Project description:IntroductionGiant condyloma acuminata (GCA), also known as Bushke-Lowenstein tumour, is a rare disease which affects 0.1% of the population. Although histopathologically benign, it tends to be locally destructive. The common sites of involvement include the penis and the anorectum. Due to the rarity of the disease, there is a lack of controlled studies on the optimal management of this entity. Thus, we report a case of anogenital GCA in a 40-year-old HIV-positive man.Case presentationA 40-year-old man presented with progressive anogenital warts associated with foul-smelling discharge and fever. He has been diagnosed with HIV and was on HAART on presentation. A warty excrescence had infiltrated the entire external genitalia, gluteals and sacral region. Serial excision was performed along with a defunctioning colostomy. The patient recovered well, and the final histopathological showed features of GCA.DiscussionWith HIV, the HPV infection goes unchecked may develop into GCA. Malignant transformation to squamous cell carcinoma may occur in more than half of the cases. A complex interaction between HIV and HPV may lead to a higher risk of recurrence even after resection. The diagnosis is usually clinical. Imaging modalities may be used in identifying the extent and depth of invasion.ConclusionThe optimal management of anogenital giant condyloma acuminata remains to be determined. Staged surgical excision should be conducted to achieve an optimum outcome. Radical reconstructive surgery should be reserved for patients with recurrence, malignant transformation or sphincter involvement.
Project description:Hailey-Hailey disease (HHD) is a rare autosomal-dominant blistering disorder characterized by recurrent vesicular and erosive lesions at intertriginous sites. We described a 24-year-old male who presented with multiple bright red verrucous papules in his mons pubis, bilateral groins, scrotum, perineum, and crissum, clinically resembling condyloma acuminatum. The histopathology showed extensive acantholysis with the characteristic appearance of a dilapidated brick-wall. The mutation analysis revealed a novel splice-site mutation in the ATP2C1 gene. The patient was definitely diagnosed with HHD. The antibacterial treatments resulted in a dramatic improvement. Our findings help to broaden the understanding of clinical manifestations of HHD and improve the clinical diagnosis and treatment of this disease.
Project description:The expression profile of miRNAs and their function in condyloma acuminatum (CA) remains unknown. In this study, we aimed to detect the effects of miR-143 and miR-145, the most downregulated in CA samples using high-throughput sequencing, on cell proliferation and apoptosis, to determine a novel therapeutic target for CA recurrence. RT-qPCR was used to validate the lower expression of miR-143 and miR-145 in a larger size of CA samples, and the expression of NRAS in CA samples was significantly higher than self-controls as determined by western blotting assay. Luciferase assay was performed to confirm that miR-143 or miR-145 targeted NRAS directly. Transduction of LV-pre-miR-143 or LV-pre-miR-145 to human papilloma virus (HPV)-infected SiHa cells led to reduced proliferation, greater apoptosis and inhibition of expression of NRAS, PI3 K p110? and p-AKT. However, knockout of miR-143 or miR-145 in human epidermal keratinocytes by delivery of CRISPR/CAS9-gRNA for target miRNAs protected cells from apoptosis and upregulated expression of target genes as described above. MiR-143 and miR-145 sensitized cells to nutlin-3a, a p53 activator and MDM2 antagonist, while their loss protected cells from the stress of nutlin-3a. Furthermore, siRNA targeting NRAS showed similar effects on proliferation and apoptosis as miR-143 or miR-145. Taken together, our results suggest that loss of miR-143 or miR-145 in CA protects HPV-infected cells from apoptosis induced by environmental stress, in addition to promoting cellular proliferation and inhibiting apoptosis by targeting NRAS/PI3 K/ATK. Restoration of miR-143 or miR-145 might provide an applicable and novel approach to block the recurrence and progression of CA.
Project description:BackgroundCondyloma acuminatum (CA) is a sexually transmitted disease characterized by the anomalous proliferation of keratinocytes caused by human papillomavirus (HPV) infection. Fu Fang Gang Liu liquid (FFGL) is an effective externally administered prescription used to treat CA; however, its molecular mechanism remains unclear. This study aimed to identify and experimentally validate the major active ingredients and prospective targets of FFGL.MethodsNetwork pharmacology, transcriptomics, and enrichment analysis were used to identify the active ingredients and prospective targets of FFGL, which were confirmed through subsequent experimental validation using mass spectrometry, molecular docking, western blotting, and in vitro assays.ResultsThe network pharmacology analysis revealed that FFGL contains a total of 78 active compounds, which led to the screening of 610 compound-related targets. Among them, 59 overlapped with CA targets and were considered to be targets with potential therapeutic effects. The protein-protein interaction network analysis revealed that protein kinase B (Akt) serine/threonine kinase 1 was a potential therapeutic target. To further confirm this result, we performed ribonucleic acid sequencing (RNA-seq) assays on HPV 18+ cells after FFGL exposure and conducted enrichment analyses on the differentially expressed genes that were screened. The enrichment analysis results indicated that the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway may be a key pathway through which FFGL exerts its effects. Further in vitro experiments revealed that FFGL significantly inhibited the activity of HPV 18+ cells and reduced PI3K and Akt protein levels. A rescue experiment indicated that the reduction in cell viability induced by FFGL was partially restored after the administration of activators of the PI3K/Akt pathway. We further screened two active components of FFCL that may be efficacious in the treatment of CA: periplogenin and periplocymarin. The molecular docking experiments showed that these two compounds exhibited good binding activity to Akt1.ConclusionFFGL reduced HPV 18+ cell viability by inhibiting key proteins in the PI3K/Akt pathway; this pathway may represent an essential mechanism through which FFGL treats CA. Periplogenin and periplocymarin may play a significant role in this process.
