Clinicopathological significance and prognostic role of LAG3 + tumor-infiltrating lymphocytes in colorectal cancer; relationship with sidedness.

BACKGROUND: It is well-documented that the interplay between tumor-infiltrating lymphocytes (TILs) and tumor cells is a major determining factor in cancer progression. CD45RO seems to be a reliable indicator for predicting prognosis and disease outcome, along with CD3 and CD8 markers. LAG-3 is another important marker that overexpresses on TILs in a variety of cancers and is associated with disease prognosis; however, its prognostic impact is controversial. Hence, in the present study, we aimed to investigate the presence of CD45RO + , LAG3 + , CD3 + , and CD8 + lymphocytes in CRC tumor tissues and their association with clinicopathological parameters of the disease as well as patients' survival, according to primary tumor locations. METHODS: Expression of CD45RO, LAG3, CD3, and CD8 was immunohistochemically assessed in tissue sections of 136 patients with CRC. The percentages of TILs expressing these markers were then separately determined in both invasive margin (IM) and center of tumor (CT). Their associations with clinicopathological factors and patients' survival were analyzed in the entire cohort and the subgroups of patients with right- and left- rectum tumors. RESULTS: Based on our observation, CD45RO + and CD3 + cells were the most frequent infiltrated lymphocytes in both CT and IM regions of colon tumor tissue. Whilst, LAG3 + lymphocytes were the least frequent subset in both areas. Statistical analysis indicated that the frequency of CD45RO + TILs was positively associated with advanced TNM stages (III/IV), in the entire cohort and right-sided tumors (P < 0.05). LAG3 + TILs in IM were also increased in tumor tissues with higher T-stages in the entire cohort (P = 0.027). In univariate analysis, high score of CD45RO + TILs in IM was associated with better overall survival in the entire cohort. High score of CD8 + and CD45RO + lymphocytes in IM were also associated with improved survival in patients with right-sided tumors. CONCLUSIONS: Our findings generally suggest that the clinicopathological and prognostic significance of immune system-related markers such as CD45RO and LAG3 depends on the primary tumor sides. Our results collectively demonstrated that infiltration of CD45RO + lymphocytes in IM could be an independent prognostic factor in a site-dependent manner.

Effect of direct therapeutic ultrasound exposure of ovaries on histopathology, inflammatory response, and oxidative stress in dogs.

BACKGROUND: This research was designed to evaluate the effects of therapeutic ultrasound waves on ovarian germinal tissue and inflammatory cytokines (interleukin-6 (IL-6), IL1ß, tumor necrosis factor-α (TNF-α)), acute phase proteins (serum amyloid A (SAA), C reactive protein (CRP)) and oxidative stress (total antioxidant capacity (TAC), and malondialdehyde (MDA)) in dogs. Twenty-six clinically healthy adult mix-breed female dogs were aligned into three groups. Laparotomy was performed in control (n = 6) and treatment (T5, n = 10; T10, n = 10) groups. The ultrasonic exposure of ovaries in treatment groups was performed during laparotomy by round motions of the therapeutic ultrasonic transducer on both ovaries (1 MHz frequency, 1.5 W/cm2) for 5 min in the T5 group and for 10 min in the T10 group. Blood samples were collected from the jugular vein into a plain glass tube on days 0 (before laparotomy), 3, 6, and 9 after surgery. All control and treatment groups' dogs were ovariectomized for histological evaluation on day 60 after laparotomy or laparotomy + ultrasound exposure. RESULTS: Direct exposure of ovaries with therapeutic ultrasound waves induced inflammation and oxidative stress comparison with the control group. Histopathological evaluation of treated ovaries with ultrasound waves indicated a decreased number of primordial follicles (ovarian reserve) and oocyte preservation scores compared with ovaries in the control group. CONCLUSIONS: These changes may cause subfertility in the long term. It seems that inflammatory response and oxidative stress are factors in the permanent damage of ovarian tissue.

Simultaneous adrenal and retroperitoneal myelolipoma resected by laparoscopic surgery: a challenging case.

