"Decoding inflammation: glycoprotein a repetition predominant, microRNA-142-3-p, and metastasis associated lung adenocarcinoma transcript 1: as novel inflammatory biomarkers of inflammatory bowel disease".

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic gastrointestinal (GI) condition comprising Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis involves immune system dysregulation, with increased Th (T helper cell)17 cells and reduced regulatory T cell (Treg) differentiation. Transforming growth factor-ß (TGF-ß) secretion from Tregs helps control inflammation, and its production is regulated by glycoprotein-A repetition predominant (GARP) protein along with non-coding RNAs (ncRNAs) like microRNA(miR)-142-3p and metastasis associated lung adenocarcinoma transcript 1 (MALAT1) long non-coding RNAs (LncRNAs). This study analyzed their expression in IBD. METHODS: Blood samples were collected from 44 IBD patients, and 22 healthy controls (HC). RNA extraction and circular DNA (cDNA) synthesis were performed. Real-time polymerase chain reaction (RT-PCR) measured gene expression of GARP, MALAT1, and miR-142-3p. Correlations and group differences were statistically analyzed. RESULTS: Compared to controls, GARP was downregulated while MALAT1 and miR-142-3p were upregulated significantly in IBD group. GARP and MALAT1 expressions positively correlated in controls. MALAT1 and miR-142-3p expressions positively correlated in IBD group. MALAT1 was downregulated in aged HC but upregulated with smoking history across groups. No correlations occurred between gene expression and gender, diet, infections, or disease activity scores. CONCLUSIONS: Dysregulation of GARP, MALAT1, and miR-142-3p likely contributes to inflammation in IBD by reducing TGF-ß. MALAT1 is linked to smoking and age-related changes. These genes have potential as diagnostic markers or therapeutic targets for personalized IBD treatment.

99mTc(CO)3-labeled 1-(2-Pyridyl)piperazine derivatives as radioligands for 5-HT7 receptors.

BACKGROUND: The 5-hydroxytryptamine receptor (5-HTR) family includes seven classes of receptors. The 5-HT7R is the newest member of this family and contributes to different physiological and pathological processes. As a pathology, glioblastoma multiform (GBM) overexpresses 5-HT7R; hence, this study aims to develop radiolabeled aryl piperazine derivatives as 5-HT7R imaging agents.  METHODS: Compounds 6 and 7 as 1-(3-nitropyridin-2-yl)piperazine derivatives were radiolabeled with fac-[99mTc(CO)3(H2O)3]+ and 99mTc(CO)3-[6] and 99mTc(CO)3-[7] were obtained with high radiochemical purity (RCP > 94%). The stability of the radiotracers was evaluated in both saline and mouse serum. Specific binding on different cell lines including U-87 MG, MCF-7, SKBR3, and HT-29 was performed. The biodistribution of these radiotracers was evaluated in normal and U-87 MG Xenografted models. Finally, 99mTc(CO)3-[6] and 99mTc(CO)3-[7] were applied for in vivo imaging in U-87 MG Xenografted models. RESULTS: Specific binding study indicates that 99mTc(CO)3-[6] and 99mTc(CO)3-[7] can recognize 5-HT7R of U87-MG cell line. The biodistribution study in normal mice indicates that the brain uptake of 99mTc(CO)3-[6] and 99mTc(CO)3-[7] is the highest at 30 min post-injection (0.8 ± 0.25 and 0.64 ± 0.18%ID/g, respectively). The data of the biodistribution study in the U87-MG xenograft model revealed that these radiotracers could accumulate in the tumor site, and the highest tumor uptake was observed at 60 min post-injection (3.38 ± 0.65 and 3.27 ± 0.5%ID/g, respectively). The injection of pimozide can block the tumor's radiotracer uptake, indicating the binding of these radiotracers to the 5-HT7R. The imaging study in the xenograft model also confirms the biodistribution data. The acquired images clearly show the tumor site, and the tumor-to-muscle ratio for 99mTc(CO)3-[6] and 99mTc(CO)3-[7] at 60 min was 3.33 and 3.88, respectively.  CONCLUSIONS: 99mTc(CO)3-[6] and 99mTc(CO)3-[7] can visualize tumor in the U87-MG xenograft model  due to their affinity toward 5-HT7R.

