Green Synthesis of Silver Nanoparticles Using the Plant Extracts of Vitex Agnus Castus L: An Ecofriendly Approach to Overcome Antibiotic Resistance.

Background: These days, silver nanoparticles (Ag NPs) have been given considerable attention and applied in medical technology due to their great antimicrobial and antioxidant features. In the present study, we aimed to synthesize Ag NPs through the reduction of silver nitrate in the presence of Vitex agnus castus L fruit extract. Methods: After collecting fruits, their extract was prepared and added to Ag NO3 to produce Ag NPs. The effect of different parameters like AgNO3 concentration (0.5, 1, 3, and 5 mM), sunlight exposure, and sunlight irradiation time (10, 20, 30, and 40 min) was investigated in the synthesis of Ag NPs. The features of Ag NPs were characterized using UV-visible spectroscopy, scanning electron microscope (SEM), X-ray diffraction (XRD) analysis, and dynamic light scattering analysis. Moreover, antimicrobial function of Ag NPs was evaluated using Escherichia coli and Bacillus cereus bacteria species and minimal inhibitory concentration (MIC) of Ag NPs against these two pathogens was measured. Results: The results showed that the synthesized nanoparticles had a spherical shape and the range size of 30-60 nm. For the first time, the antimicrobial activity of synthesized Ag NPs of Vitex agnus castus L fruit extract was shown. Conclusions: It can be stated that the biosynthesis of Ag NPs using fruit extract of this plant is an environmentally friendly, economic and harmless method without any use of poisonous substances and no side effects. These Ag NPs can be considered as suitable antibacterial agents and replacements for antibiotics.

The concordance between wide-area transepithelial sampling with computer-assisted 3-dimensional analysis (WATS-3D) and standard endoscope biopsy in the detection of Barrett's esophagus and esophageal dysplasia.

INTRODUCTION: Barrett's esophagus (BE) is a premalignant condition that leads to susceptibility to developing adenocarcinoma. The most common endoscopic surveillance technique is forceps biopsy, which involves sampling the specimen every 1 to 2 cm along the length of the lesion. This technique has a low sensitivity and often leaves the majority of the esophageal mucosa untested. Recently, the use of wide-area transepithelial sampling with computer-assisted 3-dimensional analysis (WATS-3D) has received much attention. However, there is little known about this novel technique, and this research aims to add to our knowledge of WATS-3D by comparing it to traditional forceps biopsy. MATERIALS AND METHODS: A retrospective observational study was performed. All existing GI biopsy cases diagnosed with WATS-3D were identified from the institutional pathology databases of NYU Langone Hospital - Long Island from 2019 to 2021. Data collection included patients' age, sex, and dysplasia results. Existing pathology reports and CDx diagnostics were reviewed. All the existing slides of the biopsy cases were pulled out and reviewed. Dysplasia was classified as no dysplasia, indefinite for dysplasia, lowgrade dysplasia, and high-grade dysplasia. RESULTS: A total of 109 cases were included in this study. There are 59 cases diagnosed as BE with forceps biopsy, 72 cases by WATS-3D, and 77 cases by WATS-3D combined with forceps biopsy. The sensitivity of detecting BE was significantly increased by WATS-3D and further by WATS-3D combined with forceps biopsy. In 59 cases diagnosed as BE with forceps biopsy, 50 cases were classified as no dysplasia, 3 cases were indefinite for dysplasia, 5 cases were low-grade dysplasia, and 1 case was high-grade dysplasia. In 72 cases diagnosed as BE by WATS-3D, 64 cases were classified as no dysplasia, 7 cases were indefinite for dysplasia, 1 case was high-grade dysplasia, and no cases with low-grade dysplasia. In 77 cases diagnosed as BE by WATS-3D combined with forceps biopsy, 63 cases were classified as no dysplasia, 8 cases were indefinite for dysplasia, 5 cases with low-grade dysplasia, and 1 case was highgrade dysplasia. The maximal longitudinal extent of the esophageal mucosal changes strongly correlated with the severity of BE. CONCLUSION: Compared to traditional forceps biopsy, WATS-3D was more sensitive in finding intestinal metaplasia. However, WATS-3D could not clearly discriminate low-grade dysplasia from indefinite for dysplasia and tended to classify low-grade dysplasia as indefinite for dysplasia. The addition of WATS-3D to forceps biopsy resulted in an increase in diagnostic yield and thus an increase in the quality of patient care.