BACKGROUND: Myelolipoma is a benign neoplasm of the adrenal cortex, composed of fat and hematopoietic cells. Although myelolipoma is benign, differentiation from adrenocortical cancer may be difficult. The presence of adrenal and extra-adrenal myelolipomas simultaneously is sporadic, making it a challenging case, especially when the preoperative diagnosis is ambiguous. CASE PRESENTATION: A 65-year-old man was referred to our clinic due to a mass in the adrenal fossa. In the abdominopelvic computed tomography (CT), a well-circumscribed fat-containing 78 × 61 × 65 mm bi-lobulated mass was reported in the left adrenal fossa. The first differential diagnosis was myelolipoma. The patient was then referred to our clinic for a mass excision. He was asymptomatic and was scheduled to undergo laparoscopic-assisted adrenalectomy. After adrenalectomy and mass dissection, surprisingly, another mass was detected in the retroperitoneal area. The second mass was also dissected. The final diagnosis was myelolipoma for both masses. The patient has been symptom-free for nine months after the operation. CONCLUSION: Simultaneous adrenal and extra-adrenal myelolipoma should be considered as one of the differential diagnoses. However, because this situation is extremely rare, the probability of malignancy should be highly regarded, and we suggest an obsessive approach when approaching this condition. It is essential to manage these cases on a case-by-case basis and tailor the management concerning intraoperative biopsy, the intraoperative appearance of tumors, and the location of extra-adrenal masses.

Roles of alpha-7 nicotinic acetylcholine receptors and spleen in the lung injury induced by a repeated saline lavage in rat.

BACKGROUND: The study aimed to determine whether or notα7 nicotinic acetylcholine receptors (α7nAChR) induce anti-inflammatory effects directly in the lung or through the spleen pathway in a sterile model of lung injury by saline lavage. METHODS: Male Sprague Dawley rats were divided into seven groups; Sham, splenectomy (SPX), saline lavage (LAV), LAV treated with α7nAChR agonist nicotine (LAV + NIC), and LAV treated with NIC and a selective α7nAChR antagonist MLA (LAV+MLA+NIC), LAV and splenectomy (LAV+SPX), and LAV+SPX treated with nicotine (LAV+SPX+NIC). Tracheostomy and catheterization of the femoral artery were performed under deep anesthesia. Animals were subjected to volume-controlled ventilation and lung injury by 10 repeated saline lavages. Splenectomy was achieved one week before the induction of lung injury. The recovery phase lasted for 3 h, and drugs were injected 1 h after the last lavage. RESULTS: Mean arterial blood pressure (MBP), heart rate (HR), PaO2, PaO2/FiO2 ratio, and pH decreased, whereas, maximal inspiratory (MIP) and expiratory (MEP) pressures, and PaCO2 increased 1 h after the saline lavage. Nicotine corrected entirely all the above parameters in the LAV + NIC group. MLA or SPX prevented the effects of nicotine on the above parameters, except that MLA had no extra effect on MIP or MEP. In addition, nicotine improved lung compliance in the LAV + NIC and LAV + SPX + NIC groups, though it was inhibited by MLA in the LAV + MLA + NIC group. The increases of plasma and lung tissue malondialdehyde (MDA) in the LAV group were diminished by nicotine, whereas, MLA and SPX prevented these reductions. Besides, nicotine could reduce plasma MDA in the LAV + SPX + NIC group. Total BAL cell count, protein BAL/protein plasma ratio, and lung histological scores were attenuated by nicotine in the LAV + NIC group, whereas, MLA reversed the mentioned alterations in the LAV + MLA + NIC group. However, splenectomy could not stop the decreasing effect of nicotine on the total BAL cell in the LAV + SPX + NIC group. CONCLUSIONS: In this study, we indicated that α7nAChR and spleen play roles in cholinergic anti-inflammatory pathways in saline lavage-induced lung injury. However, our results are in favor of at least some direct effects of α 7nAChR in the lung.

