Oral squamous cell carcinoma(OSCC)is one of the most prevalent forms of head and neck squamous cell carcinomas(HNSCC)with a poor overall survival rate(about 50%),particularly in cases of metastasis.RNA-based cancer bi...Oral squamous cell carcinoma(OSCC)is one of the most prevalent forms of head and neck squamous cell carcinomas(HNSCC)with a poor overall survival rate(about 50%),particularly in cases of metastasis.RNA-based cancer biomarkers are a relatively advanced concept,and non-coding RNAs currently have shown promising roles in the detection and treatment of various malignancies.This review underlines the function of long non-coding RNAs(lncRNAs)in the OSCC and its subsequent clinical implications.LncRNAs,a class of non-coding RNAs,are larger than 200 nucleotides and resemble mRNA in numerous ways.However,unlike mRNA,lncRNA regulates multiple druggable and non-druggable signaling molecules through simultaneous interaction with DNA,RNA,proteins,or microRNAs depending on concentration and localization in cells.Upregulation of oncogenic lncRNAs and downregulation of tumor suppressor lncRNAs are evident in OSCC tissues and body fluids such as blood and saliva indicating their potential as valuable biomarkers.Targeted inhibition of candidate oncogenic lncRNAs or overexpression of tumor suppressor lncRNAs showed potential therapeutic roles in in-vivo animal models.The types of lncRNAs that are expressed differentially in OSCC tissue and bodily fluids have been systematically documented with specificity and sensitivity.This review thoroughly discusses the biological functions of such lncRNAs in OSCC cell survival,proliferation,invasion,migration,metastasis,angiogenesis,metabolism,epigenetic modification,tumor immune microenvironment,and drug resistance.Subsequently,we addressed the diagnostic and therapeutic importance of lncRNAs in OSCC pre-clinical and clinical systems,providing details on ongoing research and outlining potential future directions for advancements in this field.In essence,this review could be a valuable resource by offering comprehensive and current insights into lncRNAs in OSCC for researchers in fundamental and clinical domains.展开更多
Background:Mesenchymal stem cells(MSCs)from type 2 diabetes mellitus(T2DM)individuals exhibit increased adipogenesis and decreased osteogenesis.We investigated the potential of adipose tissue-derived MSCs(ADMSCs)secre...Background:Mesenchymal stem cells(MSCs)from type 2 diabetes mellitus(T2DM)individuals exhibit increased adipogenesis and decreased osteogenesis.We investigated the potential of adipose tissue-derived MSCs(ADMSCs)secretome obtained from healthy individuals in restoring the tumor necrosis factor-α(TNF-α)mediated imbalance in the adipo/osteogenic differentiation in the dental pulp-derived MSCs obtained from T2DM individuals(dDPMSCs).Methods:dDPMSCs were differentiated into adipocytes and osteocytes using a standard cocktail in the presence of(a)induction cocktail,(b)induction cocktail+TNF-α,and(c)induction cocktail+TNF-α+ADMSCs-secretome(50%)for 15 and 21 days resp.Differentiated adipocytes and osteocytes were stained by oil red O and alizarin red and analyzed by using ImageJ software.Molecular expression of the key genes involved was analyzed by using reverse-transcription polymerase chain reaction(RT-PCR).Results:Treatment of TNF-αaugmented the adipogenesis(9571±765 vs.19,815±1585 pixel,p<0.01)and decreased the osteogenesis(15,603±1248 vs.11,894±951 pixel,p<0.05)of dDPMSCs as evidenced by the oil red O and alizarin red staining respectively.Interestingly,dDPMSCs differentiated along with TNF-αand 50%ADMSCs secretome exhibited enhanced osteogenesis(11,894±951 vs.41,808±3344 pixel,p<0.01)and decreased adipogenesis(19,815±1585 vs.4480±358 pixel,p<0.01).Additionally,dDPMSCs differentiated along with ADMSCs secretome exhibited decreased expression of PPARg(p<0.01),C/EBPa(p<0.05),and FAS(p<0.01)whereas mRNA expression of Runx2(p<0.05),Osterix(p<0.01),and OCN(p<0.05)was upregulated as revealed by the RT-PCR analysis.Conclusion:ADMSCs secretome from healthy individuals restore the TNF-αinfluenced differentiation fate of dDPMSCs and therefore can be explored for T2DM clinical management in the future.展开更多
