Shanghai Shenkang Promoting Project and the National Key Research and Development Program of China.

Low GRK2 Underlies Hyperalgesic Priming by Glial Cell-Derived Neurotrophic Factor.

Background: We recently identified the balance between the level of G protein coupled receptor kinase 2 (GRK2) and Epac1 in nociceptors as a key factor in the transition from acute to chronic pain that occurs in mice 'primed' by an inflammatory stimulus. Here, we examined the contribution of GRK2 and Epac-signaling to growth factor-induced hyperalgesic priming. Methods: Mice were primed by intraplantar injection with glial cell-derived neurotrophic factor (GDNF). Mechanical allodynia in response to PGE2 was followed over time in primed and non-primed animals. GRK2 protein levels in dorsal root ganglion (DRG) neurons were quantified by immunohistochemistry. The effect of herpes simplex virus (HSV)-GRK2 amplicons to restore GRK2 levels or of an Epac inhibitor on PGE2 allodynia in primed mice was examined. Results: Glial cell-derived neurotrophic factor-induced hyperalgesia disappeared within 12 days. The hyperalgesic response to a subsequent intraplantar injection of PGE2 was prolonged from <24 h in control mice to more than 72 h in GDNF-primed mice. In male and female primed mice, PGE2 hyperalgesia was inhibited by oral administration of the Epac inhibitor ESI-09, while the drug had no effect in control mice. Mice primed with GDNF had reduced levels of GRK2 in IB4(+) small DRG neurons, but normal GRK2 levels in IB4(-) DRG neurons. Intraplantar administration of HSV-GRK2 amplicons to increase GRK2 protein levels prevented the prolongation of PGE2-induced hyperalgesia in GDNF-primed mice. Conclusion: Low GRK2 in nociceptors is critical to develop a primed state in response to GDNF and leads to engagement of Epac signaling and transition to chronic PGE2-induced hyperalgesia. Increasing GRK2 protein or inhibiting Epac signaling may represent new avenues for preventing transition to a chronic pain state.

Luteolin-7-O-Glucoside Present in Lettuce Extracts Inhibits Hepatitis B Surface Antigen Production and Viral Replication by Human Hepatoma Cells in Vitro.

Hepatitis B virus (HBV) infection is endemic in Asia and chronic hepatitis B (CHB) is a major public health issue worldwide. Current treatment strategies for CHB are not satisfactory as they induce a low rate of hepatitis B surface antigen (HBsAg) loss. Extracts were prepared from lettuce hydroponically cultivated in solutions containing glycine or nitrate as nitrogen sources. The lettuce extracts exerted potent anti-HBV effects in HepG2 cell lines in vitro, including significant HBsAg inhibition, HBV replication and transcription inhibition, without exerting cytotoxic effects. When used in combination interferon-alpha 2b (IFNα-2b) or lamivudine (3TC), the lettuce extracts synergistically inhibited HBsAg expression and HBV replication. By using differential metabolomics analysis, Luteolin-7-O-glucoside was identified and confirmed as a functional component of the lettuce extracts and exhibited similar anti-HBV activity as the lettuce extracts in vitro. The inhibition rate on HBsAg was up to 77.4%. Moreover, both the lettuce extracts and luteolin-7-O-glucoside functioned as organic antioxidants and, significantly attenuated HBV-induced intracellular reactive oxygen species (ROS) accumulation. Luteolin-7-O-glucoside also normalized ROS-induced mitochondrial membrane potential damage, which suggests luteolin-7-O-glucoside inhibits HBsAg and HBV replication via a mechanism involving the mitochondria. Our findings suggest luteolin-7-O-glucoside may have potential value for clinical application in CHB and may enhance HBsAg and HBV clearance when used as a combination therapy.

Red light at intensities above 10 lx alters sleep-wake behavior in mice.

Sleep is regulated by two mechanisms: the homeostatic process and the circadian clock. Light affects sleep and alertness by entraining the circadian clock, and acutely inducing sleep/alertness, in a manner mediated by intrinsically photosensitive retinal ganglion cells. Because intrinsically photosensitive retinal ganglion cells are believed to be minimally sensitive to red light, which is widely used for illumination to reduce the photic disturbance to nocturnal animals during the dark phase. However, the appropriate intensity of the red light is unknown. In the present study, we recorded electroencephalograms and electromyograms of freely moving mice to investigate the effects of red light emitted by light-emitting diodes at different intensities and for different durations on the sleep-wake behavior of mice. White light was used as a control. Unexpectedly, red light exerted potent sleep-inducing effects and changed the sleep architecture in terms of the duration and number of sleep episodes, the stage transition, and the EEG power density when the intensity was >20 lx. Subsequently, we lowered the light intensity and demonstrated that red light at or below 10 lx did not affect sleep-wake behavior. White light markedly induced sleep and disrupted sleep architecture even at an intensity as low as 10 lx. Our findings highlight the importance of limiting the intensity of red light (⩽10 lx) to avoid optical influence in nocturnal behavioral experiments, particularly in the field of sleep and circadian research.

Asymmetric Michael Addition Induced by (R)-tert-Butanesulfinamide and Syntheses of Chiral Pyrazolidinone Derivatives.

A highly diastereoselective Michael addition of (R)-N-tert-butanesulfinyl imidates 8 to α,ß-unsaturated pyrazolidinone 3a has been developed to afford pyrazolidinones 10 possessing three contiguous stereocenters with good to excellent yield and excellent diastereoselectivity. A two-step conversion of reduction and cyclization provides the bicyclic pyrazolopiperidine 12 in a good yield. A series of pyrazolopiperidine derivatives 18 with a quaternary carbon center at C-3a are stereoselectively synthesized via alkylation or Michael addition.