Addition of carboplatin-gemcitabine as second-line neoadjuvant chemotherapy in non-responsive locally advanced breast cancer patients to standard neoadjuvant chemotherapy and evaluation of factors affecting response: a randomized controlled trial.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is the prime approach to the management of locally advanced breast cancer (LABC). Influenced by different factors such as pathologic tumor characteristics, hormone receptor status, HER2 and proliferation marker expressions, response to therapy cannot be easily predicted. Pathologic complete response (pCR) has been considered as an endpoint to NACT; however, pCR rates have been unsatisfactory in such patients. In this randomized trial, we studied the efficacy of carboplatin/gemcitabine as second-line NACT while evaluating the impact of different factors affecting response. METHODS: In this randomized controlled trial, 52 clinically non-responsive (confirmed by palpation and/or ultrasonography) LABC patients to 4 cycles of doxorubicin/cyclophosphamide followed by 4 cycles of paclitaxel ± trastuzumab were randomly allocated to two groups. "Control" group underwent breast surgery and were further evaluated for pCR (ypT0/is ypN0). "Intervention" group received 2 cycles of carboplatin/gemcitabine and patients were further evaluated for pCR following surgery. RESULTS: In a total of 52 patients, pCR rate was 30.7%. pCR and response rate in lymph nodes were higher in carboplatin/gemcitabine recipients (32% vs 29.7 and 44% vs 40.7% respectively), however differences were insignificant. In both the "intervention" group and total study population, most pCR cases were of the hormone receptor (HR)+/HER2+ subtype (87.5% and 75% respectively). HER2 positivity, ki67 expression, lower extent of ER positivity, higher tumor grade and tumor-infiltrating lymphocyte (TIL) lead to higher pCR rates. Adverse events following addition of carboplatin/gemcitabine were mostly hematologic and none required hospitalization. Anemia was the most common grade 3 adverse event observed. No grade 4 toxicity was evident. CONCLUSION: Although the proposed carboplatin/gemcitabine combination could not improve pCR rates as expected, probability of immune activation following use of carboplatin in achieving response to NACT may be considered. Accounting for the highest number of pCR cases in the "intervention" group, the HR+/HER2+ subtype with high TILs may be considered as most responsive to the proposed regimen in this study. It is noteworthy that the proposed combination imposed minimal toxicity. TRIAL REGISTRATION: This trial was prospectively registered in IRCT.ir ( IRCT2017100136491N1 ). Date of registration: 19 November 2017.

Kissing tumors; the concurrent diagnosis of leiomyosarcoma and squamous cell carcinoma of the esophagus.

BACKGROUND: Esophageal leiomyosarcoma (LMS) is a rare tumor that constitutes less than 1% of all malignant esophageal tumors. Concurrent occurrence of esophageal leiomyosarcoma with squamous cell carcinoma (SCC) is even rarer than isolated leiomyosarcoma. CASE PRESENTATION: In this report, we present a case of concurrent leiomyosarcoma and SCC in a 64-year-old woman presenting with vomiting and solid dysphagia, which has not been properly diagnosed following several referrals and diagnostic modalities. At last Exploratory laparotomy with gastric pull-up was performed in addition to radical laryngectomy with partial resection of the esophagus and subtotal thyroidectomy. Pathologic evaluation of the surgical specimen showed concurrent LMS (5.2 × 4.5 × 3 cm) and SCC (1.5 × 0.6 × 0.6 cm) at the same anatomical level in the proximal esophagus. CONCLUSIONS: This study proposes the importance of using ancillary diagnostic tests such as immunohistochemistry (IHC) to diagnose less common cases such as concurrent LMS and SCC.

Detection of Human Papillomavirus in Papillary Thyroid Carcinoma and its Association with Tumor Staging and Pathologic Features.

Background: The role of human papillomavirus (HPV), as a common infection, has been evaluated in many cancers such as the cervix and squamous cell carcinoma of the head and neck. To the best of our knowledge, for the first time, the association of HPV with papillary thyroid carcinoma (PTC) and its pathologic features are investigated. Methods: A retrospective cross-sectional study was conducted from May 2014 to January 2018 in several hospitals affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. Thyroid tissue specimens of patients diagnosed with PTC (n=82) and benign thyroid nodules (n=77) were collected using the consecutive sampling method. The presence of HPV in PTC, adjacent normal tissue, and benign thyroid nodules was evaluated using the polymerase chain reaction (PCR) method. The frequency of HPV positivity in PTC tissues was compared with benign thyroid nodules and adjacent normal tissue. Association of pathologic features of PTC with HPV positivity was also investigated. Data were analyzed using SPSS version 21.0, and P values less than 0.05 were considered statistically significant. Results: HPV PCR positivity was observed in 3.8% of benign thyroid nodules and 13.4% of PTC samples but in none of the adjacent normal tissues. After adjustment for age and sex, the prevalence of HPV PCR positivity in the PTC tissues was significantly more than the benign thyroid nodules (P=0.015). The prevalence was also significantly higher than the adjacent normal tissues (P<0.001). Conclusion: There was a significant association between PTC and HPV positivity. Further studies are required to determine the cause and effect of the association between these two conditions.