Evaluation of myocardial viability by a secondary delayed 99mTc-MIBI nuclear scanning in ST-elevation myocardial infarction patients with delay in referral and nonviable myocardium in the first scintigraphy: a preliminary cohort study.

OBJECTIVE: In the management of ST-segment elevation myocardial infarction (STEMI), if the treatment has not been initiated within the first 24 h and the patient no longer exhibits any symptoms, the decision to begin revascularization therapy is based on myocardial viability. If the tissue is nonviable, current guidelines advise against further revascularization therapy; however, collateral vessels represent an alternative source of blood supply and may help the damaged tissue to resume function; though at first, this tissue may not be considered viable. Thus, in patients whose first myocardial perfusion scintigraphy (MPS) revealed nonviable myocardium, a secondary MPS to assess viability may be beneficial and alter the course of treatment strategies. METHODS: This prospective cohort study was conducted on 30 STEMI patients referred to Mazandaran Heart Center. If no myocardial viability was found using 99mTc-MIBI MPS, the patient was referred for a secondary MPS after 3 months. RESULTS: In total, out of 30 patients, 3 became viable. There was no significant relationship between the viability of different Rentrop classes. Comparison of viability between patients with different numbers of occluded vessels showed no significant relationship. Three patients (17%) among 17 patients with Rentrop class nonzero became viable in the second MPS. Also, among four patients (13.3%) with Rentrop class three, one patient (25%) became viable and among seven patients (23.3%) with Rentrop class one, two patients (28.6%) became viable. CONCLUSION: Considering the results of this study, although nonsignificant, this subject requires further investigation to reach a definite conclusion.

The preclinical study of 177Lu-DOTA-LTVSPWY as a potential therapeutic agent against HER2 overexpressed cancer.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) has evolved in cancer therapy and diagnosis. LTVSPWY, as a peptide, can target HER2 receptor; on the other hand, 177Lu emits ß- which is helpful for cancer therapy. The radiolabeling of LTVSPWY with 177Lu results in a therapeutic agent (177Lu-DOTA-LTVSPWY) capable of cancer treatment. METHODS: 177Lu-DOTA-LTVSPWY was prepared with high radiochemical purity (RCP). The stability was investigated in saline and human serum. The radiotracer affinity toward the SKOV-3 cell line with overexpression of the HER2 receptor was evaluated. Then the impact of the radiotracer on the colony formation of the SKOV-3 cell line was investigated with colony assay. Moreover, the biodistribution of this radiotracer in SKOV-3 xenograft tumor-bearing nude mice were also studied to determine the radiotracer accumulation in the tumor site. The mice were treated with 177Lu-DOTA-LTVSPWY and subjected to histopathological evaluation. RESULTS: The RCP of 177Lu-DOTA-LTVSPWY after radiolabeling and stability tests was more than 97.7%. The radiotracer displayed high affinity toward the SKOV-3 cell line (KD = 6.6 ± 3.2 nM). Treatment of the SKOV-3 cell line with the radiotracer reduces the SKOV-3 colony survival to less than 3% for 5 MBq of the radiotracer. Tumor-to-muscle (T/M) ratio is the highest at 48 h and 1 h post-injection (2.3 and 4.75, respectively). The histopathological study also confirms the cellular damage to the tumor tissue. CONCLUSIONS: 177Lu-DOTA-LTVSPWY can recognize HER2 receptors in vivo and in vitro; hence, it can serve as a therapeutic agent.

Comparison of early surgical and conservative therapy in children with ureteropelvic junction obstruction.