Antibody Fragment and Targeted Colorectal Cancer Therapy: A Global Systematic Review.

BACKGROUND AND AIMS: Antibody-based therapeutics have been shown to be promising for the treatment of colorectal cancer patients. However, the size and long-circulating half-lives of antibodies can limit their reproducible manufacture in clinical studies. Consequently, in novel therapeutic approaches, conventional antibodies are minimized and engineered to produce fragments like Fab, scFv, nanobody, bifunctional antibody, bispecific antibody, minibody, and diabody to preserve their high affinity and specificity to target pharmaceutical nanoparticle conjugates. This systematic review for the first time aimed to elucidate the role of various antibody fragments in colorectal cancer treatment. METHODS: A systematic literature search in the web of sciences, PubMed, Scopus, Google Scholar, and ProQuest was conducted. Reference lists of the articles were reviewed to identify the relevant papers. The full-text search included articles published in English during 19902021. RESULTS: Most of the 53 included studies were conducted in vitro and in most conducted studies singlechain antibodies were among the most used antibody fragments. Most antibodies targeted CEA in the treatment of colorectal cancer. Moreover, a large number of studies observed apoptosis induction and tumor growth inhibition. In addition, few studies implicated the role of the innate immune system as an indirect mechanism of tumor growth by enhancing NK-cell killing. CONCLUSION: Antibody-based therapy was demonstrated to be of great promise in the treatment of colorectal cancer rather than common treatments such as radiotherapy, chemotherapy, and surgical operations. This type of specified cancer treatment can also induce the activation of the innate and specific immune systems to eradicate tumor cells.

Blockade of HIF-1α and STAT3 by hyaluronate-conjugated TAT-chitosan-SPION nanoparticles loaded with siRNA molecules prevents tumor growth.

HIF-1α and STAT3 are two of the critical factors in the growth, proliferation, and metastasis of cancer cells and play a crucial role in inhibiting anti-cancer immune responses. Therefore, we used superparamagnetic iron oxide (SPION) nanoparticles (NPs) coated with thiolated chitosan (ChT) and trimethyl chitosan (TMC) and functionalized with hyaluronate (H) and TAT peptide for delivery of siRNA molecules against STAT3 and HIF-1α to cancer cells both in vivo and in vitro. The results indicated that tumor cell transfection with siRNA-encapsulated NPs robustly inhibited proliferation and migration and induced apoptosis in tumor cells. Furthermore, simultaneous silencing of HIF-1α and STAT3 significantly repressed cancer development in two different tumor types (4T1 breast cancer and CT26 colon cancer) which were associated with upregulation of cytotoxic T lymphocytes and IFN-γ secretion. The findings suggest inhibiting the HIF-1α/STAT3 axis by SPION-TMC-ChT-TAT-H NPs as an effective way to treat cancer.

Recent developments in antibody derivatives against colorectal cancer; A review.

Colorectal cancer (CRC) is the fourth most common cause of cancer and mortality worldwide and is the third most common cancer in men and women. Surgery, radiotherapy, and chemotherapy are conventionally used for the treatment of colorectal cancer. However, these methods are associated with various side effects on normal cells. Thus, new studies are moving towards more effective and non-invasive methods for treatment of colorectal cancer. Targeted therapy of CRC is a promising new approach to enhance the efficiency and decrease the toxicity of the treatment. In targeted therapy of CRC, antibody fragments can directly inhibit tumor cell growth and proliferation. They also can act as an ideal carrier for targeted delivery of anticancer drugs. In the present study, the structure and function of different formats of antibody fragments, immune-targeted therapy of CRC using antibody fragments will be discussed.

Pathological findings in the postmortem liver of patients with coronavirus disease 2019 (COVID-19).