Background: Pharmacological factors used to induce insulin resistance (IR) inin vitro models may not mimic the fullin vivo features of type 2 diabetes mellitus (T2DM). This study aimed to examine the ability of diabet...Background: Pharmacological factors used to induce insulin resistance (IR) inin vitro models may not mimic the fullin vivo features of type 2 diabetes mellitus (T2DM). This study aimed to examine the ability of diabetic serum (DS) to induce IR and investigate whether adipose-derived mesenchymal stem cell conditioned medium (ADMSC-CM) reverses DS-induced IR.Methods: DS was obtained from newly diagnosed T2DM patients. IR was induced in differentiated 3T3-L1 cells by employing dexamethasone, tumor necrosis factor alpha (TNF-α), palmitate and DS. Glucose uptake (2-[N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl] amino]-2-deoxyglucose(2-NBDG) uptake assay), intracellular levels of reactive oxygen species (ROS), and superoxide radicals (O2-) (fluorescence microscopy and fluorometry) were analyzed in control and experimental samples. mRNA expression of key genes involved in glucose transport and inflammation were analyzed by using reverse transcription polymerase chain reaction (RT-PCR). Pro-inflammatory cytokines and phospho-insulin receptor substrate (IRS) (Ser-307) protein expression were analyzed by fluorescence activated cell sorter analysis. Statistical significance was determined by using one-way ANOVA followed by Tukey’s multiple comparison tests.Results: ADMSC-CM significantly increased the DS-mediated decrease in 2-NBDG uptake (11.01 ± 0.50vs. 7.20 ± 0.30,P < 0.01) and reduced DS-driven ROS (fluorescence count, 6.35 ± 0.46vs. 9.80 ± 0.10,P < 0.01) and O2- (fluorescence count, 3.00 ± 0.10vs. 4.60 ± 0.09,P < 0.01) production. Further, the ADMSC-CM restored DS-induced down regulation GLUT4 (1.52- fold,P < 0.05) as well as the up-regulation of PPARγ (0.35-fold,P < 0.01), and IKKβ (0.37-fold,P < 0.01) mRNA, and phospho-IRS (Ser-307) protein expression compared to the baseline (median fluorescence intensity, 88,192 ± 2720vs. 65,450 ± 3111,P < 0.01). DS induced IR, similar to the traditionally used pharmacological factors, namely dexamethasone, TNF-α, and palmitate, which can be attributed to the significantly higher pro-inflammatory cytokines levels (TNF-α (2.28 ± 0.03 pg/mLvs. 2.38 ± 0.03 pg/mL,P < 0.01), interleukin 6 (IL)-6 (1.94 ± 0.02 pg/mLvs. 2.17 ± 0.04 pg/mL,P < 0.01), IL-17 (2.16 ± 0.02 pg/mLvs. 2.22 ± 0.002 pg/mL,P < 0.05), and interferon gamma (IFN-γ) (2.07 ± 0.02 pg/mLvs. 2.15 ± 0.04 pg/mL,P < 0.05)) in DS.Conclusions: DS can be explored as a novel inducer of IR inin vitro studies with further standardization, substituting the conventionally used pharmacological factors. Our findings also affirm the validity of ADMSC-CM as a prospective insulin sensitizer for T2DM therapy.展开更多
基金the Ramalingaswami Re-Entry Fellowship,Department of Biotechnology,Govt.of India to S.Sur(BT/RLF/Re-Entry/47/2021).
文摘Oral squamous cell carcinoma(OSCC)is one of the most prevalent forms of head and neck squamous cell carcinomas(HNSCC)with a poor overall survival rate(about 50%),particularly in cases of metastasis.RNA-based cancer biomarkers are a relatively advanced concept,and non-coding RNAs currently have shown promising roles in the detection and treatment of various malignancies.This review underlines the function of long non-coding RNAs(lncRNAs)in the OSCC and its subsequent clinical implications.LncRNAs,a class of non-coding RNAs,are larger than 200 nucleotides and resemble mRNA in numerous ways.However,unlike mRNA,lncRNA regulates multiple druggable and non-druggable signaling molecules through simultaneous interaction with DNA,RNA,proteins,or microRNAs depending on concentration and localization in cells.Upregulation of oncogenic lncRNAs and downregulation of tumor suppressor lncRNAs are evident in OSCC tissues and body fluids such as blood and saliva indicating their potential as valuable biomarkers.Targeted inhibition of candidate oncogenic lncRNAs or overexpression of tumor suppressor lncRNAs showed potential therapeutic roles in in-vivo animal models.The types of lncRNAs that are expressed differentially in OSCC tissue and bodily fluids have been systematically documented with specificity and sensitivity.This review thoroughly discusses the biological functions of such lncRNAs in OSCC cell survival,proliferation,invasion,migration,metastasis,angiogenesis,metabolism,epigenetic modification,tumor immune microenvironment,and drug resistance.Subsequently,we addressed the diagnostic and therapeutic importance of lncRNAs in OSCC pre-clinical and clinical systems,providing details on ongoing research and outlining potential future directions for advancements in this field.In essence,this review could be a valuable resource by offering comprehensive and current insights into lncRNAs in OSCC for researchers in fundamental and clinical domains.