BACKGROUND: Ureteropelvic junction obstruction is a relatively common urologic problem in children. Most cases present with pelvicaliceal dilatation in antenatal period. Historically most UPJO cases were treated with surgical procedures, but recently many of these children have been treated by nonsurgical observational plans. We compared the outcome of children with UPJO treated in surgical and observational ways. METHODS: In a retrospective study, we assessed the medical history of patients diagnosed as UPJO, march 2011 to march 2021. The case definition was based on grade 3-4 hydronephrosis and obstructive pattern in dynamic renal isotopes can. Patients were put into two groups; Group 1 children were treated with a surgical procedure, and group 2 patients without any surgical procedure for at least a six months' period after diagnosis. We assessed long-term events and improvement of obstruction. RESULTS: Seventy-eight children (mean age 7.32mo., 80% male) enrolled in the study, 55 patients in group one and 23 as group 2. Severe hydronephrosis was the problem of 96% of all patients significantly led to 20% in group 1 and 9% in group 2 (P < 0.001). Severe kidney involvement was observed at 91% in group 1 and 83% in group 2, decreased to 15% and 6%, respectively (P < 0.001). There were no significant differences in sonographic and functional improvement between the two intervention groups. Long-term prognostic issues; growth, functional impairment, and hypertension were not different between the two groups, but group 1 children experienced more recurrence of UTI than group 2 patients. CONCLUSION: Conservative management is as effective as early surgical treatment in the management of infants with severe UPJO.

Synthesis and evaluation of 99mTc-labeled 1-(2-Pyridyl)piperazine derivatives as radioligands for 5HT7 receptors.

Glioblastoma multiform (GBM) is one of the most aggressive tumors of the central nervous system in humans. GBM overexpresses serotonin-7 receptors (5-HT7Rs); hence, this study aims to develop 5-HT7R targeted radiotracers. Aryl piperazine derivatives can act as ligands for 5-HT7R. Therefore, compounds 6 and 7 as 1-(3-nitropyridin-2-yl)piperazine derivatives were synthesized and radiolabeled with 99mTcN2+ core. Radiolabeled 6 and 7 (99mTcN-[6] and 99mTcN-[7]) were prepared with high radiochemical purity (RCP > 96%). They displayed high affinity toward U-87 MG cell line 5-HT7R. The calculated Ki for 99mTcN-[7] was lower than that of 99mTcN-[6] (14.85 ± 0.32 vs 22.57 ± 0.73 nM) which indicates the higher affinity of 99mTcN-[7] toward 5-HT7R. A molecular docking study also confirmed the binding of these radiotracers to 5-HT7R. The biodistribution study in normal mice revealed that 99mTcN-[7] has the highest brain accumulation at 30 min post-injection (0.54 ± 0.12 %ID/g) while the uptake of 99mTcN-[6] is much lower (0.14 ± 0.02 %ID/g). The biodistribution study in the xenograft model confirms that the radiotracers recognize the tumor site. 99mTcN-[6], and 99mTcN-[7] showed the highest tumor uptake at 1-hour post-injection (5.44 ± 0.58 vs 4.94 ± 1.65 %ID/g) and tumor-to-muscle ratios were (4.61 vs. 5.61). The injection of pimozide blocks the receptors and significantly reduces the tumor-to-muscle ratios at 1-hour post-injection to 0.81 and 0.31, respectively. In correlation with in vitro study, 99mTcN-[6] and 99mTcN-[7] visualize the tumor site in U-87 MG glioma xenografted nude mice and display the tumor-to-muscle ratios of 7.05 and 6.03.

Melissa Officinalis L. aqueous extract pretreatment decreases methotrexate-induced hepatotoxicity at lower dose and increases 99mTc-phytate liver uptake, as a probe of liver toxicity assessment, in rats.