Although coronavirus disease 2019 (COVID-19) is transmitted via respiratory droplets, there are multiple gastrointestinal and hepatic manifestations of the disease, including abnormal liver-associated enzymes. However, there are not many published articles on the pathological findings in the liver of patients with COVID-19. We collected the clinical data from 17 autopsy cases of patients with COVID-19 including age, sex, Body mass index (BMI), liver function test (alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), direct bilirubin, and total bilirubin), D-dimer, and anticoagulation treatment. We examined histopathologic findings in postmortem hepatic tissue, immunohistochemical (IHC) staining with antibody against COVID-19 spike protein, CD68 and CD61, and electron microscopy. We counted the number of megakaryocytes in liver sections from these COVID-19-positive cases. Abnormal liver-associated enzymes were observed in 12 of 17 cases of COVID-19 infection. With the exception of three cases that had not been tested for D-dimer, all 14 patients' D-dimer levels were increased, including the cases that received varied doses of anticoagulation treatment. Microscopically, the major findings were widespread platelet-fibrin microthrombi, steatosis, histiocytic hyperplasia in the portal tract, mild lobular inflammation, ischemic-type hepatic necrosis, and zone 3 hemorrhage. Rare megakaryocytes were found in sinusoids. COVID-19 IHC demonstrates positive staining of the histiocytes in the portal tract. Under electron microscopy, histiocyte proliferation is present in the portal tract containing lipid droplets, lysosomes, dilated ribosomal endoplasmic reticulum, microvesicular bodies, and coronavirus. The characteristic findings in the liver of patients with COVID-19 include numerous amounts of platelet-fibrin microthrombi, as well as various degrees of steatosis and histiocytic hyperplasia in the portal tract. Possible mechanisms are also discussed.

Cutaneous amyloidosis as the first presentation of Waldenstrom macroglobulinemia.

BACKGROUND: Waldenstrom macroglobulinemia is a lymphoplasmacytic lymphoma with elevated serum immunoglobulin M and multi-organ involvement. Primary systemic amyloidosis usually develops due to immunoglobulin light chains depositions in different organs due to an underlying gammopathy. CASE PRESENTATION: Our patient was an 86-year-old man with macroglossia, ecchymotic patches and bullous lesions associated with a skin laxity on the periorbital, palmar, and glans penis areas. Skin biopsy confirmed dermal amyloid depositions. In serum immunofixation electrophoresis, prominent monoclonal immunoglobulin-M lambda light chains were detected associated with prominent lymphoplasmacytic infiltration in bone marrow biopsy which was diagnosed as Waldenstrom macroglobulinemia. CONCLUSION: Skin involvement presenting as cutaneous amyloidosis could be the first manifestation of Waldenstrom macroglobulinemia. We should think about an underlying gammopathy in an old patient with skin laxity and ecchymosis.

Codelivery of HIF-1α siRNA and Dinaciclib by Carboxylated Graphene Oxide-Trimethyl Chitosan-Hyaluronate Nanoparticles Significantly Suppresses Cancer Cell Progression.

PURPOSE: Hypoxia-inducible factor (HIF) is one of the critical components of the tumor microenvironment that is involved in tumor development. HIF-1α functionally and physically interacts with CDK1, 2, and 5 and stimulates the cell cycle progression and Cyclin-Dependent Kinase (CDK) expression. Therefore, hypoxic tumor microenvironment and CDK overexpression lead to increased cell cycle progression and tumor expansion. Therefore, we decided to suppress cancer cell expansion by blocking HIF-1α and CDK molecules. METHODS: In the present study, we used the carboxylated graphene oxide (CGO) conjugated with trimethyl chitosan (TMC) and hyaluronate (HA) nanoparticles (NPs) loaded with HIF-1α-siRNA and Dinaciclib, the CDK inhibitor, for silencing HIF-1α and blockade of CDKs in CD44-expressing cancer cells and evaluated the impact of combination therapy on proliferation, metastasis, apoptosis, and tumor growth. RESULTS: The results indicated that the manufactured NPs had conceivable physicochemical properties, high cellular uptake, and low toxicity. Moreover, combination therapy of cancer cells using CGO-TMC-HA NPs loaded with HIF-1α siRNA and Dinaciclib (SCH 727965) significantly suppressed the CDKs/HIF-1α and consequently, decreased the proliferation, migration, angiogenesis, and colony formation in tumor cells. CONCLUSIONS: These results indicate the ability of CGO-TMC-HA NPs for dual drug/gene delivery in cancer treatment. Furthermore, the simultaneous inhibition of CDKs/HIF-1α can be considered as a novel anti-cancer treatment strategy; however, further research is needed to confirm this treatment in vivo. Graphical Abstract The suppression of HIF-1α and CDKs inhibits cancer growth. HIF-1α is overexpressed by the cells present in the tumor microenvironment. The hypoxic environment elevates mitochondrial ROS production and increases p38 MAP kinase, JAK/STAT, ERK, JNK, and Akt/PI3K signaling, resulting in cyclin accumulation and aberrant cell cycle progression. Furthermore, the overexpression of HIF-1α/CDK results in increased expression of genes such as BCL2, Bcl-xl, Ki-67, TGFß, VEGF, FGF, MMP2, MMP9, and, HIF-1α and consequently raise the survival, proliferation, angiogenesis, metastasis, and invasion of tumor cells. In conclusion, HIF-1α-siRNA/Dinaciclib-loaded CGO-TMC-HA NPs can inhibit the tumor expansion by blockage of CDKs and HIF-1α (JAK: Janus kinase, STAT: Signal transducer and activator of transcription, MAPK: mitogen-activated protein kinase, ERK: extracellular signal-regulated kinase, JNK: c-Jun N-terminal kinase, PI3K: phosphatidylinositol 3-kinase).

