查看更多>>摘要：Ginsenoside Rg3 (GRg3) is a ginsenoside extracted from Panax ginseng。 GRg3 displays multiple pharmacological properties， such as antitumor， anti-inflammatory， antioxidative and antifibrotic properties。 However， whether GRg3 inhibits angiogenesis in gastric precancerous lesions (GPLs) and the possible mechanisms remain unknown。 GRg3 attenuated gastric intestinal metaplasia and gastric dysplasia， the hallmark of GPL pathology， in rats with MNNG-ammonia compound induced GPLs。 Increased CD34+ microvessel density and VEGF expression， which indicate the presence of angiogenesis， were evident in the rats with GPLs。 GRg3 administration reduced VEGF protein expression and CD34+ microvessel density。 In addition， GRg3 was capable of attenuating microvascular abnormalities。 Data analysis revealed that enhanced protein expression of GLUT1， GLUT3 and GLUT4 were present in both human and animal GPL specimens。 The administration of GRg3 caused significant decreases in the mRNA and protein expression levels of GLUT1 and GLUT4 in the rats with GPLs。 However， the GRg3-treated rats with GPLs did not demonstrate regulatory effects on GLUT3， GLUT6， GLUT10， and GLUT12。 Consistent with in vitro results， GRg3 administration significantly reduced the protein expression levels of GLUT1 and GLUT4 in both AGS and HGC-27 human gastric cancer cells in vitro。 In conclusion， GRg3 can attenuate angiogenesis and temper microvascular abnormalities in rats with GPLs， which may be associated with its inhibition on the aberrant activation of GLUT1 and GLUT4。
Abdallah M. GendyMohamed R. ElnagarMona M. AllamMohamed R. Mousa...
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查看更多>>摘要：Objective: Berberine (BBR) is a known alkaloid that has verified its protective effects against ischemia/reperfusion (I/RN) lesion in multiple organs but its poor oral bioavailability limited its use。 Despite the previous works， its possible impact on the warm hepatic I/RN-induced lesion is not clear。 Accordingly， a nanostructured lipid carrier of BBR (NLC BBR) was developed for enhancing its efficiency and to inspect its protective mechanistic against warm hepatic I/RN。 Methods: NLC BBR formula was evaluated pharmaceutically。 Wistar rats were orally pre-treated with either BBR or NLC BBR (100 mg/kg) for 2 weeks followed by hepatic I/RN (30 min/24 h)。 Biochemical， ELISA， qPCR， western blot， histopathological， and immunohistochemical studies were performed。 Key findings: Optimized NLC BBR was prepared with a particle size of 130 ± 8。3 nm。 NLC BBR divulged its aptitude to safeguard the hepatic tissues partly due to anti-inflammatory capacity through downsizing the HMGB1/TLR4/NF-κB trajectory with concomitant rebating of TNF-α， iNOS， COX-2， and MPO content。 Furthermore， NLC BBR antiapoptotic trait was confirmed by boosting the prosurvival protein (Bcl-2) and cutting down the pro-apoptotic marker (Bax)。 Moreover， its antioxidant nature was confirmed by TAC uplifting besides MDA subsiding。 On the other hand， NLC BBR action embroiled autophagy flux spiking merit exemplified in Beclin-1 and LC3-II enhancement。 Finally， NLC BBR administration ascertained its hepatocyte guarding action by recovering the histopathological ailment and diminishing serum transaminases。 Conclusion: NLC BBR purveyed reasonable shielding mechanisms and subsided incidents contemporaneous to warm hepatic I/RN lesion in part， by moderating HMGB1/TLR4/NF-κB inflammatory signaling， autophagy， and apoptosis。
Zeynab KohelTahereh FarkhondehMichael AschnerAli Mohammad Pourbagher-Shahri...
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查看更多>>摘要：Astaxanthin (AST) is a red pigmented carotenoid with significant antioxidant， anti-inflammatory， anti-prolifer-ative， and anti-apoptotic properties。 In this study， we summarize the available literature on the anti-inflammatory efficacy of AST in various chronic and acute disorders， such as neurodegenerative， renal-， hep-ato-， skin- and eye-related diseases， as well as gastrointestinal disorders。 In addition， we elaborated on therapeutic efficacy of AST and the role of several pathways， including PI3K/AKT， Nrf2， NF-κB， ERK1/2， JNK， p38 MAPK， and JAK-2/STAT-3 in mediating its effects。 However， additional experimental and clinical studies should be performed to corroborate the anti- inflammatory effects and protective effects of AST against inflammatory diseases in humans。 Nevertheless， this review suggests that AST with its demonstrated anti-inflammatory property may be a suitable candidate for drug design with novel technology。
Gary A. LevyKadalraja RaghavanVidyasagar Devaprasad DedeepiyaVaddi Suryaprakash...