OBJECTIVE: Hepatotoxicity remains amongst the restricting factors of Methotrexate (MTX)-associated cancer therapy, especially in high doses of chemo-drugs or prolonged treatment. Due to the known protective effects of Melissa officinalis (M. officinalis), the aqueous extract of this plant was evaluated to ameliorate MTX-associated hepatotoxicity in rats. METHODS: Adult female Wistar rats were received or not M. officinalis aqueous extract at doses of 100 mg/kg (for 14 and 24 consecutive days) and 2 g/kg (for 14 consecutive days) by gavage technique. MTX (20 mg/kg) was intraperitoneally injected on the 10th- and 20th-day post-M. officinalis treatment. 24 h after the last day of treatment, 99mTc-phytate was intravenously injected through the tail of rats. Animals were killed at 20 min after radiocolloid injection, and vital tissues including the liver and spleen were isolated, weighed, and their radioactivity was counted. As well, 99mTc-phytate scintigraphy and histopathology of the liver were performed for higher accuracy. RESULT: A significant increase in liver radioactivity was detected in M. officinalis+MTX receiving groups compared with the MTX rats which were more robust at a dose of 100 mg/kg for 14 days. Also, a significant reduction in liver radioactivity was evident with M. officinalis extract at a dose of 2 g/kg for 14 days in comparison with the control group, this reduction was not significant at the lower dose of 100 mg/kg. Gamma scintigraphy and histopathological examinations confirmed the hepatoprotective effect of M. officinalis vs MTX-induced liver injury in rats. CONCLUSION: In conclusion, we highlighted the liver uptake of 99mTc-phytate as a valuable method for assessment of liver toxicity and addressed that M. officinalis pretreatment (100 mg/kg for 14 days) ameliorates the MTX-associated hepatotoxicity in rats; however, M. officinalis itself induces liver toxicity at higher doses.

Molecular Imaging of HER2 Expression in Breast Cancer patients Using the [99mTc] Tc-Labeled Small Peptide.

PURPOSE: The accurate determination of human epidermal growth factor receptor 2 (HER2) status can predict response to treatment with HER2-targeted therapy for HER2-positive breast cancer patients. [99mTc]Tc-HYNIC-(Ser)3-LTVPWY ([99mTc]Tc-HYNIC-LY) is a small synthetic peptide molecule targeting of the HER2 receptor. This clinical study evaluated the pharmacokinetic, dosimetry, and efficacy of [99mTc]Tc-HYNIC-LY for determining the HER2 status in primary breast cancer patients. MATERIALS AND METHODS: In total, 24 women with suspected primary breast cancer received an intravenous injection of approximately 20 µg (∼740 MBq) of [99mTc]Tc-HYNIC-LY. In the first 3 patients, blood levels of radioactivity were analyzed for pharmacokinetic evaluation and planar gamma camera imaging was conducted at 30 min and 1, 2, 4, and 24 hour after injection for dosimetry assessment. In the last 21 patients, planar imaging was performed at the baseline, as well as 1, 2, 3, and 4 hour, followed by single-photon emission computed tomography (SPECT) imaging after 4 hour to evaluate the tumor-targeting potential in primary lesions. RESULTS: Injection of [99mTc]Tc-HYNIC-LY was safe and well tolerated. Fast blood clearance provided high-contrast HER2 imaging within 1 to 4 hour. The highest absorbed radiation dose was found for kidneys (6.78E-03 ± 2.62E-04 mSv/MBq), followed by the heart (3.73E-03 ± 1.98E-04 mSv/MBq). The [99mTc]Tc-HYNIC-LY peptide was able to detect HER2 status in primary tumors at an acceptable level. CONCLUSION: The findings of this study indicated that [99mTc]Tc-HYNIC-LY SPECT is safe and feasible for the identification of HER2-positive lesions in primary breast cancer patients, and may provide an accurate and non-invasive modality for guiding HER2 targeted therapy.

Patient-related post-ERCP pancreatitis (PEP) risk factors between two groups of patients: Prophylactic pancreatic stent and rectal indomethacin.