基金Council of Scientific and Industrial Research(CSIR),Government of India。
文摘Background:Mesenchymal stem cells(MSCs)from type 2 diabetes mellitus(T2DM)individuals exhibit increased adipogenesis and decreased osteogenesis.We investigated the potential of adipose tissue-derived MSCs(ADMSCs)secretome obtained from healthy individuals in restoring the tumor necrosis factor-α(TNF-α)mediated imbalance in the adipo/osteogenic differentiation in the dental pulp-derived MSCs obtained from T2DM individuals(dDPMSCs).Methods:dDPMSCs were differentiated into adipocytes and osteocytes using a standard cocktail in the presence of(a)induction cocktail,(b)induction cocktail+TNF-α,and(c)induction cocktail+TNF-α+ADMSCs-secretome(50%)for 15 and 21 days resp.Differentiated adipocytes and osteocytes were stained by oil red O and alizarin red and analyzed by using ImageJ software.Molecular expression of the key genes involved was analyzed by using reverse-transcription polymerase chain reaction(RT-PCR).Results:Treatment of TNF-αaugmented the adipogenesis(9571±765 vs.19,815±1585 pixel,p<0.01)and decreased the osteogenesis(15,603±1248 vs.11,894±951 pixel,p<0.05)of dDPMSCs as evidenced by the oil red O and alizarin red staining respectively.Interestingly,dDPMSCs differentiated along with TNF-αand 50%ADMSCs secretome exhibited enhanced osteogenesis(11,894±951 vs.41,808±3344 pixel,p<0.01)and decreased adipogenesis(19,815±1585 vs.4480±358 pixel,p<0.01).Additionally,dDPMSCs differentiated along with ADMSCs secretome exhibited decreased expression of PPARg(p<0.01),C/EBPa(p<0.05),and FAS(p<0.01)whereas mRNA expression of Runx2(p<0.05),Osterix(p<0.01),and OCN(p<0.05)was upregulated as revealed by the RT-PCR analysis.Conclusion:ADMSCs secretome from healthy individuals restore the TNF-αinfluenced differentiation fate of dDPMSCs and therefore can be explored for T2DM clinical management in the future.
文摘Background: Pharmacological factors used to induce insulin resistance (IR) inin vitro models may not mimic the fullin vivo features of type 2 diabetes mellitus (T2DM). This study aimed to examine the ability of diabetic serum (DS) to induce IR and investigate whether adipose-derived mesenchymal stem cell conditioned medium (ADMSC-CM) reverses DS-induced IR.Methods: DS was obtained from newly diagnosed T2DM patients. IR was induced in differentiated 3T3-L1 cells by employing dexamethasone, tumor necrosis factor alpha (TNF-α), palmitate and DS. Glucose uptake (2-[N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl] amino]-2-deoxyglucose(2-NBDG) uptake assay), intracellular levels of reactive oxygen species (ROS), and superoxide radicals (O2-) (fluorescence microscopy and fluorometry) were analyzed in control and experimental samples. mRNA expression of key genes involved in glucose transport and inflammation were analyzed by using reverse transcription polymerase chain reaction (RT-PCR). Pro-inflammatory cytokines and phospho-insulin receptor substrate (IRS) (Ser-307) protein expression were analyzed by fluorescence activated cell sorter analysis. Statistical significance was determined by using one-way ANOVA followed by Tukey’s multiple comparison tests.Results: ADMSC-CM significantly increased the DS-mediated decrease in 2-NBDG uptake (11.01 ± 0.50vs. 7.20 ± 0.30,P < 0.01) and reduced DS-driven ROS (fluorescence count, 6.35 ± 0.46vs. 9.80 ± 0.10,P < 0.01) and O2- (fluorescence count, 3.00 ± 0.10vs. 4.60 ± 0.09,P < 0.01) production. Further, the ADMSC-CM restored DS-induced down regulation GLUT4 (1.52- fold,P < 0.05) as well as the up-regulation of PPARγ (0.35-fold,P < 0.01), and IKKβ (0.37-fold,P < 0.01) mRNA, and phospho-IRS (Ser-307) protein expression compared to the baseline (median fluorescence intensity, 88,192 ± 2720vs. 65,450 ± 3111,P < 0.01). DS induced IR, similar to the traditionally used pharmacological factors, namely dexamethasone, TNF-α, and palmitate, which can be attributed to the significantly higher pro-inflammatory cytokines levels (TNF-α (2.28 ± 0.03 pg/mLvs. 2.38 ± 0.03 pg/mL,P < 0.01), interleukin 6 (IL)-6 (1.94 ± 0.02 pg/mLvs. 2.17 ± 0.04 pg/mL,P < 0.01), IL-17 (2.16 ± 0.02 pg/mLvs. 2.22 ± 0.002 pg/mL,P < 0.05), and interferon gamma (IFN-γ) (2.07 ± 0.02 pg/mLvs. 2.15 ± 0.04 pg/mL,P < 0.05)) in DS.Conclusions: DS can be explored as a novel inducer of IR inin vitro studies with further standardization, substituting the conventionally used pharmacological factors. Our findings also affirm the validity of ADMSC-CM as a prospective insulin sensitizer for T2DM therapy.