T-Cell Large Granular Lymphocyte Leukemia in a Patient With Rheumatoid Arthritis.

Large granular lymphocyte leukemia (LGL) is a clonal, lymphoproliferative disorder with an indolent disease course. T-cell LGL (T-LGL) is the most common type of LGL driven from T-cell lineage (85%). The coexistence of T-LGL with several types of autoimmune disorders, mostly rheumatoid arthritis (RA), has been reported. Felty's syndrome (FS) is defined by splenomegaly, low neutrophil count, and destructive arthritis and is usually seen in <1% of patients with RA. About 30% to 40% of patients with FS have been reported to have an expansion of large granulated lymphocytes in the circulation. FS and T-LGL are similar in terms of clinical manifestations, response to immunosuppressive therapy, their smoldering course, and immunogenetic findings, proposing FS and T-LGL with RA might be different aspects of a single disease spectrum. In this article, we present a case with long-standing RA who had never been on DMARD (Disease Modifying Anti-Rheumatic Drugs) treatment found to have constitutional symptoms, neutropenia, and splenomegaly, and the patient was diagnosed with T-LGL.

Unilateral eyelid edema and mucosal involvement as the first presentations of Wegener granulomatosis.

BACKGROUND: Wegener granulomatosis or granulomatosis with polyangiitis is a pauci-immune small vessel vasculitis which is usually associated with anti-neutrophil cytoplasmic antibodies (ANCA) mainly in old men. This small vessel vasculitis is usually characterized by necrotizing granulomatous inflammation with multiorgan involvement. Kidneys could be involved as the main and life-threatening condition in Wegener granulomatosis. Oral or ocular lesions may occur as the first and uncommon presentations before internal organ involvement in these patients and could be misdiagnosed with other diseases. CASE PRESENTATION: We present a 24-year-old man with erosions and ulcerations on palatal mucosa and a strawberry-like gingival hypertrophy associated with nasal congestion and epistaxis which two stated months ago. Also he had an episode of unilateral blepharitis and upper eyelid edema five months ago. Mucosal biopsy showed perivascular infiltrations of mainly neutrophils, some eosinophils and rare giant cells. He had elevated level of proteinase 3-ANCA or C-ANCA with microscopic hematuria without significant kidney involvement in kidney biopsy. Mucosal lesions and hematuria improved after two months of treatment with oral prednisolone. CONCLUSION: Unilateral eyelid edema and mucosal erosions in a young man could be the uncommon presentations of Wegener granulomatosis.

Evaluation of serum folate level before and after bath PUVA therapy in patients referred to Razi Hospital, Rasht, Iran.

Ultraviolet (UV) radiation could disintegrate folate molecule, so phototherapy may reduce folate levels in the patients. The effect of phototherapy on serum folate in human body is questionable. We investigated the effect of bath PUVA therapy on serum folate level. This study was designed as a before-after study. Thirty-two patients completed study during 2 years. Our variables were demographic data, folate levels before and 8 weeks after treatment and cumulative dosage of UVA during 8 weeks of treatment. Serum folate was evaluated with chemiluminescence immunoassay technique. All data were analyzed using SPSS 18 software. Folate level changes were statistically significant before and after bath PUVA therapy. There was no significant difference in folate levels in psoriasis patients compared with nonpsoriasis patients. In psoriasis patients, folate levels had no significant correlation with psoriasis activity index before treatment. Decrease in folate levels was more significant in fair-skinned patients. There was no association between folate status and cumulative dosage of UVA. Bath PUVA therapy reduced serum folate level in our patients although none of them were folate deficient. Folate deficiency should be evaluated and corrected especially in fair-skinned cases, as it may be aggravated by phototherapy.