Background: Pancreatitis is one of the most crucial complications following endoscopic retrograde cholangiopancreatography (ERCP). The purpose of the current study was to investigate patient-related post-ERCP pancreatitis (PEP) risk factors in two groups of patients: prophylactic pancreatic stent and rectal indomethacin. Methods: Two different prophylactic modalities were planned and complications were assessed based on the defined inclusion criteria. In this study, the patients were evaluated for the procedure and patient-related risk factors in post-ERCP pancreatitis in the recipient groups of the prophylactic pancreatic stent and rectal indomethacin. Results: Pancreatitis was confirmed in 27 of all 170 selected patients after ERCP. By univariate analysis, two variables were significant with the development of PEP. Regarding the patient-related risk factors, unique subjects with common bile duct (CBD) dilated 10mm were more exposed to an increased chance of PEP (P=0. 015); meanwhile, other factors did not correlate with the increased possibility of PEP in both groups. The only procedure-related risk factor for PEP was the deep cannulation of the pancreatic duct in both groups during the procedure with an incremental significant incidence of pancreatitis (P=0.005). Comparison of prophylactic pancreatic stent and rectal indomethacin showed no effects in term of post ERCP pancreatitis reduction. Additionally, there was no significant difference between these two strategies in the rate of PEP. Conclusion: Prophylactic pancreatic duct stents and administration of rectal indomethacin cannot have particular approaches for reducing the possible occurrence of PEP. The increase in time of deep cannulation and the presence of CBD dilation <10mm could be considered as important risk factors.

[99mTc]-labeling and evaluation of a new linear peptide for imaging of glioblastoma as a αvß3-positive tumor.

PURPOSE: In this study, we designed a new linear 6-Hydrazinonicotinamide (HYNIC)-conjugated peptide (HYNIC-KRWrNM) (M-6) and labeled with technetium-99m for gamma imaging of glioblastoma as a αvß3-positive tumor. We evaluated tumor targeting ability of this radio-peptide and compared with previous 99mTc-labeled HYNIC-conjugated RGD analogue peptides. PROCEDURES: One new linear peptide (HYNIC-KRWrNM) (M-6) was designed and labeled with technetium-99m in the presence of 2-[[1,3-dihydroxy-2-(hydroxymethyl) propan-2-yl] amino] acetic acid (Tricine)/Ethylenediamine-N,N'-diacetic acid (EDDA) as co-ligand system. Then, this 99mTc-labeled peptide ([99mTc]Tc-M-7) was evaluated for in vitro stability in saline and serum, specific binding assay, internalization, and binding affinity (Kd). In addition, we performed biodistribution study and planar imaging on nude mice bearing U87-MG xenograft as a αvß3-positive tumor. RESULTS: The radiochemical yield of [99mTc]Tc-M-7 was obtained ˃95%. This 99mTc-labeled peptide remained stable and intact in saline solution after 24 h incubation. In addition, metabolic stability of this 99mTc-labeled peptide was obtained ˃60% after 4 h incubation in serum. The Kd value for [99mTc]Tc-M-7 was obtained 5.2 ± 1.0 nM. Based on biodistribution results in nude mice bearing U87-MG xenograft, tumor/muscle activity ratio was 6.22 and decreased to 1.89 in blocking group at the same time point (4 h p.i.). The blocking experiment results also indicated that tumor uptake and kidney uptake were αvß3-mediated. In comparison with previous HYNIC-conjugated RGD analogue peptides, kidneys had the highest uptake of this 99mTc-labeled peptide (52.29 ± 11.48 at 1.5 h p.i. and 27.04 ± 0.66%ID/g at 4 h p.i.). Finally, similar to previous 99mTc-labeled HYNIC-conjugated RGD analogue peptides, [99mTc]Tc-M-7 showed acceptable tumor uptake after 4 h post-injection (based on ROI technique, target-to-background activity ratio = 3.80). CONCLUSIONS: This small linear 99mTc-labeled peptide, with high affinity to αvß3 integrin, desirable water solubility, and cost efficient, demonstrates a potent tumor targeting ability as well as previous HYNIC-conjugated RGD analogue peptides. Hence, [99mTc]Tc-M-7 can be of service to as a new candidate for early detection of αvß3-positive tumors.

