Fayez T. Hammad

β‐Caryophyllene (BCP), a selective agonist of cannabinoid receptor type 2 (CB2), has garnered attention as a promising nutraceutical agent for modulating organ damage. The current study aimed at evaluating the pharmacological role of BCP in Thioacetamide (TAA)‐induced liver fibrosis, with particular attention to the involvement of CB2‐mediated signaling. Following the induction of fibrosis by TAA, rats were treated with BCP for 6 weeks. In a separate group, AM630, a selective CB2 receptor antagonist, was co‐administered with BCP in order to validate CB2‐dependent actions. TAA administration triggered significant hepatocellular injury. In addition, TAA activated necroptotic cellular death, shown in the upregulated RIPK1/RIPK3/p‐MLKL expression. Growth factors' signaling was disrupted and liver regeneration was impaired. On the contrary, BCP treatment ameliorated oxidative stress, mitigated inflammation, and decreased hepatic stellate cells' activation. This was accompanied by reduced collagen deposition and attenuated fibrosis. BCP markedly abrogated necroptosis and decreased the stimulation of fibrogenic and angiogenic signaling. Additionally, BCP potentiated hepatocytes' survival and restored hepatic regenerative capacity. AM630 co‐treatment abolished BCP's protective effects, confirming the CB2 receptors‐dependent effects. Given findings highlight BCP as a potential therapeutic agent for liver fibrosis and delineate endocannabinoid system's role in modulating organ fibrosis.

Background: Preoperative anxiety (PA) is a common psychological response that can adversely affect patient satisfaction and surgical complications and outcomes. To reduce these effects, several studies were conducted to identify the factors that influence the severity of PA; however; none of the studies have examined the relationship between the PA and factors related to preoperative surgical and anesthetic counseling and the type of surgical technique. Methods: A cross-sectional questionnaire-based study was carried out between November 2023-January 2024, involving patients aged 18 years or older who were scheduled for surgical procedures at our institute. Anxiety levels were assessed using the Amsterdam Preoperative Anxiety and Information Scale (APAIS). PA was stratified into low (<11) and high (≥11) anxiety based on the total anxiety (both anesthesia- and surgery-related) scores. Results: The prevalence of clinically significant PA was 39.7%. In addition to the previously identified factors such as female gender, younger age and unemployment status, other factors which were also associated with higher PA included fewer pre-operative surgical consultations, longer duration of each surgical consultation, undergoing laparoscopic procedures instead of open surgery, referral to an internist for further evaluation of preexisting medical conditions and use of general anesthesia or uncertainty about the type of anesthesia (P < 0.05 for all). However, the number of anesthetic consultations and the surgeon’s level of experience were not significantly associated with PA. Interestingly, using illustrations and figures during consultations was also associated with higher PA (P < 0.05) while searching the internet for more information, did not have an effect. Conclusions: Preoperative anxiety remains a significant concern and was associated with factors related to gender, employment status, preoperative surgical and anesthetic counseling, surgical technique and type of anesthesia. These findings might help in formulating targeted interventions to reduce preoperative anxiety and improve surgical outcomes.

Preoperative anxiety (PA) adversely affects surgical outcomes. Compared to other surgical procedures, penile prosthesis implantation (PPI) may result in exceptionally high PA because of concerns about a foreign implant and postoperative patient's and partner's expectations, yet PA in this population has not been previously studied. This prospective cross-sectional study included all men who underwent PPI in our institute from November 2023 to November 2025. The Amsterdam Preoperative Anxiety and Information Scale (APAIS) questionnaire was used to determine the degree of PA. Participants were stratified into low (< 11) and high (≥ 11) anxiety groups based on total anxiety scores. Among 123 participants (mean age: 56.3 years), 52.8% demonstrated clinically significant PA. On univariate analysis, higher PA was associated with education level, number of previous surgical procedures, personal history of surgical or anesthetic complications, duration of surgical consultations, internet information-seeking, discussing surgery with a friend, anesthesia type, and operative duration (P < 0.05 for all). On multivariate analysis, personal history of prior surgical or anesthetic complications and internet information-seeking remained independent predictors of high PA (P < 0.05). Common concerns included device failure (25.2%), inability to activate the device (14.6%), and perceived changes in penile length, girth, or rigidity (12.2%, 9.8%, and 11.4%, respectively). PA is highly prevalent among men undergoing PPI. Prior personal history of previous surgical or anesthetic complications and internet information-seeking independently predicted high anxiety. This data might help healthcare providers to specifically target this group of patients to decrease the level of PA and its downstream consequences.