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查看更多>>摘要：Objective: In this pilot clinical study， we report the beneficial effects of beta glucans derived from two strains AFO-202 and N-163 of a black yeast Aureobasidium pullulans on the biomarkers for cytokine storm and coa-gulopathy in COVID-19 patients。 Methods: A total of 24 RT-PCR positive COVID-19 patients were recruited and randomly divided into three groups (Gr): Gr。 1 control (n = 8) - Standard treatment; Gr。 2: Standard treatment + AFO-202 beta glucan (n = 8); and Gr。 3， Standard treatment + combination of AFO-202 and N-163 beta glucans (n = 8) for 30 days。 Results: There was no mortality or requirement of ventilation of the subjects in any of the groups。 There was a decrease in D-Dimer values (751 ng/ml to 143。89 ng/ml) and IL-6 values (7。395-3。16 pg/ml) in Gr。 1 in 15 days but the levels increased to abnormal levels on day 30 (D-Dimer: 202。5 ng/ml; IL-6 55。37 pg/ml); which steadily decreased up to day 30 in groups 2 (D-dimer: 560。99 ng/dl to 79。615; IL-6: 26。18-3。41 pg/ml) and 3 (D-dimer: 1614 ng/dl to 164。25 ng/dl; IL-6: 6。25-0。5 pg/ml)。 The same trend was observed with ESR。 LCR and LeCR increased while NLR decreased significantly in Gr。 3。 CD4 + and CD8 + T cell count showed relatively higher increase in Gr。3。 There was no difference in CRP within the groups。 Conclusion: As these beta glucans are well known food supplements with a track record for safety， larger multi-centric clinical studies are recommended to validate their use as an adjunct in the management of COVID-19 and the ensuing long COVID-19 syndrome。
查看更多>>摘要：Cathepsin S (CTSS)， a lysosomal protease， belongs to a family of cysteine cathepsin proteases that promote degradation of damaged proteins in the endolysosomal pathway。 Aberrant CTSS expression and regulation are associated with the pathogenesis of several diseases， including lung diseases。 CTSS overexpression causes a variety of pathological processes， including pulmonary fibrosis， with increased CTSS secretion and accelerated extracellular matrix remodeling。 Compared to many other cysteine cathepsin family members， CTSS has unique features that it presents limited tissue expression and retains its enzymatic activity at a neutral pH， suggesting its decisive involvement in disease microenvironments。 In this review， we investigated the role of CTSS in lung disease， exploring recent studies that have indicated that CTSS mediates fibrosis in unique ways， along with its structure， substrates， and distinct regulation。 We also outlined examples of CTSS inhibitors in clinical and pre-clinical development and proposed CTSS as a potential therapeutic target for pulmonary fibrosis。
查看更多>>摘要：Advances in high-throughput sequencing over the past decades have led to the identification of thousands of non-coding RNAs (ncRNAs)， which play a major role in regulating gene expression。 One emerging class of ncRNAs is the natural antisense transcripts (NATs)， the RNA molecules transcribed from the opposite strand of a protein-coding gene locus。 NATs are known to concordantly and discordantly regulate gene expression in both cis and trans manners at the transcriptional， post-transcriptional， translational， and epigenetic levels。 Aberrant expression of NATs can therefore cause dysregulation in many biological pathways and has been observed in many genetic diseases。 This review outlines the involvements and mechanisms of NATs in the pathogenesis of various diseases， with a special emphasis on neurodegenerative diseases and cancer。 We also summarize recent findings on NAT knockdown and/or overexpression experiments and discuss the potential of NATs as promising targets for future gene therapies。
查看更多>>摘要：Ursolic acid (UA) is a natural compound that shows anti-inflammatory actions。 However， no human studies have investigated the cytokine profile during the RT and UA consumption。 The purpose of this study was to verify if UA is able to potentiate the anti-inflammatory activity after RT， reflecting in the reduction of blood inflammatory markers in healthy men。 Twenty-seven participants were allocated to two groups: control (CON) (n = 13) and UA (n = 14)。 For 8 weeks， each group performed RT and consumed capsules containing a placebo (400 mg/day) or UA (400 mg/day)。 Serum cytokine concentrations were evaluated before and after the training period。 There was no difference in the serum cytokine concentrations of TNF-α， IL-10 and IL-6 (p > 0。05)。 In conclusion， UA supplementation for 8 weeks was not able to change the blood TNF-α， IL-10， and IL-6 concentrations in healthy men undergoing RT。 However， further studies are warranted to investigate other inflammatory markers。