Homodimer 99mTc-HYNIC-E(SSSLTVPWY)2 peptide improved HER2-overexpressed tumor targeting and imaging.

We hypothesized that a novel design of the LTVPWY (LY) peptide might exhibit a great potential for improving binding affinity and targeting HER2-overexpressed tumors. Hence, new dimer construction of 99mTc-labeled LY [99mTc-HYNIC-E(SSSLTVPWY)2] (99mTc-DLY) was introduced. Afterward, a head-to-head comparison of in vitro and in vivo experiments was performed between 99mTc-DLY and 99mTc-HYNIC-SSSLTVPWY as the monomer analog. The blocking dosage of trastuzumab reduced the uptake of the dimer about 20% more efficiently than the monomer in the SKOV-3 cell line. A twofold increase in competitive binding affinity and biological half-life was observed for 99mTc-DLY. The ovarian-tumor-bearing mice were detected with high contrast where the tumor-to-muscle ratio of 99mTc-DLY was notably increased about 40% using a gamma camera. The biodistribution experiment revealed an approximately 10% enhancement in tumor/blood, tumor/muscle, and tumor/bone ratios for the dimer. More rapid blood clearance was another achievement of the homodimer design. Overall, 99mTc-DLY successfully affected the pharmacokinetics and consequently the visualization of HER2-overexpressing tumors.

The Potential Usefulness of 99mTc-HYNIC-(Ser)3-LTVPWY Peptide for Predicting HER2 Status Alteration After Chemotherapy in Ovarian Tumor-Bearing Mice.

Purpose: The assessment of HER2 expression has a significant impact on optimizing cancer treatment protocol in patients. The aim of this study was to evaluate the potential usefulness of 99mTc-HYNIC-(Ser)3-LTVPWY peptide for detecting HER2 alteration after paclitaxel therapy of ovarian tumor xenografts in nude mice. Materials and Methods: Mice bearing SKOV-3 tumors were treated with paclitaxel and saline. The antitumor efficacy of paclitaxel was compared with the control group in tumor size and histopathological examinations. In biodistribution and imaging studies, the tumor uptakes of radiolabeled peptide were evaluated in mice-bearing ovarian tumors in both groups. The HER2 expressions in transplanted tumors were analyzed by immunohistochemistry (IHC). Results: Tumor size gradually increased in all mice during the treatment, whereas tumors had considerably faster growth in the saline group compared to those in the paclitaxel-treated mice. Paclitaxel could suppress ovarian tumor growth and prevent vascular and cell proliferation in the tumoral mass. Biodistribution and imaging results demonstrated nonsignificant radionuclide accumulations in transplanted tumors in the paclitaxel- and saline-treated groups. IHC staining confirmed the HER2 status that was similar in both groups. Conclusions: The response of HER2 status to paclitaxel in mice bearing HER2-expression tumors was profitably monitored by HER2 targeted 99mTc-HYNIC-(Ser)3-LTVPWY peptide that was agreement with IHC. The utilization of this radiolabeled peptide may be a valuable probe in evaluating HER2 status after chemotherapy.

The neglected role of Blastocystis sp. and Giardia lamblia in development of irritable bowel syndrome: A systematic review and meta-analysis.

The possible role of Blastocystis sp. and Giardia lamblia infections in the development of irritable bowel syndrome (IBS) has long been controversial. In this study, we conducted a systematic review and meta-analysis to investigate whether these protozoan infections are associated with IBS development. We systematically searched international databases for all studies that reported these protozoa in IBS patients published by May 10, 2021. Studies were included in the review if they were observational studies with confirmed patients with IBS (in case-control and cross-sectional studies) or parasitic infections (cohort studies) with an appropriate control group. Pooled odds ratios (ORs) and 95% confidence intervals were estimated using a random-effects meta-analysis model for included studies. A total of 32 papers (42 datasets), including 29 papers (31 datasets) for Blastocystis sp./IBS and 11 papers (11 datasets) for G. lamblia/IBS met the eligibility criteria. Our results indicated that the individuals with Blastocystis sp. infection were significantly at a higher risk of IBS development (OR, 1.78; 95%CI, 1.29-2.44). Moreover, cohort studies indicated a significant positive association between G. lamblia infection and IBS risk (OR, 5.47; 95%CI, 4.23-7.08); while an increasing but no statistically significant risk was observed in case-control studies (OR, 1.19; 95%CI, 0.75-1.87). Our findings suggested that Blastocystis sp. and G. lamblia infections are associated with the increased risk of developing IBS. Despite these results, further studies are needed to determine the effect of these protozoa on IBS development.

