OBJECTIVE: To observe the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) for the treatment of erosive oral lichen planus (EOLP). METHODS: Sixty patients with clinically and pathologically diagnosed EOLP were randomly divided into the experimental group and control group according to the random number. Patients in the experimental group were treated with lyophilized powder containing Nr-CWS combined with normal saline. Patients in the control group received topical placebo without Nr-CWS combined with normal saline. Changes in the EOLP lesion area and the patient's pain level were recorded at the timepoints of weeks 1, 2, and 4 after the two different treatments, respectively. The changes of the patient's REU scoring system (reticulation, erythema, ulceration), the visual analogue scale and the oral health impact score (OHIP-14) were compared between the experimental group and control group after treatment, and the safety indicators of the two groups at the initial diagnosis and after 4 weeks' treatment were also observed, respectively. RESULTS: Totally, 62 patients with clinically and pathologically diagnosed EOLP were enrolled, 2 of whom were lost to the follow-up, with 31 in the experimental group, and 29 in the control group. The mean age of the experimental group and control group were (52.9±12.4) years and (54.07±12.40) years, respectively. There was no significant difference in the oral periodontal index between the experimental group and control group. In the experimental group, the erosive area of oral lichen planus was significantly reduced 1, 2, and 4 weeks after the Nr-CWS's treatment (P < 0.05), the reduction rate was 81.75%, the patient's pain index was also decreased (P < 0.05), and in addition, the OHIP-14 was reduced (P < 0.05). The changes of the REU scoring system, the visual analogue scale and the OHIP-14 were significantly different between the experimental group and control group after treatment. There was no significant difference in the safety index between the two groups. CONCLUSION The priliminary data show that the Nr-CWS is effective and safe to treat EOLP.
Adult ; Aged ; Cell Wall Skeleton ; Humans ; Lichen Planus, Oral/drug therapy* ; Middle Aged ; Pain Measurement ; Rhodococcus

Although intravesical instillation of Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most successful cancer immunotherapy for superficial bladder cancer, the serious side effects are frequently arisen by using live mycobacteria. To allow less toxic and more potent immunotherapeutic agents following intravesical BCG treatment for superficial bladder cancer, noninfectious immunotherapeutic drug instead of live BCG would be highly desirable. Recently, immune-enhancing adjuvants are considered an effective vaccine immunotherapy for cancer, providing enhanced antitumor effects and boosted immunity. The BCG-cell wall skeleton (BCG-CWS), the main immune active center of BCG, is a potent candidate as a noninfectious immunotherapeutic drug instead of live BCG against bladder cancer. However, the most limited application for anticancer therapy, it is difficult to formulate a water-soluble BCG-CWS due to the aggregation of BCG-CWS in both aqueous and nonaqueous solvents. To overcome the insolubility and improve the internalization of BCG-CWS into bladder cancer cells, it should be developed the lipid nanoparticulation of BCG-CWS, resulting in improved dispensability, stability, and small size. In addition, powerful technology of delivery systems should be applied to enhance the internalization of BCG-CWS, such as encapsulated into lipid nanoparticles using novel packaging methods. Here, we describe the progress in research on effects of BCG-CWS for cancer immunotherapy, development of lipid-based solvent, and packaging method using nanoparticles with drug delivery system.
Administration, Intravesical ; Bacillus ; Cell Wall Skeleton ; Drug Delivery Systems ; Immunotherapy ; Methods ; Mycobacterium bovis ; Nanoparticles ; Product Packaging ; Skeleton ; Solvents ; Urinary Bladder Neoplasms ; Urinary Bladder

Adjuvants, Immunologic ; therapeutic use ; Animals ; Carbon Tetrachloride ; Carbon Tetrachloride Poisoning ; Cell Wall Skeleton ; Chemical and Drug Induced Liver Injury ; therapy ; Male ; Mice