Lung injury in brain ischemia/reperfusion is exacerbated by mechanical ventilation with moderate tidal volume in rats.

Ischemic stroke is one of the most frequent causes of injury in the central nervous system which may lead to multiorgan dysfunction, including in the lung. The aim of this study was to investigate whether brain ischemia/reperfusion with or without mechanical ventilation leads to lung injury. Male Sprague-Dawley rats were assigned to four groups: Sham, 1-h brain ischemia (MCAO)/24-h reperfusion (I/R), mechanical ventilation with moderate tidal volume (MTV), and I/R+MTV. The pulmonary capillary permeability (Kfc) was measured in the isolated perfused lung. Mean arterial blood pressure (MAP), heart rate (HR), blood-gas variables, histopathological parameters, lung glutathione peroxidase, and TNF-α were measured. Kfc in the I/R, MTV, and I/R+MTV groups were higher than that in the Sham group. In the I/R, MTV, and I/R+MTV groups, arterial partial pressures of oxygen and the arterial partial pressure of oxygen/fraction of inspired oxygen ratios were lower, whereas arterial partial pressures of carbon dioxide were higher than those in the Sham group. The histopathological score in the I/R group was more than that in the Sham group, and in the MTV and I/R+MTV groups were higher than those in the Sham and I/R groups. Furthermore, there were stepwise rises in TNF-α in the I/R, MTV, and I/R+MTV groups, respectively. There was no significant difference in MAP between groups. However, HR in the MTV group was higher than that in the Sham group. Brain ischemia/reperfusion leads to pulmonary capillary endothelial damage and the impairment of gas exchange in the alveolar-capillary barrier, which is exacerbated by mechanical ventilation with moderate tidal volume partially linked to inflammatory reactions.

Impact of liver damage on blood-borne variables and pulmonary hemodynamic responses to hypoxia and hyperoxia in anesthetized rats.

BACKGROUND: Liver disorders may be associated with normal pulmonary hemodynamic, hepatopulmonary syndrome (HPS), or portopulmonary hypertension (POPH). In this study, we aimed to investigate the effect of the severity of liver dysfunctions on blood-borne variables, and pulmonary hemodynamic during repeated ventilation with hyperoxic and hypoxic gases. METHODS: Female Sprague Dawley rats were assigned into four groups of Sham (n = 7), portal vein ligation (PPVL, n = 7), common bile duct ligation (CBDL, n = 7), and combination of them (CBDL+ PPVL, n = 7). Twenty-eight days later, right ventricular systolic pressure (RVSP) and systemic blood pressure were recorded in anesthetized animals subjected to repeated maneuvers of hyperoxia (O2 50%) and hypoxia (O2 10%). Besides, we assessed blood parameters and liver histology. RESULTS: Liver histology score, liver enzymes, WBC and plasma malondialdehyde in the CBDL+PPVL group were higher than those in the CBDL group. Also, the plasma platelet level in the CBDL+PPVL group was lower than those in the other groups. On the other hand, the serum estradiol in the CBDL group was higher than that in the CBDL+PPVL group. All the above parameters in the PPVL group were similar to those in the Sham group. During ventilation with hyperoxia gas, RVSP in the CBDL+PPVL group was higher than the ones in the other groups, and in the CBDL group, it was more than those in the PPVL and Sham groups. Hypoxic pulmonary vasoconstriction (HPV) was not detected in both CBDL+PPVL and CBDL groups, whereas, it retained in the PPVL group. CONCLUSION: Severe liver damage increases RVSP in the CBDL+PPVL group linked to the high level of ROS, low levels of serum estradiol and platelets or a combination of them. Furthermore, the high RVSP at the noted group could present a reliable animal model for POPH in female rats.

Vagotomy Improves Hypoxic Pulmonary Vasoconstriction in Rats Subjected to Brain Ischemia-Reperfusion Injury.