Protecting High-Risk Oncology Patients During the COVID-19 Pandemic by Creating an Isolated Outpatient Clinic.

PURPOSE: Delivering care for immunocompromised, high-risk patients with cancer during a pandemic has proven challenging. Patients with cancer on chemotherapy have a high risk of mortality if contracted COVID-19. If a patient goes directly to the emergency room, multiple contact points with other individuals can lead to unnecessary exposures from any airborne virus, such as COVID-19. Our cancer center has implemented an isolated clinic with personal protective equipment and direct access to a COVID-19 rule-out floor to manage those with febrile neutropenia (FN). METHODS: We implemented an outpatient, isolated, extended-hour clinic with access to personal protective equipment, laboratories, and antibiotics for patients with FN as a pilot project from April 1 to December 31, 2020, with the aim to decrease emergency department (ED) visits for FN by 50%. RESULTS: Since the implementation of our clinic, we have screened 74 unique patients during 102 visits, of which 76 led to a discharge and 26 led to a direct admit, thus avoiding the ED. Thirty-nine of these visits were for patients with recent travel or a known COVID-19 exposure. Bringing these patients to our isolated clinic ensured safety of the approximately 200 patients undergoing active treatment in our infusion center daily. CONCLUSION: Implementing this clinic has thus far successfully decreased the social footprint of our highest-risk patients with cancer in the ED considerably. Our efforts and hopes of decreasing the possible exposure of our immunocompromised patients to COVID-19 as well as the unnecessary exposure of the infusion center patients and personnel have thus far been effective.

The PI3K/AKT/mTOR signaling pathway inhibitors enhance radiosensitivity in cancer cell lines.

INTRODUCTION: Radiotherapy is one of the most common types of cancer treatment modalities. Radiation can affect both cancer and normal tissues, which limits the whole delivered dose. It is well documented that radiation activates phosphatidylinositol 3-kinase (PI3K) and AKT signaling pathway; hence, the inhibition of this pathway enhances the radiosensitivity of tumor cells. The mammalian target of rapamycin (mTOR) is a regulator that is involved in autophagy, cell growth, proliferation, and survival. CONCLUSION: The inhibition of mTOR as a downstream mediator of the PI3K/AKT signaling pathway represents a vital option for more effective cancer treatments. The combination of PI3K/AKT/mTOR inhibitors with radiation can increase the radiosensitivity of malignant cells to radiation by autophagy activation. Therefore, this review aims to discuss the impact of such inhibitors on the cell response to radiation.

Added diagnostic value of SPECT to evaluate bone metastases in breast cancer patients with normal whole body bone scan.

BACKGROUND: In this research, we aimed to survey the added value of single photon emission computed tomography (SPECT) in comparison with planar whole body bone scan to visualize bone metastatic lesions in patients with breast cancer. METHODS: A total of 80 patients with breast cancer (invasive ductal carcinoma) were examined with planar whole body bone scan and SPECT imaging using 99mTc-labelled methylene diphosphonate (99mTc-MDP). The patients with abnormal uptakes in SPECT imaging were also investigated with magnetic resonance imaging (MRI). RESULTS: Among these 80 patients with normal whole body bone SPECT scan, 19 (23.25%) of them revealed abnormal 99mTc-MDP uptake in skeleton. Furthermore, these 19 patients were subjected to MRI and 3 (3.75%) of them were confirmed with metastatic bone lesion. CONCLUSION: The obtained data suggest that SPECT possess the added diagnostic over planar whole body bone scan.