Chitin and chitosan, polysaccharides made up of polymeric N-acetly glucosamine and D-glucosamine, are widely found in nature, forming the skeletons of crustaceans and insects, as well as the components of bacteria cell walls. Chitin and chitosan have been known to have many useful biological properties such as biocompatibility, biodegradability, antimicrobial activity, and wound healing. There properties have been known to be different depending on the degree of deacetylation of chitin, but it has not yet been fully evaluated. The purpose of this study was to evaluate the wound healing effect by the degree of deacetylation. Full-thickness skin incision was made on the backs of Sprague-Dawley rats. Three concentrations of powder, comprising 90% chitin, 50% chitin and 10% chitin, were separately embedded in the wounds of 3 rat groups. The wound-breaking strength and the collagen-hydroxyproline content of the skin at the wound sites were measured and histological examination was performed at postoperative 3, 7, and 10 days. The 50% chitin group had the highest tensile strenght of all groups. But the 50% chitin and 90% chitin groups had the lowest collagen hydroxyproline levels among all groups. The wounds treated with 50% chitin powder were completely reepithelialized and granulation tissue in the wound was observed 7 days after initial wounding. The arrangement of collagen fibers in the skin was ordered and similar to normal skin The 50% chitin powder is considered to be the most efficient wound healing accelerator among different concentrations of chitin powder.
Animals ; Bacteria ; Cell Wall ; Chitin* ; Chitosan* ; Collagen ; Glucosamine ; Granulation Tissue ; Hydroxyproline ; Insects ; Polymers ; Polysaccharides ; Rats* ; Rats, Sprague-Dawley ; Skeleton ; Skin ; Wound Healing* ; Wounds and Injuries*

The effect of water soluble chitin on wound healing in rats Chitin and chitosan, polysaccharides made up of polymeric N-acetyl glucosamine and D-glucosamine, are widely found in nature, forming skeletons of crustaceans and insects as well as components of bacteria cell walls. Chitin and chitosan have been known to have many useful biological properties such as biocompatibility, biodegradability, antimicrobial activity, and wound healing property. The key-point of practical use of chitin was making water soluble form. The purpose of this study was to compare the wound healing effect of water soluble with insoluble chitin. Full-thickness skin incision was made on the backs of the Sprague-Dawley rats. Three groups composed respectively with saline, water insoluble chitin and water soluble chitin were embedded in the wounds. The wound breaking strength and the collagen-hydroxyproline content of the wounded skins were measured and histological examination was performed at the time of 3, 7, 10 days respectively after the procedure. The tensile strength was maximum in case of water soluble chitin. The amount of collagen hydroxyproline was minimum in water soluble chitin. The wound treated with the water soluble and insoluble chitin was completely reepithelialized and granulation tissue in the wound was observed at 7 days after initial wounding. The arrangement of collagen fibers in the skin was orderly and similar to normal skin.
Animals ; Bacteria ; Cell Wall ; Chitin* ; Chitosan ; Collagen ; Glucosamine ; Granulation Tissue ; Hydroxyproline ; Insects ; Polymers ; Polysaccharides ; Rats* ; Rats, Sprague-Dawley ; Skeleton ; Skin ; Tensile Strength ; Wound Healing* ; Wounds and Injuries*

Mesenchymal stem cell (MSC)-derived exosomes (Exos) were reported to a prospective candidate in accelerating diabetic wound healing due to their pro-angiogenic effect. MSCs pretreated with chemistry or biology factors were reported to advance the biological activities of MSC-derived exosomes. Hence, this study was designed to explore whether exosomes derived from human umbilical cord MSCs (hucMSCs) preconditioned with Nocardia rubra cell wall skeleton (Nr-CWS) exhibited superior proangiogenic effect on diabetic wound repair and its underlying molecular mechanisms. The results showed that Nr-CWS-Exos facilitated the proliferation, migration and tube formation of endothelial cells in vitro. In vivo, Nr-CWS-Exos exerted great effect on advancing wound healing by facilitating the angiogenesis of wound tissues compared with Exos. Furthermore, the expression of circIARS1 increased after HUVECs were treated with Nr-CWS-Exos. CircIARS1 promoted the pro-angiogenic effects of Nr-CWS-Exos on endothelial cellsvia the miR-4782-5p/VEGFA axis. Taken together, those data reveal that exosomes derived from Nr-CWS-pretreated MSCs might serve as an underlying strategy for diabetic wound treatment through advancing the biological function of endothelial cells via the circIARS1/miR-4782-5p/VEGFA axis.
Humans ; Endothelial Cells/metabolism* ; Exosomes/metabolism* ; Cell Wall Skeleton/metabolism* ; Neovascularization, Physiologic ; Wound Healing/physiology* ; MicroRNAs/metabolism* ; Diabetes Mellitus ; Vascular Endothelial Growth Factor A/metabolism*