Association between Immunofluorescence Pattern and Mucosal Involvement in Patients with Bullous Pemphigoid.

Bullous pemphigoid is an acquired autoimmune subepidermal blistering disease which is associated with mucocutaneous lesions. The type and amount of autoantibody deposition may have a role in mucosal lesions. We studied the association between mucosal involvement and direct immunofluorescence pattern in cutaneous lesions of patients with bullous pemphigoid. In this retrospective analytical cross-sectional study, we studied the demographic data, clinical presentations, and immunopathological findings of 69 patients with bullous pemphigoid admitted to our hospital 2008-2016. Patients were allocated into two groups on the basis of the mucosal involvement, and direct immunofluorescence patterns were evaluated. The data were analyzed using SPSS version18. The mean age of patients was 70.9±14.97 (mean ± Standard Deviation) years old. In our study, 56.5% of patients were women. All patients showed deposition of IgG and C3 in the dermoepidermal junction, with different severity. Patients with mucosal involvement (40.6% of cases) had a more prominent deposition of IgG, IgA, and C3 at the dermoepidermal junction compared with patients without mucosal involvement, which represented a statistically significant difference (P<0.05). Logistic regression analysis showed that lower age, IgA, and C3 deposition (P<0.05) were associated with mucosal involvement. Deposition of IgA and C3 (in addition to IgG) at the dermoepidermal junction seems to be a marker of mucosal involvement in patients with bullous pemphigoid. Attention to direct immunofluorescence pattern in patients with bullous pemphigoid may be helpful in prediction of mucosal involvement in these patients.

Evaluation of Lipid Profile in Patients with Cherry Angioma: A Case-Control Study in Guilan, Iran.

BACKGROUND: Cherry angioma is the most common type of acquired cutaneous vascular proliferation which would increase with aging due to some angiogenic factors but the exact pathogenesis is unknown. Usually angiogenic factors are synthesized in human body to compensate occlusive effects of atherogenic agents such as serum lipids. Our hypothesis was that increased levels of these angiogenic factors could be a trigger for development of cherry angioma. This study has been designed to compare frequency of dyslipidemia in subjects with and without cutaneous cherry angioma. METHODS: In this case-control study, 122 cases with cherry angioma and 122 control subjects without cherry angioma were enrolled. Demographic characteristics, number of the cherry angioma lesions, and serum lipid profile were collected for all subjects. The data was analyzed using SPSS 18 software. RESULTS: Mean levels of the total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein were higher in patients with cherry angioma compared to control subjects in which differences were significant for total cholesterol, low-density lipoprotein, and triglyceride (P < 0.05) but not for high-density lipoprotein level. CONCLUSION: Serum lipids may have a role in producing angiogenic factors and development of cherry angioma and it seems logical to evaluate lipid profile in these cases.

Extramammary Paget's Disease Associated With Genital Wart and Lichen Sclerosus.

Extramammary Paget's disease is an uncommon intraepithelial adenocarcinoma in genital and perianal regions. Genital wart is the most common sexually transmitted disease caused by human papilloma viruses and vulval lichen sclerosus is chronic pruritic dermatitis in genital area which could be able to change to invasive squamous cell carcinoma. We report a patient who had simultaneous lichen sclerosus, genital wart and extramammary Paget's disease of the vulva. We could not find any significant association between them in literature.

Discoid Lupus Erythematosus Presenting as Upper Eyelid Edema and Erythema.

Discoid Lupus Erythematosus (DLE) is an autoimmune disorder that usually occurs on sun exposed areas of head and neck. Infrequently it could be presented by palpebral involvement and rarely unilateral upper eye lid edema and erythema have been reported as the sole manifestation of DLE. We describe a 38-year-old woman with chronic left upper eye lid edema and erythema from one year ago which was induced by steroid injection for left eyebrow alopecia. Histopathologic and direct immunofluorescent studies were made on palpebral skin tissue and confirmed DLE diagnosis. Antinuclear antibody (ANA) titer was 1/160 with speckled pattern. She was treated by oral hydroxychloroquine (400 mg daily) with moderate improvement after three months. We should think about DLE in cases with chronic upper eye lid edema and erythema. The aim of this case report is to emphasize that ophthalmologist and dermatologists should be aware of different presentations of DLE in the periorbital area to prevent misdiagnosis.