The pathogenic, therapeutic and diagnostic role of exosomal microRNA in the autoimmune diseases.

Exosomes are a nano-vesicle surrounded by a bilipid layer that can release from almost all cells and could be detected in tissues and biological liquids. These vesicles contain lipids, proteins, and nucleic acids (including DNA, mRNA, and miRNA) inside and on the exosomes' surface constitute their content. Exosomes can transfer their cargo into the recipient cell, which can modify recipient cells' biological activities. Recently it has been deciphering that the miRNA pattern of exosomes reveals the cellular pathophysiological situation and modifies various biological processes. Increasing data regarding exosomes highlights that the exosomes and their cargo, especially miRNAs, are implicated in the pathophysiology of various disorders, such as autoimmune disease. The current evidence on the deciphering of mechanisms in which exosomal miRNAs contributed to autoimmunity was indicated that exosomal miRNA might hold information that can reprogram the function of many of the immune cells involved in autoimmune diseases' pathogenesis. In the present study, we summarized the pathogenic role of exosomal miRNAs in several autoimmune diseases, including myasthenia gravis (MG), psoriasis, inflammatory bowel disease (IBD), type 1 diabetes (T1D), multiple sclerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's Syndrome (SS), systemic sclerosis (SSc), vitiligo, and autoimmune thyroid diseases (AITD). Moreover, in this work, we present evidence of the potential role of exosomal miRNAs as therapeutic and diagnostic agents in autoimmune diseases.

Synthesis and Biological Evaluation of 99mTc-Labeled Phenylpiperazine Derivatives as Selective Serotonin-7 Receptor Ligands for Brain Tumor Imaging.

With a poor prognosis, glioblastoma multiforme is the most aggressive tumor of the central nervous system in humans. The aim of this study was to develop novel tracers for the tumor targeting and imaging of overexpressed serotonin-7 receptors (5-HT7Rs) in U-87 MG glioma xenografted nude mice. Two phenylpiperazine derivatives named as PHH and MPHH were designed, and the corresponding radiotracers 99mTc-PHH and 99mTc-MPHH were synthesized in high radiochemical purity (>95%). 99mTc-MPHH showed a higher affinity to 5-HT7Rs on U-87 MG cells compared to 99mTc-PHH. In biodistribution studies, the radiocomplexes showed good brain uptake at 15 min combined with good radioactivity retention in the brain for 240 min. Regional rabbit brain studies indicated a higher radioactivity concentration in the hippocampus and diencephalon than in the cerebellum. Compared to 99mTc-MPHH, the 99mTc-PHH exhibited a significantly increased tumor uptake at 15 and 60 min, but the rapid blood clearance of 99mTc-MPHH led to enhanced tumor-to-muscle ratios at 240 min. A significant reduction in tumor uptake 60 min after an injection of pimozide (5-HT7 receptor antagonist) confirms the tumor uptake was receptor-mediated specifically. The tumor-to-contralateral muscle tissue ratio of 99mTc-PHH and 99mTc-MPHH in nude mice with U-87 MG xenograft was measured (5.25 and 4.65) at 60 min as well as (6.25 and 6.76) at 240 min, respectively.

Quantum-randomized polarization of laser pulses derived from zero-point diamond motion.

Intrinsic randomness in quantum systems is a vital resource for cryptography and other quantum information protocols. To date, randomizing macroscopic polarization states requires randomness from an external source, which is then used to modulate the polarization e.g. for quantum key-distribution protocols. Here, we present a Raman-based device for directly generating laser pulses with quantum-randomized polarizations. We show that crystals of diamond lattice symmetry provide a unique operating point for which the Raman gain is isotropic, so that the spontaneous symmetry breaking initiated by the quantum-random zero-point motion determines the output polarization. Experimentally measured polarizations are demonstrated to be consistent with an independent and identical uniform distribution with an estimated quantum entropy rate of 3.8 bits/pulse.