Project description:A 58-year-old male patient presented with an anorectal verrucous carcinoma, also known as Buschke-Lowenstein tumor. Clinically, the lesion of the patient best resembled giant condyloma acuminatum with a cauliflower-like appearance. The diagnosis was confirmed with biopsy and an abdominoperineal resection was performed. The perineal defect was reconstructed with bilateral gluteal musculocutaneous V-Y advancement flap. Both functional and cosmetic results 6 years after the operation were excellent. To date, no recurrence has been noted. As long as one is aware of its existence and of its characteristic appearances, the Buschke-Lowenstein tumor is fairly easily diagnosed. The treatment of choice remains surgical resection, and adequate follow-up is essential.
Project description:Condyloma acuminata (CA), or genital warts, are benign proliferative epidermal or mucous lesions that are caused by infection with human papillomavirus (HPV), mainly the low-risk types 6 and 11. HPV variants are defined as viral sequences that share identity in the nucleotide sequence of the L1 gene greater than 98%. Based on this criterion, HPV6 and 11 variant lineages have been studied, and there are ongoing attempts to correlate these genetic variants with different clinical findings of infection. Therefore, the aims of this study were to detect variants and nucleotide alterations present in the E6 regions of HPV types 6 and 11 found in CA samples, to correlate the HPV presence with the clinical-pathological data of the patients, and to determine phylogenetic relationships with variants from other places in the world. The E6 regions of 25 HPV6 samples and 7 HPV11 samples from CA were amplified using PCR with specific primers. The products were ligated to a cloning vector and five colonies of each sample were sequenced to observe the nucleotide alterations. Twelve samples were identified as the HPV6B3 variant, presenting the mutation (guanine) G474A (adenine), and one of them also showed the mutation (thymine) T369G. The other 13 patients were positive for HPV6B1 without nucleotide alterations. In the analysis of the HPV11 samples, all patients showed the mutations T137C and (cytosine) C380T. One patient also presented the nucleotide alteration T410C. None of the mutations found in the 32 analyzed samples resulted in amino acid changes. Patient age, local occurrence, and HIV infection did not show significant association with HPV infection. Besides, the data found in this study did not show a relationship with the geographical region of isolation when compared to other data from different regions of the world. In this way, despite the nucleotide alterations found, it was not possible to observe amino acid changes and variants grouping according to geographical region.
Project description:the assay was performed on 5 ug of total RNA samples from HPV negative foreskin tissues and HPV-6b positive CA specimen. The small RNAs were 3'-extended with a polyadenylate tail using polyadenylate (poly (A) polymerase and then ligated to an oligonucleot
Project description:Condyloma acuminatum is a sexually transmitted disease characterized by the anomalous proliferation of keratinocytes caused by human papillomavirus (HPV) infection. Fu Fang Gang Liu liquid (FFGL) is an effective external prescription to treat condyloma acuminatum, but its potential molecular mechanism is still unclear. This study aimed to identify the major active ingredients and prospective targets of FFGL by using network pharmacology, molecular docking, and transcriptomics, and validating it experimentally. Network pharmacology analysis found that FFGL contains a total of 78 active compounds, from which 610 compound-related targets were screened. Among them, 59 compound-related targets overlapped with CA targets and were considered as targets with potential therapeutic effects. Protein-protein network analysis showed that AKT serine/threonine kinase 1 was the potential therapeutic target. To further confirm this result we performed RNA-seq assays on HPV18+ cells after FFGL intervention, and conducted enrichment analyses on the screened differentially expressed genes. Enrichment analyses results indicated that the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway may be a key pathway for FFGL to function. Further in vitro experiments revealed that FFGL significantly inhibited the activity of HPV18+ cells and reduced PI3K and Akt protein levels. Rescue experiment indicated that the reduction in cell viability caused by FFGL was partially restored after the use of activators of the PI3K/Akt pathway. We further explored the active components of FFCL for the treatment of condyloma acuminatum and screened two active compounds, periplogenin and periplocymarin. Molecular docking showed that these two compounds have good binding activity to AKT1.
Project description:Expression profiling of HeLa cells transduced stably with pre-miR-31 mimic, miR-31 inhibitor and parental HeLa cells was performed using Human Whole Genome OneArray v6.1 (Phalanx Biotech Group, Taiwan, China). Four hybridizations for each group were performed, with two biological and two technical replicates. Briefly, the signal intensity of each spot was loaded into the Rosetta Resolver System (Rosetta Biosoftware, Cambridge, MA, USA) for data analysis. The technical repeat data were tested by Pearson's correlation coefficient calculation to check the reproducibility (R>0.95). Normalized spot intensities were transformed to gene expression log2 ratios between the control and treatment groups.