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ²=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ²=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.
Female ; Humans ; Adult ; Middle Aged ; Cervix Uteri/pathology* ; Uterine Cervical Neoplasms/pathology* ; Papillomavirus Infections/diagnosis* ; Cell Wall Skeleton ; Persistent Infection ; Powders ; Uterine Cervical Dysplasia/pathology* ; Immunotherapy ; Papillomaviridae

OBJECTIVETo detect the effect of Nocardia rubra cell wall skeleton (Nr-CWS) on tumorigenicity induced by TC-1 cells and to clinically study anti-human papillomavirus effect of Nr-CWS in lower genital tract of women.

METHODSTumor model was established by injecting TC-1 cells subcutaneously in SCID mice, then divided them into 3 groups randomly and injected with isovolumetric physiological saline, 60 micrograms/ml Nr-CWS and 120 micrograms/ml Nr-CWS respectively, the growth of tumors was measured one week later. Nr-CWS was applied on 45 HPV positive women whose TCT test was normal and without cervical erosion 2-3 days after menstruation. HPV was detected again 3 months later to explore the effect of Nr-CWS on HPV infection in female lower genital tract.

RESULTSThe animal experiment showed the weight of transplanted tumors in treated group was less than that of control group (chi2=12.5, P= 0.002). The tumor inhibition rate was 59.1 percent and 84.2 percent in the groups treated with Nr-CWS 60 and 120 micrograms/ml Nr-CWS; the results of HPV detection in 23 out of the 45 cases (51.1 percent) became negative after the 3-month treatment; the viral load was reduced in 9, and there was no change in viral load in 13 cases. Significant difference was found between the rates of undetectable viral load and the natural viral disappearance rate (P less than 0.05).

CONCLUSIONNr-CWS has an inhibitory effect to TC-1 cell tumorigenesis and clinical application of Nr-CWS may eliminate the HPV infection in lower genital tract of a considerable proportion of women with HPV infection.

Adult ; Animals ; Cell Wall Skeleton ; therapeutic use ; Cervix Uteri ; virology ; DNA, Viral ; analysis ; Female ; Humans ; Mice ; Mice, SCID ; Middle Aged ; Papillomavirus Infections ; complications ; drug therapy ; Uterine Cervical Neoplasms ; drug therapy ; virology ; Viral Load

OBJECTIVETo investigate the effects of Nocardia rubra cell wall skeleton (Nr-CWS) on the HeLa cell line, one of the cell lines of human cervical cancer, infected with HPV.

METHODSHPV-infected HeLa (HPV 18-positive cells) cultured in vitro were divided into two groups: the experiment group and control group. Nr-CWS was added to the experiment group and PBS to the control. The growth and proliferation of HeLa cells were detected with MTT and flow cytometry technology. Inhibitive effect of HeLa transplanted tumor was investigated in Scid mice.

RESULTSThe growth of HeLa cells in the experimental group was apparently decreased compared with that of the control. The results of flow cytometry demonstrated that more HeLa cells were transferred into quiescent phase in the experimental group than that in the control. While less in the proliferative phase, both of the volume and weight of HeLa transplanted tumor with drug-added group were less than those of control group.

CONCLUSIONThe Nocardia rubra cell wall skeleton is a potiental growth inhibitor and inducer of apoptosis of cervical cancer cells in vitro and may provide a new way in prevention or supplementary management of anti-human papilloma virus.

Animals ; Cell Growth Processes ; drug effects ; Cell Survival ; drug effects ; Cell Wall Skeleton ; pharmacology ; therapeutic use ; Female ; Flow Cytometry ; HeLa Cells ; Host-Pathogen Interactions ; Humans ; Mice ; Mice, SCID ; Nocardia ; metabolism ; Papillomaviridae ; physiology ; Uterine Cervical Neoplasms ; pathology ; prevention & control ; virology ; Xenograft Model Antitumor Assays