Efforts to prevent the deleterious effects of the ischemia–reperfusion injury (IRI) on the kidney are ongoing. Recently, there has been an increasing interest in using natural phytochemical compounds as alternative remedies in several diseases. Dihydromyricetin is a flavonoid that is mainly extracted from some plants such as Ampelopsis grossedentata. The effect of dihydromyricetin was investigated in a rat model of renal IRI. Dihydromyricetin was dissolved in a vehicle and administered orally as a single daily dose of 400 mg/kg for 10 days prior to IRI and continued for 3 days after IRI. G‐Sham (n = 10) underwent sham surgery, whereas G‐IRI (n = 10) and G‐IRI/DHM (n = 10) underwent bilateral warm renal ischemia for 35 min and received the vehicle or dihydromyricetin, respectively. Renal functions and histological changes were assessed before starting the medication, just prior to IRI, and 3 days after IRI. Dihydromyricetin significantly attenuated the alterations in serum creatinine and urea, creatinine clearance, urinary albumin, and urinary albumin creatinine ratio. Dihydromyricetin has also significantly mitigated the alterations in renal injury markers, pro‐inflammatory, pro‐fibrotic, and apoptotic cytokines, oxidative stress markers, and histological changes. We conclude that dihydromyricetin has a reno‐protective effect on the IRI‐induced renal alterations. These findings might have clinical implications.

Renal ischemia-reperfusion injury (IRI) is an inevitable consequence of several clinical conditions and surgical procedures including renal transplantation and resuscitation following systemic hypotension. It leads to immediate renal dysfunction and might result in long-term renal damage. Therefore, there is an ongoing effort to mitigate the deleterious effects of the IRI on the kidney. Recently, there has been a recent interest in using natural compounds as alternative remedies in many diseases. Thus, the aim of this research was to study the effect of nuciferine, a phytochemical compound extracted from the plant Nelumbo nucifera Gaertn, on the renal dysfunction in a rat mode of IRI. Nuciferine was administered orally as single daily dose of 30 mg/kg for 9 days prior to IRI and continued for 3 days post-IRI. G-Sham (n = 11) underwent sham surgery whereas G-IRI (n = 12) and G-IRI/NF (n = 12) underwent bilateral warm renal ischemia for 35 minutes. G-IRI/NF received nuciferine. Renal functions and histological changes were assessed before starting the medication, just prior to IRI and 3 days after IRI. Nuciferine significantly attenuated the alterations in serum creatinine, serum urea, creatinine clearance and urinary albumin creatinine ratio. This was associated with significant attenuation of the alterations in renal injury markers, several cytokines including pro-inflammatory, pro-fibrotic and apoptotic cytokines and in histological changes. In conclusion, nuciferine has reno-protective effects on the IRI-induced renal dysfunction. These findings might be of clinical significance.

Background/Objectives: Obstructive uropathy is a common cause of renal impairment. Recently, there has been a burgeoning interest in exploring natural products as potential alternative remedies for many conditions due to their low toxicity, affordability and wide availability. Methods: We investigated the effect of nerolidol in a rat model of bilateral ureteral obstruction (BUO) injury. Nerolidol, dissolved in a vehicle, was administered orally as a single daily dose of 200 mg/kg to Wistar rats. Sham group (n = 12) underwent sham surgery, whereas the BUO (n = 12) and BUO/NR groups (n = 12) underwent reversible 24-h BUO and received the vehicle or nerolidol, respectively. The treatment started 9 days prior to the BUO/sham surgery and continued for 3 days after reversal. Renal functions were assessed before starting the treatment, just prior to the intervention and 3 days after BUO reversal. Results: Neither nerolidol nor the vehicle affected the basal renal functions. Nerolidol resulted in a significant attenuation in the BUO-induced alterations in renal functional parameters such as serum creatinine and urea, creatinine clearance and urinary albumin-creatinine ratio. Nerolidol also attenuated the changes in several markers associated with renal injury, inflammation, apoptosis and oxidative stress and mitigated the histological alterations. Conclusions: The findings of this study demonstrated the potent reno-protective effects of nerolidol in mitigating the adverse renal effects of bilateral ureteral obstruction. This is attributed to its anti-inflammatory, anti-fibrotic, anti-apoptotic and anti-oxidant properties. These effects were reflected in the partial recovery of renal functions and histological features. These findings may have potential therapeutic implications.