BACKGROUND: Pulmonary dysfunction is one of the critical complications of a stroke. However, it remains unclear whether the mechanism is caused by either neurogenic or inflammatory reactions. The present study aimed to determine the effect of cerebral ischemia-reperfusion injury and the role of the vagus nerve on hypoxic pulmonary vasoconstriction (HPV) in rats. METHODS: This study was performed at Shiraz University of Medical Sciences, Shiraz, Iran, 2018. Male Sprague Dawley rats (n=56) were divided into four groups, namely the sham, vagotomy (Vag), 1 hour of ischemia followed by 23 hours of reperfusion without vagotomy (I/R) and with vagotomy (I/R+Vag). Neurological deficit scores and total infarct volumes of brains were measured in the I/R and I/R+Vag groups. Pulmonary artery pressure and lung weight were continuously registered during ventilation with normoxic and hypoxic gases in the isolated lungs. The blood gas parameters and the lung malondialdehyde (MDA) level of each group were also evaluated. ANOVA, with Tukey's post hoc test and t test, was used to compare the variables in the experimental groups. RESULTS: The infarct volume of the brains in the I/R and I/R+Vag groups were similar. HPV in the I/R group was lower than those in the sham and Vag groups, while vagotomy reversed this response in the I/R+Vag group (P=0.004). In the I/R group, PO2 and pH were lower, and PCO2 was higher than those in the sham and Vag groups. The lung MDA level in the I/R group was higher than that in the Vag group (P=0.019). CONCLUSION: Brain ischemia-reperfusion injury decreased HPV independent of increased MDA in the lung, whereas vagotomy improved HPV by repairing the blood-gas barrier and oxygen sensing.

Roles of Endothelin B Receptors and Endothelial Nitric Oxide Synthase in the Regulation of Pulmonary Hemodynamic in Cirrhotic Rats.

INTRODUCTION: Hepatopulmonary syndrome and portopulmonary hypertension are common complications of liver disorders. This study aimed to determine roles of ET-B receptors and endothelial-derived NO synthase in the regulation of pulmonary hemodynamic in cirrhotic rats. METHODS: Male Sprague-Dawley rats were divided into the Sham and common bile duct ligation (CBDL) groups. After 28 days, animals were anesthetized, and the right ventricle, femoral artery, and vein cannulated. Then, intravenous injection of BQ-788 (a selective ET-B receptor antagonist) and L-NAME (eNOS inhibitor) were performed sequentially. RESULTS: After the first injection of BQ-788, the right ventricular systolic pressure (RVSP) and mean arterial systemic pressure increased only in the Sham group. L-NAME increased RVSP in the Sham and CBDL groups, whereas mean arterial systemic pressure elevated only in the Sham group significantly. Reinjection of BQ-788 increased RVSP in the Sham group, whereas it decreased RVSP in the CBDL group. Both plasma NO metabolites and lung endothelin-1 increased in the CBDL group. CONCLUSION: ET-B receptors on the endothelial cells play roles in the regulation of pulmonary and systemic vascular tone in normal condition through the NO-mediated pathway, whereas ET-B receptors on the smooth muscle cells have a role in the pulmonary vascular tone in liver cirrhosis.

The effect of CoolClot hemostatic agent on skin wound healing in rats.

BACKGROUND: Hemostatic agents can play a key role in controlling severe hemorrhage after trauma. Previously, some criteria have been defined for improving the quality of these products; one of them is that the hemostat causes no further tissue injury. CoolClot is a recently introduced hemostatic agent that its effects on wound healing have not yet been examined, which this study aims to address. MATERIALS AND METHODS: Thirty-four adult male Sprague-Dawley rats were assigned randomly to two groups (n = 17): a study group where CoolClot hemostatic agent was applied on their wounds, and a control group whose wounds were washed only with sterile saline. The rats underwent dorsal full-thickness skin excisional wounds (20 mm diameter). On day 12 after wounding, seven rats were chosen in a random manner from each of the groups of study and control, and their skin biopsies from the wound sites were sent for histologic examination. Skin samples of the remaining rats in each group were taken on the 21st d after wound creation. Wound healing was also monitored photographically. In addition, wound surface temperature after wounding, and the application of CoolClot was recorded. RESULTS: There was no significant difference between the groups of study and control regarding the examined histopathologic parameters. The maximum increase in wound surface temperature was 1.56°C. CONCLUSIONS: One-time topical usage of CoolClot has no significant negative effect on the wound healing process. In addition, no significant increase in wound surface temperature will occur after the application of this agent.