查看更多>>摘要：Diabetes has become more common in recent years worldwide， and this growth is projected to continue in the future。 The primary concern with diabetes is developing various complications， which significantly contribute to the disease's mortality and morbidity。 Over time， the condition progresses from the pre-diabetic to the diabetic stage and then to the development of complications。 Years and enormous resources are required to evaluate pharmacological interventions to prevent or delay the progression of disease or complications in humans。 Appropriate screening models are required to gain a better understanding of both pathogenesis and potential therapeutic agents。 Different species of animals are used to evaluate the pharmacological potentials and study the pathogenesis of the disease。 Animal models are essential for research because they represent most of the structural， functional， and biochemical characteristics of human diseases。 An ideal screening model should mimic the pathogenesis of the disease with identifiable characteristics。 A thorough understanding of animal models is required for the experimental design to select an appropriate model。 Each animal model has certain advantages and limitations。 The present manuscript describes the animal models and their diagnostic characteristics to evaluate microvascular diabetic complications。
查看更多>>摘要：An increasing number of epidemiological studies have shown that there is a significant inverse relationship between the onset of Alzheimer's disease/Parkinson's disease (AD/PD) and cancer， but the mechanism is still unclear。 Considering that intestinal flora can connect them， we tried to explain this phenomenon from the intestinal flora。 This review briefly introduced the relationship among AD/PD， cancer， and intestinal flora， studied metabolites or components of the intestinal flora and the role of intestinal barriers and intestinal hormones in AD/PD and cancer。 After screening， a part of the flora capable of participating in the occurrence processes of the three diseases at the same time was obtained， the abundance changes of the special flora in AD/PD and various types of cancers were summarized， and they were classified according to the flora function and abundance， which in turn innovatively and reasonably explained the fact that AD/PD and cancer showed certain antagonism in epidemiological statistics from the perspective of intestinal flora。 This review also proposed that viewing the risk relationship between diseases from the perspective of intestinal flora may provide new research ideas for the treatment of fecal microbiota transplantation (FMT) and related diseases。
查看更多>>摘要：Atopic dermatitis (AD) leads to skin barrier abnormalities and immune dysfunction。 As the topical steroids commonly used to treat AD have side effects from long-term use， research into safer treatments for AD is greatly needed。 The medicinal herb Gardenia jasminoides improves AD symptoms via skin barrier activation and T helper 2-mediated immune response regulation。 Crocin， a bioactive component within the extract， is dispensible for its restorative effects。 As such， this work explored the effects of Gardenia jasminoides extract without crocin (GjexCr) on AD symptoms in a DfE-induced AD model in 6-week-old male NC/Nga mice (25。0 ± 0。25 g， n = 10 each， 6 groups)。 Using histological and behavioral assays， the effects of GjexCr on dermatitis scores， scratching behavior， skin barrier activation， and serum levels of IgE， chemokines， and cytokines were analyzed。 In addition， the major components from the GjexCr extract were analyzed by high-performance liquid chromatography and validated in the AD model。 GjexCr reduced ear thickness due to hyperkeratosis， dermal thickening， and scratching behavior and restored dermatitis scores in AD-induced mice。 GjexCr administration also decreased inflammation and mast cell infiltration， as well as modulated skin barrier recovery by upregulating the production of epidermal proteins。 Moreover， GjexCr administration attenuated imbalanced immune responses。 Furthermore， geniposide， the main component of GjexCr， improved AD symptoms in DfE-treated NC/Nga mice。 Thus， GjexCr could be a suitable treatment for protecting the skin barrier in AD-like skin lesions and a potential therapy for AD。
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