Research has demonstrated that hypertension can lead to an exaggeration in the renal functional and histological changes caused by ureteral obstruction. These changes were particularly observed shortly after the release of a relatively brief period of unilateral ureteral obstruction (UUO). However, the long-term impact of hypertension on the recovery of renal functions has not been investigated beyond the immediate period after UUO reversal. In order to investigate this effect, a group of spontaneously hypertensive rats (G-SHR, n = 11) and a group of normotensive Wistar Kyoto rats (G-NTR, n = 11) were subjected to a 48 h reversible left UUO. The impact of UUO was then examined 45 days after the reversal of obstruction. The glomerular filtration rate, renal blood flow, and the fractional excretion of sodium in the post-obstructed left kidney (POK) showed similarities to the non-obstructed right kidney (NOK) in both groups. However, the changes in the albumin creatinine ratio, renal injury markers, pro-apoptotic markers, and histological changes in the G-SHR were much more pronounced compared to the G-NTR. We conclude that hypertension continues to have a significant impact on various aspects of renal injury and function, even several weeks after UUO reversal.

Both ureteral obstruction (UO) and hypertension are common conditions that affect kidney functions. Hypertension and chronic kidney disease are closely associated with an overlapping and intermingled cause-and-effect relationship. The effect of hypertension on the renal dysfunction following reversible UO has not been studied previously. To study this effect, spontaneously hypertensive (G-HT, n = 10) and normotensive Wistar (G-NT, n = 10) rats underwent 48-h reversible left unilateral UO (UUO), and the effect of UUO was studied 96 h following UUO reversal. The glomerular filtration rate, renal blood flow, and renal tubular functions such as the fractional excretion of sodium in the post-obstructed left kidney (POK) in both groups were significantly altered compared with the non-obstructed right kidney (NOK). However, the alterations in the G-HT were significantly more exaggerated when compared with the G-NT. Similar findings were observed with the histological features, gene expression of kidney injury markers, pro-inflammatory, pro-fibrotic and pro-apoptotic cytokines, and pro-collagen, as well as tissue levels of apoptotic markers. We conclude that hypertension has significantly exaggerated the alterations in renal functions and other parameters of renal injury associated with UUO.

Efforts to decrease the deleterious effects of renal ischemia–reperfusion injury (IRI) are ongoing. Recently, there has been increasing interest in using natural phytochemical compounds as alternative remedies in several diseases. Nerolidol is a natural product extracted from plants with floral odors and has been proven to be effective for the treatment of some conditions. We investigated the effect of nerolidol in a rat model of renal IRI. Nerolidol was dissolved in a vehicle and administered orally as single daily dose of 200 mg/kg for 5 days prior to IRI and continued for 3 days post IRI. G-Sham (n = 10) underwent sham surgery, whereas G-IRI (n = 10) and G-IRI/NR (n = 10) underwent bilateral warm renal ischemia for 30 min and received the vehicle/nerolidol, respectively. Renal functions and histological changes were assessed before starting the medication, just prior to IRI and 3 days after IRI. Nerolidol significantly attenuated the alterations in serum creatinine and urea, creatinine clearance, urinary albumin and the urinary albumin–creatinine ratio. Nerolidol also significantly attenuated the alterations in markers of kidney injury; proinflammatory, profibrotic and apoptotic cytokines; oxidative stress markers; and histological changes. We conclude that nerolidol has a renoprotective effect on IRI-induced renal dysfunction. These findings might have clinical implications.