Total Synthesis of Lignan Lactone (-)-Hinokinin.

This research paper is aimed at studying the total synthesis of pharmacologically active lignan (-)-hinokinin. The synthesis features a three-step cascade reaction involving highly stereoselective Michael addition, anion-oxidative hydroxylation, and oxygen anion cyclization to construct the pivotal butyrolactonimidate intermediate.

Gelsemine alleviates both neuropathic pain and sleep disturbance in partial sciatic nerve ligation mice.

AIM: Gelsemine, an alkaloid from the Chinese herb Gelsemium elegans (Gardn & Champ) Benth., is effective in mitigating chronic pain in rats. In the present study we investigated whether the alkaloid improved sleep disturbance, the most common comorbid symptoms of chronic pain, in a mouse model of neuropathic pain. METHODS: Mice were subjected to partial sciatic nerve ligation (PSNL). After the mice were injected with gelsemine or pregabalin (the positive control) intraperitoneally, mechanical allodynia and thermal hyperalgesia were assessed, and electroencephalogram (EEG)/electromyogram (EMG) recording was performed. Motor performance of the mice was assessed using rota-rod test. c-Fos expression in the brain was analyzed with immunohistochemical staining. RESULTS: In PSNL mice, gelsemine (2 and 4 mg/kg) increased the mechanical threshold for 4 h and prolonged the thermal latencies for 3 h. Furthermore, gelsemine (4 mg/kg, administered at 6:30 AM) increased non-rapid eye movement (non-REM, NREM) sleep, decreased wakefulness, but did not affect REM sleep during the first 3 h in PSNL mice. Sleep architecture analysis showed that gelsemine decreased the mean duration of wakefulness and increased the total number of episodes of NREM sleep during the first 3 h after the dosing. Gelsemine (4 mg/kg) did not impair motor coordination in PSNL mice. Immunohistochemical study showed that PSNL increased c-Fos expression in the neurons of the anterior cingulate cortex, and gelsemine (4 mg/kg) decreased c-Fos expression by 58%. Gelsemine (4 mg/kg, administered at either 6:30 AM or 8:30 PM) did not produce hypnotic effect in normal mice. Pregabalin produced similar antinociceptive and hypnotic effects, but impaired motor coordination in PSNL mice. CONCLUSION: Gelsemine is an effective agent for treatment of both neuropathic pain and sleep disturbance in PSNL mice; anterior cingulate cortex might play a role in the hypnotic effects of gelsemine.

Nutritional aspects of ß-carotene and resveratrol antioxidant synergism in giant unilamellar vesicles.

Giant unilamellar vesicles of soy phosphatidylcholine are found to undergo budding when sensitized with chlorophyll a ([phosphatidylcholine] : [chlorophyll a] = 1500 : 1) under light irradiation (400-440 nm, 16 mW mm(-2)). 'Entropy' as a dimensionless image heterogeneity measurement is found to increase linearly with time during an initial budding process. For ß-carotene addition ([phosphatidylcholine] : [ß-carotene] = 500 : 1), a lag phase of 23 s is observed, followed by a budding process at an initial rate lowered by a factor of 3.8, whereas resveratrol ([phosphatidylcholine] : [resveratrol] = 500 : 1) has little if any protective effect against budding. However, resveratrol, when combined with ß-carotene, is found to further reduce the initial budding rate by a total factor of 4.7, exhibiting synergistic antioxidation effects. It is also interesting that ß-carotene alone determines the lag phase for the initiation of budding, while resveratrol supports ß-carotene in reducing the rate of the budding process following the lag phase; however, it alone has no observable effect on the lag phase. Resveratrol is suggested to regenerate ß-carotene following its sacrificial protection of unsaturated lipids from oxidative stress, modeling the synergistic effects in cell membranes by combinations of dietary antioxidants.

A review of clinical and histological parameters associated with contralateral neck metastases in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) has a high incidence of cervical micrometastases and sometimes metastasizes contralaterally because of the rich lymphatic intercommunications relative to submucosal plexus of oral cavity that freely communicate across the midline, and it can facilitate the spread of neoplastic cells to any area of the neck consequently. Clinical and histopathologic factors continue to provide predictive information to contralateral neck metastases (CLNM) in OSCC, which determine prophylactic and adjuvant treatments for an individual patient. This review describes the predictive value of clinical-histopathologic factors, which relate to primary tumor and cervical lymph nodes, and surgical dissection and adjuvant treatments. In addition, the indications for elective contralateral neck dissection and adjuvant radiotherapy (aRT) and strategies for follow-up are offered, which is strongly focused by clinicians to prevent later CLNM and poor prognosis subsequently.

Use of the contralateral retroangular island flap for reconstructing midfacial defects after skin cancer ablation.

BACKGROUND: The retroangular flap is usually used to reconstruct small ipsilateral facial defects. The purpose of this study was to explore the use of the contralateral retroangular island flap for reconstructing large midfacial defects. METHODS: Retroangular flaps raised from the contralateral infraorbital region were used to reconstruct midfacial defects in 12 patients after the resection of skin cancers. The defect ranged in size from 3.0 × 3.0 to 5.0 × 7.0 cm, and the flap skin paddle ranged in size from 2.0 × 4.0 to 4.0 × 6.0 cm. RESULTS: All of the flaps survived. Patients were followed up for an average of 8.5 months. The vascularity of the flaps was good, and the match in terms of color and texture was excellent. The cosmetic and functional outcomes were satisfactory in all patients. CONCLUSION: The contralateral retroangular flap is a good alternative for reconstructing moderate to large midfacial defects.