The healing effect of bone marrow-derived stem cells in acute radiation syndrome.

OBJECTIVES: To determine the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on regeneration of bone marrow and intestinal tissue and survival rate in experimental mice with acute radiation syndrome (ARS). METHODS: Forty mice were randomly divided into two equal groups of A receiving no BMSC transplantation and B receiving BMSCs. BMSCs were isolated from the bone marrow and cultured in DMEM media. Both groups were irradiated with 10 Gy (dose rate 0.28 Gy/ min) (60)CO during 35 minutes with a field size of 35×35 for all the body area. Twenty-four hours after γ irradiation, 150×10(3) cells of passage 5 in 150 µl medium were injected intravenously into the tail. Animals were euthanized one and two weeks after cell transplantation. They were evaluated histologically for any changes in bone marrow and intestinal tissues. The survival rate in mice were also determined. RESULTS: A significant increase for bone marrow cell count and survival rate were observed in group B in comparison to group A. Histological findings denoted to a healing in sample tissues. CONCLUSION: BMSCs could significantly reduce the side effects of ARS and increase the survival rate and healing in injured tissue. As such their transplantation may open a window in treatment of patients with ARS.

Evaluation of Electrocardiogram Parameters and Heart Rate Variability During Blood Pressure Elevation by Phenylephrine in Cirrhotic Rats.

Cirrhotic cardiomyopathy is a myocardial disease that may go undetected in the early stages due to peripheral vasodilatation. The aim of the study was to evaluate the electrocardiogram (ECG) and heart rate variability (HRV) after raising blood pressure by phenylephrine injection in rats with liver cirrhosis. Twenty male Sprague-Dawley rats were divided into the Sham and common bile duct ligation (CBDL) groups. After 44 days, animals were anesthetized and the right femoral artery and vein catheterized. After a steady-state period, a bolus injection of phenylephrine (PHE, 10 µg/µl/IV, baroreflex maneuver) was followed by a slow injection of PHE (100 µg/ml/5 min/IV, sustained maneuver). Rapid and slow injections of PHE resulted in a greater increase in mean arterial pressure (MAP) and a weaker bradycardia response in the CBDL group than in the Sham group. ECG analysis showed increased QT, QTc, JT, and T peak to T end in the CBDL group, which remained unchanged after PHE injection. On the other hand, the parasympathetic indices of the HF band and RMSSD, and the sympathetic index of the LF band after PHE injection were lower in the CBDL group than in the Sham group.ECG data indicated prolonged ventricular depolarization and repolarization, independent of blood pressure levels in cirrhosis. On the other hand, after PHE injection, the parasympathetic and sympathetic components of HRV decreased, regardless of the duration of elevated blood pressure. We suggest that HRV analysis can provide a useful approach to assess cardiac dysfunction associated with elevated blood pressure in cirrhosis.

Holocord pilocytic astrocytoma in a young woman with intracranial extension: case report and review of the MRI characteristics.

INTRODUCTION: Pilocytic astrocytoma is a low-grade glioma more frequently seen in patients <20. It is pretty uncommon in the spinal cord. Rarely, astrocytoma may involve the most or total length of the spinal cord; in that case, they are called "holo-cord astrocytoma." In this case report, we are reporting the third holo-cord pilocytic astrocytoma in an adult patient and the first with an extension to the Magendie foramen. CASE PRESENTATION: We presented a 24-year-old woman with complaints of progressively worsening neck and back pain since one year ago. The patient's MRI showed a very large intradural and intramedullary cystic lesion with a solid component within the spinal cord extending from the medulla to the conus medullaris. Partial resection of the solid part of the cervical portion of the tumor was performed. Histopathological evaluation of the resected tumor segments was compatible with grade I pilocytic astrocytoma. After one year of follow-up, neck and back pain has reduced, and neurological functions have improved. CONCLUSION: Spinal cord pilocytic astrocytoma may present as a holo-cord tumor and can rarely extend to the intracranial fossa. Although this tumor does not arise from the central canal, in this case, it was extended through the Magendie foramen. Symptoms could be subtle despite extensive cord involvement. On MRI, this tumor presents as an intramedullary holo-cord cystic lesion intermixed with a solid component with a variable enhancement of the solid component.

A rare occurrence of breast, thyroid, and stomach tumors in a single patient: A case report.

INTRODUCTION AND IMPORTANCE: There are only a few case reports to date that have described patients with three or more multiple primary tumors. However, they have been reported more in the last decade, so a precise screening in patients with or without risk factors could be helpful in early diagnosis and treatment. This work has been reported in line with the SCARE criteria. CASE PRESENTATION: Here, we presented a 44-year-old female patient without any history of smoking, alcohol consumption, or cancer in her family. She had three metachronous primary tumors; breast, thyroid, and gastric cancer, which had metastasized to both her ovaries and colon. She died in January 2023 due to complex pneumonia and septic shock. To our knowledge, this article is the second case in which breast, thyroid, and stomach cancer are reported together. CLINICAL DISCUSSION: When it comes to Multiple primary malignancies (MPMs), not only screening in patients with risk factors should be considered, but patients without any other risk factors except current or past history of tumors should be screened precisely for early diagnosis and treatment. In this study, we discuss prevalence and causes of MPMs, prevalence of breast, thyroid, and stomach cancer, and also their possible relations with each other that may affect their occurrence. CONCLUSION: Reporting other cases with MPMs by physicians could lead to establish an evidence based approach to these patients.

A versatile theranostic magnetic polydopamine iron oxide NIR laser-responsive nanosystem containing doxorubicin for chemo-photothermal therapy of melanoma.

Theranostics nanoparticles (NPs) have recently received much attention in cancer imaging and treatment. This study aimed to develop a multifunctional nanosystem for the targeted delivery of photothermal and chemotherapy agents. Fe3O4 NPs were modified with polydopamine, bovine serum albumin, and loaded with DOX via a thermal-cleavable Azo linker (Fe3O4@PDA@BSA-DOX). The size of Fe3O4@PDA@BSA NPs was approximately 98 nm under the desired conditions. Because of the ability of Fe3O4 and PDA to convert light into heat, the temperature of Fe3O4@PDA@BSA NPs increased to approximately 47 °C within 10 min when exposed to an 808 nm NIR laser with a power density of 1.5 W/cm2. The heat generated by the NIR laser leads to the breaking of AZO linker and drug release. In vivo and in vitro results demonstrated that prepared NPs under laser irradiation successfully eradicated tumor cells without any significant toxicity effect. Moreover, the Fe3O4@PDA@BSA NPs exhibited the potential to function as a contrasting agent. These NPs could accumulate in tumors with the help of an external magnet, resulting in a significant enhancement in the quality of magnetic resonance imaging (MRI). The prepared novel multifunctional NPs seem to be an efficient system for imaging and combination therapy in melanoma.

Boosting wound healing in diabetic rats: The role of nicotinamide riboside and resveratrol in UPR modulation and pyroptosis inhibition.

BACKGROUND: Diabetes-related skin ulcers provide a substantial therapeutic issue, sometimes leading to amputation, needing immediate practical treatments for efficient wound care. While the exact mechanisms are unknown, pyroptosis and deregulation of the unfolded protein response (UPR) are known to exacerbate inflammation. Nicotinamide Riboside (NR) and Resveratrol (RV), which are known for their Nicotinamide adenine dinucleotide (NAD+) boosting and anti-inflammatory properties, are being studied as potential treatments. The purpose of this study was to shed light on the underlying molecular mechanisms and explore the medical application of NR and RV in diabetic wound healing. METHODS: 54 male Sprague-Dawley rats divided into control, diabetic (DM), Gel Base, DM-NR, DM-RV, and DM-NR + RV. Rats were orally administered 50 mg/kg/day of RV and 300 mg/kg/day of NR for 5 weeks. Following diabetes induction, their wounds were topically treated with 5 % NR and RV gel for 15 days. The wound closure rate, body weight, and serum lipid profiles were examined. Gene expression study evaluated UPR and pyroptosis-related genes (BIP, PERK, ATF6, IRE1α, sXBP1, CHOP, NLRP3, caspase-1, NFκB, and IL1-ß) in wound tissues, alongside histological assessment of cellular changes. RESULTS: NR and RV treatments greatly enhanced wound healing. Molecular investigation demonstrated UPR and pyroptosis marker modifications, suggesting UPR balance and anti-inflammatory effects. Histological investigation demonstrated decreased inflammation and increased re-epithelialization. The combination of NR and RV therapy had better results than either treatment alone. CONCLUSION: This study shows that NR and RV have therapeutic promise in treating diabetic wounds by addressing UPR dysregulation, and pyroptosis. The combination therapy is a viable strategy to improving the healing process, providing a multimodal intervention for diabetic skin ulcers. These findings pave the way for additional investigation and possible therapeutic applications, giving hope for better outcomes in diabetic wound care.

Prognosis of Methanol Poisoning in a Developing Setting.

BACKGROUND: Methanol-poisoning can be a challenging cause of mortality. Identifying the epidemiological, clinical, and para-clinical determinants of outcome in methanol-poisoning patients could be a step forward to its management. METHODS: In this hospital-based cohort study, 123 methanol-poisoning patients were included. Data on background variables, details of methanol consumption, and laboratory assessments were recorded for each patient. Patients underwent brain CT scans without contrast. We evaluated the association of all gathered clinical and para-clinical data with patients' outcome and length of hospital stay (LOS). Independent association of potential determinants of death, and LOS were modeled applying multivariable logistic, and Ordinary Least Square regressions, respectively. Odds ratio (OR), and regression coefficient (RC), and their 95% confidence intervals (CIs) were estimated. RESULTS: Most of the study population were male (n=107/123). The mean age of the participants was 30.3±9.1 years. Ninety patients (73.2%) were reported as being conscious on admission, and 34.3% of patients were identified with at least one abnormality in their CT scan. Level of consciousness (LOC) (OR: 42.2; 95% CI: 2.35-756.50), and blood pH (OR: 0.37; 95% CI: 0.22-0.65) were associated with death. Supratentorial edema (RC: 17.55; 95% CI: 16.95-18.16) were associated with LOS. CONCLUSION: Besides LOC, patients with any abnormality in their brain CT scan on admission were found to be at higher risk of death, and patients with supratentorial edema were at risk of longer LOS. Brain CT-scan on admission should be considered as a part of the routine procedure during the management of methanol-poisoning.

Protective and curative effects of unconjugated bilirubin on gene expression of LOX-1 and iNOS in the heart of rats receiving high-fat diet and low dose streptozotocin: a histomorphometric approach.

BACKGROUND: Atherosclerosis is a chronic inflammatory condition affecting the large arteries and is a major cause of cardiovascular diseases (CVDs) globally. Increased levels of adhesion molecules in cardiac tissue serve as prognostic markers for coronary artery occlusion risk. Given the antioxidant properties of bilirubin and its inverse correlation with atherosclerosis, this study aimed to assess the beneficial effects of bilirubin on atherosclerotic indices and heart structure in high-fat diet-fed diabetic rats with atherosclerosis. METHODS: Atherosclerosis was induced in three out of five groups of adult male Sprague Dawley rats through a 14-week period of high-fat diet (HFD) consumption and a single low dose of streptozotocin (STZ) (35 mg/kg). The atherosclerotic rats were then treated with intraperitoneal administration of 10 mg/kg/day bilirubin for either 6 or 14 weeks (treated and protected groups, respectively), or the vehicle. Two additional groups served as the control and bilirubin-treated rats. Subsequently, the mRNA expression levels of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), lectin-like LDL receptor 1 (LOX-1), and the inducible nitric oxide synthase (iNOS) were analyzed using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Histopathological and stereological analyses were performed to assess changes in the heart structure. RESULTS: Bilirubin significantly decreased the expression of VCAM-1, ICAM-1, LOX-1, and iNOS genes in the treated group. Moreover, bilirubin mitigated pathological damage in the left ventricle of the heart. Stereological analysis revealed a decrease in the left ventricle and myocardium volume, accompanied by an increase in vessel volume in rats treated with bilirubin. CONCLUSION: These findings demonstrate that mild hyperbilirubinemia can protect against the progression of atherosclerosis and heart failure by improving lipid profile, modulating adhesion molecules, LOX-1, and iNOS gene expression levels.